title: 2018 World Series

text: Game 2 featured another matchup of left-handed pitchers; Boston started David Price, who got the win in Game 5 of the 2018 American League Championship Series, while Los Angeles started Hyun-jin Ryu, who took the loss in Game 6 of the 2018 National League Championship Series. The Red Sox again scored first, this time in the second inning, when Xander Bogaerts doubled and then scored on a single by Ian Kinsler. The Dodgers loaded the bases in the fourth inning and David Freese scored on a sacrifice fly by Matt Kemp to tie the game; Yasiel Puig then singled to drive in Manny Machado with the go-ahead run. After the Red Sox loaded the bases against Ryu in the bottom of the fifth, reliever Ryan Madson walked in the tying run and J. D. Martinez drove in two more with a single. Ryu's final line was four runs allowed on six hits and one walk with five strikeouts in 4 innings.


title: 2018 World Series

text: Price only allowed two runs on three hits and three walks in six innings while striking out five. Both bullpens prevented more runs from scoring as the Red Sox won, 4–2, to take a two games to none lead. Ryu took the loss for the Dodgers, while Price earned the win for Boston with closer Craig Kimbrel getting his sixth save this postseason. It was also the 100th postseason victory in Red Sox franchise history.


title: 2018 World Series

text: After two games started by left-handed pitchers, both teams started right-handed pitchers for Game 3; Walker Buehler for the Dodgers and Rick Porcello for the Red Sox. With no designated hitter, J. D. Martinez started in left field for the Red Sox, in place of usual left fielder Andrew Benintendi. The Dodgers scored first, for the first time in the series, when Joc Pederson homered in the third inning. Porcello pitched 4 innings, allowing the one run on three hits and one walk while striking out five. Buehler pitched seven scoreless innings allowing only two hits with no walks and seven strikeouts. Jackie Bradley Jr. hit a home run off Kenley Jansen with two outs in the eighth inning to tie the game. It was Jansen's first blown save in four opportunities this postseason.


title: 2018 World Series

text: No one scored in the ninth after Cody Bellinger was caught between bases to end the ninth and the game went into extra innings tied at one. In the top of the 10th inning, pinch-runner Ian Kinsler attempted to score from third on Rafael Devers's sacrifice fly, but a strong throw by center fielder Bellinger had Kinsler out at the plate. In the 13th inning, Brock Holt walked, advanced on a wild pitch and scored the go-ahead run on an infield single by Eduardo Núñez and a throwing error by pitcher Scott Alexander. Then in the bottom of the inning, Max Muncy walked against Nathan Eovaldi, advanced to second on a pop out to Núñez in foul territory (Nuñez made a great catch and tumbled into the stands after making the catch, which allowed Muncy to advance) and then scored the tying run after an infield hit by Yasiel Puig and a throwing error by Ian Kinsler. In the bottom of the 15th, Muncy appeared to hit a walk-off home run down the right-field line but the ball hooked foul. Muncy hit a walk-off home run off Eovaldi in the 18th inning to win it for the Dodgers, 3–2, to cut their series deficit to 2–1. Eovaldi had just begun his seventh inning of relief.


title: 2018 World Series

text: At 18 innings and seven hours and 20 minutes, this contest became the longest World Series game by both innings and time, surpassing (in playing time) Game 3 of the 2005 World Series, which lasted 14 innings and five hours and 41 minutes, and breaking the record (in innings) first set in Game 2 of the 1916 World Series, when the Red Sox and Dodgers (then known as the Robins) played 14 innings.


title: 2018 World Series

text: Muncy tied the record for latest (18th inning) walk-off hit in postseason history, equalling Chris Burke in Game 4 of the 2005 National League Division Series. It was also the Dodgers' first game-winning World Series home run since Kirk Gibson in Game 1 of the 1988 World Series. The game took longer to play than the entire 1939 World Series, which had seven hours and five minutes of total playing time over four games. Until Game 1 of the 2020 World Series, this was the last time a team won a World Series game in their home ballpark.


title: 2018 World Series

text: Following the longest game in World Series history, the Dodgers started Rich Hill while Eduardo Rodríguez made his first start of the postseason for the Red Sox. At 38 years old, Hill was the oldest player to start a World Series game since 39-year-old Tim Hudson started two games for the San Francisco Giants in 2014 and the oldest for the Dodgers since Sal Maglie in 1956. As he had pitched in relief in Game 3, Rodríguez became just the sixth pitcher in history to start a World Series game with zero days rest, and the first since Firpo Marberry of the Washington Senators in the 1924 World Series. The Red Sox had intended to start Nathan Eovaldi, but he needed rest after throwing 97 pitches in relief in Game 3. With no designated hitter, the Red Sox started an outfield of Andrew Benintendi, Mookie Betts, and J. D. Martinez, with Jackie Bradley Jr. on the bench in place of Benintendi, who did not start the previous game.


title: 2018 World Series

text: The game was scoreless through the first five innings. In the bottom of the sixth, the Dodgers loaded the bases against Rodríguez and scored the game's first run on a throwing error by catcher Christian Vázquez. The next batter, Yasiel Puig, hit a three-run home run to extend the lead to 4–0. In a fit of rage, Rodríguez slammed his glove down on the mound in frustration and was later pulled after pitching 5 innings, allowing the four runs on four hits and two walks with six strikeouts. At that point, Red Sox ace Chris Sale made an angry speech that fired up his teammates in the dugout. In the top of the seventh, after striking out Eduardo Núñez with a runner on first, Hill was taken off the mound in favor of reliever Ryan Madson, a decision by Roberts which was criticized by several including then-current President Donald Trump. Mitch Moreland hit a three-run pinch-hit home run off of Madson to make it a one-run game. Hill was charged with one run in innings on one hit and three walks with seven strikeouts. Madson set a new World Series record by allowing seven inherited runners to score in the series. Steve Pearce hit a homer off Kenley Jansen in the eighth inning. This was the second straight day Jansen allowed a game-tying home run in that inning.


title: 2018 World Series

text: Jansen became just the second pitcher in World Series history to allow game-tying home runs in back-to-back games (Byung-hyun Kim for the Arizona Diamondbacks in 2001 was the other). In the top of the ninth, Brock Holt doubled off Dylan Floro and was driven in by a single by pinch hitter Rafael Devers to give Boston their first lead of the game. The Red Sox loaded the bases against Floro and Alex Wood and then Pearce doubled to right-center off Kenta Maeda, scoring all three base runners to put the Red Sox up, 8–4. They added another run when Xander Bogaerts drove in Pearce with a single. Kiké Hernández hit a two-run homer off of Craig Kimbrel in the ninth to cut the lead to three. Kimbrel was able to get the last three outs and the Red Sox took a three games to one lead.


title: 2018 World Series

text: On October 28, Los Angeles became the first city to host an MLB, NFL (Rams), NBA (Clippers), NHL (Kings), and MLS (Galaxy) game all on the same day. Clayton Kershaw started for the Dodgers, while David Price started for the Red Sox. Price became the first pitcher to start World Series games no more than four days apart while also pitching in relief between those games since Jack Billingham of the Cincinnati Reds did so in the 1972 World Series. Jackie Bradley Jr. again did not start in the outfield for Boston, but entered the game as a defensive replacement in the bottom of the ninth inning.


title: 2018 World Series

text: Both teams scored in the first inning. The Red Sox scored in the top of the inning after a one out single by Andrew Benintendi followed by a two-run home run by Steve Pearce. David Freese led off the bottom of the inning with a home run for the Dodgers. No one else scored until the sixth inning, when Mookie Betts hit a home run with one out and then J. D. Martinez hit a lead-off homer in the seventh to make it 4–1. Kershaw pitched seven innings, allowing four runs on seven hits, with five strikeouts and no walks.


title: 2018 World Series

text: In the eighth inning, Pearce hit another home run, this time off of Pedro Báez. Price pitched into the eighth, allowing only one run on three hits and two walks while striking out five. He became just the fifth pitcher to pitch 6+ innings and allow three or fewer hits in three straight postseason starts. Joe Kelly and Chris Sale pitched the last two innings and both struck out the side, Sale getting Manny Machado to strike out for the last out, the Red Sox winning the game 5–1 and the title 4–1. Pearce won the World Series Most Valuable Player Award.


title: 2018 World Series

text: The World Series was televised nationally by Fox for the 19th straight year. Joe Buck was the play-by-play announcer, with John Smoltz as the color commentator. Ken Rosenthal and Tom Verducci were the field reporters. Fox Deportes offered a Spanish-language feed, with Rolando Nichols providing play-by-play and Carlos Álvarez and Edgar Gonzalez doing color commentary.


title: 2018 World Series

text: Outside of the United States, MLB International carried the series with play-by-play by Matt Vasgersian and color commentary by Buck Martinez.


title: 2018 World Series

text: ESPN Radio broadcast all the World Series games in English for the 21st straight year as part of "Major League Baseball on ESPN Radio". Dan Shulman called the play-by-play, with Chris Singleton serving as color analyst and Buster Olney as field reporter. Marc Kestecher hosted the pre-game show with Olney and Tim Kurkjian reporting. Jon Sciambi called the play-by-play for Game 5 due to Shulman developing laryngitis.


title: 2018 World Series

text: ESPN Deportes Radio provided Spanish-language coverage of the Series. Eduardo Ortega called the play-by-play and Orlando Hernández, Renato Bermudez, and José Francisco Rivera served as analysts.


title: 2018 World Series

text: Locally, both teams' flagship radio stations broadcast the series with their regular announcers, which were simulcast over SiriusXM radio. In Los Angeles, the broadcast was on AM 570 LA Sports with Charley Steiner and Rick Monday in English, on Univision America 1020 with Jaime Jarrín and Jorge Jarrín in Spanish, and on Radio Korea 1540 AM in Korean. The Red Sox broadcast was on WEEI 93.7 FM in English with Joe Castiglione, Tim Neverett and Lou Merloni, and in Spanish on WCCM 1490 AM with Uri Berenguer.


title: 2018 World Series

text: The 2018 World Series was sponsored by YouTube TV, the second consecutive year that the service sponsored the series. This sponsorship included logo branding in-stadium and on official digital properties, on the field, as well as commercial inventory during Fox's telecasts of the games. As part of the agreement, YouTube TV would later sponsor the 2019 World Series.


title: 2018 World Series

text: On the morning of October 31, the Red Sox celebration parade began at Fenway Park and made its way downtown to its final destination on Staniford Street. During the celebration, the World Series trophy sustained minor damage from a beer can thrown by a spectator; it was subsequently repaired.


title: 2018 World Series

text: An 80-minute documentary, "2018 World Series: Damage Done", which was produced by MLB and narrated by Uzo Aduba, was released on December 4.


title: 2018 World Series

text: On December 3, Red Sox president Sam Kennedy announced that team accepted an invitation to visit the White House. Originally planned for February 15, 2019, the visit was postponed to May 9, 2019, due to the 2018–19 United States federal government shutdown. Alex Cora announced that he would not attend, citing the administration's response to Hurricane Maria in his native Puerto Rico. On May 9, various team members along with owner John W. Henry and president of baseball operations Dave Dombrowski visited the White House and met with President Trump.


title: 2018 World Series

text: During the 2018–2019 off-season, the Dodgers signed former Red Sox reliever Joe Kelly to a three-year deal. Kelly was marvelous in the World Series against the Dodgers, having struck out ten batters and not allowing a run in five games pitched. Kelly, an Angels fan who disliked the Dodgers growing up in Corona, became a fan favorite with Dodger fans throughout his tenure with the team.


title: 2018 World Series

text: Four months after the 2018 World Series, the Patriots won Super Bowl LIII, meaning the greater Boston area celebrated multiple championships for the 2018 MLB and NFL seasons. Greater Boston accomplished feat 14 years previously when the Red Sox won their first World Series in 86 years, while the Patriots won their third Super Bowl in four years. Like the ‘18 Red Sox, the Patriots beat a Los Angeles team (the Rams) in the Championship Game.


title: 2018 World Series

text: The 2018 World Series would be the peak for the 2016–2018 Red Sox, who were the first Red Sox teams in franchise history to win the American League East for three straight seasons. President of Baseball Operations Dave Dombrowski was fired on September 9, 2019, just 10 months after winning the 2018 World Series. On the field, Boston's top three starters in 2018 — Chris Sale, David Price, and Nathan Eovaldi — all missed significant time due to injury in 2019. Overall, the Red Sox would finish 19 games behind the AL East-leading Yankees in 2019.


title: 2018 World Series

text: Three significant events happened to the Red Sox before the start of the 2020 season that shaped the course of the team's future:


title: 2018 World Series

text: The Red Sox would finish the COVID-19-shortened 2020 season 24–36 (.400 winning percentage), which was their worst season since 1965. The team would rebound in 2021 and make it all the way to the ALCS before eventually losing to the Houston Astros in six games.


title: 2018 World Series

text: Corey Seager returned to the Dodgers after being out for most of the 2018 season due to an elbow injury, while Manny Machado, who replaced him after the All-Star break, signed a record free agent contract with the San Diego Padres. The 2019 Dodgers broke the franchise record for wins at 106, but would experience October heartbreak once again by losing to eventual World Champion Washington Nationals in the NLDS in five games. The Dodgers became the second franchise to lose to the eventual World Series champions in four consecutive postseasons (the New York Yankees from 2001 to 2004 were the first).


title: 2018 World Series

text: The Dodgers traded for Mookie Betts during the 2019-2020 off-season and his addition made a great team even better. The Dodgers in 2020 would set the record for best winning percentage in franchise history (.717), win their 8th straight division title, and their first World Series in 32 years.


title: International cricket in 2022

text: The 2022 international cricket season was from May 2022 to September 2022. 15 Tests, 68 One Day Internationals (ODIs), and 54 Twenty20 Internationals (T20Is) matches, including the 2022 Asia Cup, were played in this season. In women's international cricket 18 Women's One Day Internationals (WODIs), 40 Women's Twenty20 Internationals (WT20Is), and a women's Test match were scheduled to be held in this season. Additionally, a number of other T20I/WT20I matches were played in series involving associate nations.


title: International cricket in 2022

text: In May 2022, the International Cricket Council (ICC) confirmed that the third cycle of the ICC Women's Championship would start during this season, with the Pakistan women's team hosting Sri Lanka in June 2022. At the same time, the ICC also awarded WODI status to the Netherlands, Papua New Guinea, Scotland, Thailand and the United States. Also in women's international cricket, a tournament was held as part of the 2022 Commonwealth Games, in Birmingham, England, in July and August 2022.


title: International cricket in 2022

text: In September 2021, the fifth Test match between England and India was cancelled a few hours before the scheduled start, due to COVID-19 cases in the Indian camp. The match was rescheduled, and took place in July 2022, ahead of India's white-ball tour of England. In July 2022, Cambodia, the Ivory Coast and Uzbekistan were all awarded Associate Membership of the ICC.


title: Veblen good

text: A Veblen good is a type of luxury good for which the demand increases as the price increases, in apparent (but not actual) contradiction of the law of demand, resulting in an upward-sloping demand curve. The higher prices of Veblen goods may make them desirable as a status symbol in the practices of conspicuous consumption and conspicuous leisure. A product may be a Veblen good because it is a positional good, something few others can own.


title: Veblen good

text: Veblen goods are named after American economist Thorstein Veblen, who first identified conspicuous consumption as a mode of status-seeking (i.e., keeping up with the Joneses) in "The Theory of the Leisure Class" (1899). The testability of this theory was questioned by Colin Campbell due to the lack of complete honesty from research participants. However, research in 2007 studying the effect of social comparison on human brains can be used as an evidence supporting Veblen. The idea that seeking status can be an incentive to spend was also later discussed by Fred Hirsch.


title: Veblen good

text: Additionally, there have been different arguments on whether Veblen’s theory applies only to luxury goods or all goods.


title: Veblen good

text: A corollary of the Veblen effect is that lowering the price may increase the demand at first, but will decrease the quantity demanded afterwards.


title: Veblen good

text: The theory of Veblen good made a significant contribution towards marketing and advertising. There are multiple studies considering Veblen goods as a tool to develop and maintain a strong relationship with consumers.


title: Veblen good

text: While Veblen goods are more affordable for high income households and affluent societies are usually known as the targeted income groups of Veblen brands, they have been experiencing a trend away from conspicuous consumption.


title: Veblen good

text: Despite what appears to be a violation of the law of demand, the upward-sloping demand curve for a Veblen good does not actually violate the Law. This is because the good's social value depends on the price; in other words, the good itself changes as the price changes. This is illustrated when looking at the derivative of societal demand for a social good (goods whose value depends on others' consumption of it) with respect to price:


title: Veblen good

text: In other words, the rise in price increases the societal demand for the good. Because an individual demands less of this good the more others have, the entire left-hand side is positive, meaning the right-hand side is positive. The RHS means that, in general, people will demand more of the social good as the higher price goes (though not necessarily every individual will do so). Because the price itself leads to a change in the social good's value, as opposed to a pure price effect leading to an increase in demand, this does not constitute a law of demand violation.


title: Veblen good

text: Being aware of the existence of Veblen goods, concerns were raised regarding their wastefulness as they are viewed as deadweight loss. Consuming Veblen goods also results in other financial and social consequences such as conspicuous demonstration of unequal wealth distribution and the need to adjust tax formulas. Another negative outcome is that this type of consumption can be a culprit of the future exacerbation of pollution.


title: Veblen good

text: Nonetheless, one exception is ethical consumers interested in virtue signaling through their consumption of goods and services. Veblen goods targeting this market segment must also be ethically manufactured to increase in their quantity demanded.


title: Veblen good

text: The Veblen effect is one of a family of theoretical anomalies in the general law of demand in microeconomics. Related effects include:


title: Veblen good

text: Sometimes, the value of a good increases as the number of buyers or users increases. This is called the bandwagon effect when it depends on the psychology of buying a product because it seems popular, or the network effect when a large number of buyers or users itself increases the value of a good. For example, as the number of people with telephones or Facebook accounts increased, the value of having a telephone or Facebook account increased because the user could reach more people. However, neither of these effects suggests that raising the price would boost demand at a given level of saturation.


title: Veblen good

text: Some of these effects are discussed in a 1950 article by economist Harvey Leibenstein. Counter-examples have been called the counter-Veblen effect.


title: Veblen good

text: The effect on demand depends on the range of other goods available, their prices, and whether they serve as substitutes for the goods in question. The effects are anomalies within demand theory, because the theory normally assumes that preferences are independent of price or the number of units being sold. They are therefore collectively referred to as "interaction effects".


title: Veblen good

text: Interaction effects are a different kind of anomaly from that posed by Giffen goods. The Giffen goods theory is one for which observed quantity demanded rises as price rises. Still, the effect arises without any interaction between price and preference—it results from the interplay of the "income effect" and the "substitution effect" of a price change.


title: Nuclear testing at Bikini Atoll

text: Nuclear testing at Bikini Atoll consisted of the detonation of 23 nuclear weapons by the United States between 1946 and 1958 on Bikini Atoll in the Marshall Islands. Tests occurred at 7 test sites on the reef itself, on the sea, in the air, and underwater. The test weapons produced a combined fission yield of 42.2 Mt of TNT in explosive power.


title: Nuclear testing at Bikini Atoll

text: The United States and its allies were engaged in a Cold War nuclear arms race with the Soviet Union to build more advanced bombs from 1947 until 1991. The first series of tests over Bikini Atoll in July 1946 was codenamed Operation Crossroads. "Able" was dropped from an aircraft and detonated above the target fleet. The second, "Baker", was suspended under a barge. It produced a large Wilson cloud and contaminated all of the target ships. Chemist Glenn T. Seaborg, the longest-serving chairman of the Atomic Energy Commission, called the second test "the world's first nuclear disaster."


title: Nuclear testing at Bikini Atoll

text: The second series of tests in 1954 was codenamed Operation Castle. The first detonation was Castle Bravo, which tested a new design utilizing a dry-fuel thermonuclear bomb. It was detonated at dawn on March 1, 1954. Scientists miscalculated: the 15 Mt of TNT nuclear explosion far exceeded the expected yield of 4–8 Mt of TNT (6 predicted). This was about 1,000 times more powerful than either of the atomic bombs dropped on Hiroshima and Nagasaki during World War II. The scientists and military authorities were shocked by the size of the explosion, and many of the instruments that they had put in place to evaluate the effectiveness of the weapon were destroyed.


title: Nuclear testing at Bikini Atoll

text: Authorities had promised the Bikini Atoll's residents that they would be able to return home after the nuclear tests. A majority of the island's family heads agreed to leave the island, and most of the residents were moved to the Rongerik Atoll and later to Kili Island. Both locations proved unsuitable to sustaining life, and the United States had to provide residents with on-going aid. Despite the promises made by authorities, these and further nuclear tests (Redwing in 1956 and Hardtack in 1958) rendered Bikini unfit for habitation, contaminating the soil and water, making subsistence farming and fishing too dangerous. The United States later paid the islanders and their descendants $125 million in compensation for damage caused by the nuclear testing program and their displacement from their home island. A 2016 investigation found radiation levels on Bikini Atoll as high as 639 mrem yr (6.39mSv/a), well above the established safety standard for habitation. However, Stanford University scientists reported "an abundance of marine life apparently thriving in the crater of Bikini Atoll" in 2017.


title: Nuclear testing at Bikini Atoll

text: In February 1946, the United States government forced the 167 Micronesian inhabitants of the atoll to temporarily relocate so that testing could begin on atomic bombs. King Juda agreed to the request, announcing that "we will go believing that everything is in the hands of God." Nine of the eleven family heads chose Rongerik as their new home. Navy Seabees helped them to disassemble their church and community house and prepare to relocate to their new home. On March 7, 1946, the residents gathered their belongings and building supplies. They were transported eastward on Navy landing craft 1108 and LST 861 to the uninhabited Rongerik Atoll, which was one-sixth the size of Bikini Atoll. No one lived on Rongerik because it had an inadequate water and food supply, and also due to traditional beliefs that the island was haunted by the "Demon Girls of Ujae". The Navy left them with a few weeks of food and water which soon proved inadequate.


title: Nuclear testing at Bikini Atoll

text: The United States assembled a support fleet of 242 ships that provided quarters, experimental stations, and workshops for more than 42,000 personnel. The islands were primarily used as recreation and instrumentation sites. Seabees built bunkers, floating dry docks, steel towers for cameras and recording instruments, and other facilities on the island to support the servicemen. These included the "Up and Atom Officer's Club" and the "Cross Spikes Club", a bar and hang-out created by servicemen on Bikini Island between June and September 1946. The "club" was little more than a small open-air building which served alcohol to servicemen and provided outdoor entertainment, including a ping pong table. The "Cross Spikes Club" was the only entertainment that the enlisted servicemen had access to during their June to September stay at Bikini.


title: Nuclear testing at Bikini Atoll

text: The Navy designated Bikini Atoll lagoon as a ship graveyard, then brought in 95 ships, including carriers, battleships, cruisers, destroyers, submarines, attack transports, and landing ships. The proxy fleet would have comprised the sixth largest naval fleet in the world if the ships had been active. All carried varying amounts of fuel, and some carried live ordnance.


title: Nuclear testing at Bikini Atoll

text: Crossroads consisted of two detonations, each with a yield of 23 kt of TNT (96 TJ). "Able" was detonated over Bikini on July 1, 1946 and exploded at an altitude of , but was dropped by aircraft about off target. It sank only five of the ships in the lagoon. "Baker" was detonated underwater at a depth of on July 25, sinking eight ships. The second underwater blast created a large condensation cloud and contaminated the ships with more radioactive water than was expected. Many of the surviving ships were too contaminated to be used again for testing and were sunk. The air-borne nuclear detonation raised the surface seawater temperature by , created blast waves with speeds of up to , and shock and surface waves up to high. Blast columns reached the floor of the lagoon, which is approximately deep.


title: Nuclear testing at Bikini Atoll

text: "Charlie" was planned for 1947 but was canceled primarily because of the Navy's inability to decontaminate the target ships after the "Baker" test. "Charlie" was rescheduled as Operation Wigwam, a deep water shot conducted in 1955 off the California coast.


title: Nuclear testing at Bikini Atoll

text: The next series of tests over Bikini Atoll was codenamed Operation Castle. The first test of that series was Castle Bravo, a new design utilizing a dry fuel thermonuclear bomb. It was detonated at dawn on March 1, 1954.


title: Nuclear testing at Bikini Atoll

text: The explosion yielded 15 Mt of TNT, far exceeding the expected yield of 4 to 8 Mt of TNT (6 predicted), and was about 1,000 times more powerful than each of the atomic bombs dropped on Hiroshima and Nagasaki during World War II. The device was the most powerful nuclear weapon ever detonated by the United States and just under one-third the energy of the Tsar Bomba, the largest nuclear device ever tested. The scientists and military authorities were shocked by the size of the explosion, and it destroyed many of the instruments put in place to evaluate the effectiveness of the test.


title: Nuclear testing at Bikini Atoll

text: The unexpectedly large yield led to the most significant radiological contamination caused by the United States. A few minutes after the detonation, blast debris began to fall on Eneu/Enyu Island on Bikini Atoll where the crew who fired the device were located. Their Geiger counters detected the unexpected fallout, and they were forced to take shelter indoors for a number of hours before it was safe for an airlift rescue operation.


title: Nuclear testing at Bikini Atoll

text: The fallout continued to spread across the inhabited islands of the Rongelap, Rongerik, and Utrik Atolls. The inhabitants of Rongelap and Rongerik Atolls were evacuated by servicemen two days after the detonation, but the residents of the more distant Utrik Atoll were not evacuated for three days. Many of them soon began to show symptoms of acute radiation syndrome. They returned to the islands three years later but were forced to relocate again when the islands were found to be unsafe.


title: Nuclear testing at Bikini Atoll

text: The fallout gradually dispersed around the globe, depositing traces of radioactive material in Australia, India, Japan, and parts of the United States of America and Europe. It had been organized as a secret test, but Castle Bravo quickly became an international incident prompting calls for a ban on atmospheric testing of thermonuclear weapons.


title: Nuclear testing at Bikini Atoll

text: The Rongelap Atoll was coated with up to of snow-like irradiated calcium debris and ash over the entire island. Virtually all the inhabitants experienced severe radiation sickness, including itchiness, sore skin, vomiting, diarrhea, and fatigue. Their symptoms also included burning eyes and swelling of the neck, arms, and legs. They were forced to abandon the islands three days after the tests, leaving behind all their belongings. The U.S. government relocated them to Kwajalein for medical treatment.


title: Nuclear testing at Bikini Atoll

text: Six days after the Castle Bravo test, the government set up a secret project to study the medical effects of the weapon on the residents of the Marshall Islands. The United States was subsequently accused of using the inhabitants as medical research subjects without obtaining their consent to study the effects of nuclear exposure. Until that time, the Atomic Energy Commission had given little thought to the potential impact of widespread fallout contamination and health and ecological impacts beyond the formally designated boundary of the test site.


title: Nuclear testing at Bikini Atoll

text: Ninety minutes after the detonation, 23 crew members of the Japanese fishing boat the "Daigo Fukuryū Maru" ("Lucky Dragon No. 5") were contaminated by the snow-like irradiated debris and ash. They had no idea what the explosion was and no understanding of the debris that rained down like snow, but they all soon became ill with the effects of acute radiation sickness. One fisherman died about six months later while under doctor supervision; his cause of death was ruled a pre-existing liver cirrhosis compounded by a hepatitis C infection. The majority of medical experts believe that the crew members were infected with hepatitis C through blood transfusions during part of their acute radiation syndrome treatment.


title: Nuclear testing at Bikini Atoll

text: Edward Teller was one of the driving minds behind the development of the hydrogen bomb and an architect of the Marshall Island tests. After the mass media painted the fisherman's death as an anti-nuclear call to arms, Teller notoriously commented, "It's unreasonable to make such a big deal over the death of a fisherman."


title: Nuclear testing at Bikini Atoll

text: The 17-shot Redwing series followed—11 tests at Enewetak Atoll and six at Bikini. The island residents had been promised that they would be able to return home to Bikini, but the government thwarted that indefinitely by deciding to resume nuclear testing at Bikini in 1954. During 1954, 1956, and 1958, 21 more nuclear bombs were detonated at Bikini, yielding a total of 75 Mt of TNT (310 PJ), equivalent to more than three thousand "Baker" bombs. The 3.8 Mt of TNT Redwing "Cherokee" test was the only air burst. Air bursts distribute fallout in a large area, but surface bursts produce intense local fallout. These tests were followed by the 33-shot Hardtack tests, which began in late April 1958. The last of ten tests were detonated on Bikini Atoll on July 22, 1958.


title: Nuclear testing at Bikini Atoll

text: The following above-ground nuclear device tests were conducted on or near Bikini Atoll from 1946 to 1958, comprising 15.1% of total test yield worldwide. These dates are given in US Eastern time zone The days of the week are a day earlier than they were at Bikini.


title: Nuclear testing at Bikini Atoll

text: In 1947, the United States petitioned the United Nations Security Council to designate the islands of Micronesia a United Nations Strategic Trust Territory. This was the only strategic trust ever granted by the Security Council. The U.S. Navy controlled the trust from a headquarters in Guam until 1951, when the Department of the Interior took over control, administering the territory from a base in Saipan. The directive stipulated that the U.S. would "promote the economic advancement and self-sufficiency of the inhabitants" and "protect the inhabitants against the loss of their lands and resources".


title: Nuclear testing at Bikini Atoll

text: The residents of Bikini Atoll were left alone on Rongerik Atoll from July 1946 through July 1947. Leonard E. Mason was an anthropologist from the University of Hawaii; he visited the islanders on Rongerik Atoll in January 1948 and found that they were starving. A team of U.S. investigators concluded in late 1947 that the islanders must be moved immediately. Press from around the world harshly criticized the U.S. Navy for ignoring them. Columnist Harold Ickes wrote that "the natives are actually and literally starving to death."


title: Nuclear testing at Bikini Atoll

text: The Navy then selected Ujelang Atoll for their temporary home, and some young men from the Bikini Atoll population went ahead to begin constructing living accommodations. But U.S. Trust Authorities decided to use Enewetak Atoll as a second nuclear weapons test site, and they relocated Enewetak's residents to Ujelang Atoll to the homes built for the Bikini Islanders.


title: Nuclear testing at Bikini Atoll

text: In March 1948, 184 malnourished Bikini islanders were temporarily relocated again to Kwajalein Atoll. In June 1948, the Bikini residents chose Kili Island as a long-term home. The () island is one of the smallest in the Marshall Island chain; it was uninhabited and was not ruled by a paramount "iroij" (king). The Bikini islanders moved there in November 1948.


title: Nuclear testing at Bikini Atoll

text: President Lyndon B. Johnson promised the 540 Bikini Atoll families living on Kili and other islands in June 1968 that they would be able to return to their home, based on scientific advice that the radiation levels were sufficiently reduced. But the Atomic Energy Commission learned that the coconut crabs, an essential food source, retained high levels of radioactivity and could not be eaten. The Bikini Council voted to delay a return to the island as a result.


title: Nuclear testing at Bikini Atoll

text: In 1987, a few Bikini elders returned to the island to re-establish old property lines. Construction crews began building a hotel on Bikini and installed generators, desalinators, and power lines. A packed coral and sand runway still exists on Enyu Island. Three extended families moved back to their home island in 1972 despite the risk, eventually totaling about 100 people. But 10 years later, a team of French scientists found that some wells were too radioactive for use and determined that the pandanus and breadfruit were also dangerous for human consumption. Women were experiencing miscarriages, stillbirths, and genetic abnormalities in their children. The U.S.-administered Strategic Trust Territory decided that the islanders had to be evacuated from the atoll a second time.


title: Nuclear testing at Bikini Atoll

text: An 11-year-old boy who was born on Bikini in 1971 died from cancer that was linked to radiation exposure that he received on Bikini. The records obtained by the Marshallese Nuclear Claims Tribunal later revealed that Dr. Robert Conard, head of Brookhaven National Laboratory (BNL)'s medical team in the Marshall Islands, understated the risk of returning to the atoll. BNL then contracted Dr. Konrad Kotrady to treat the Marshall Island residents. In 1977, he wrote a 14-page report to BNL that questioned the accuracy of Brookhaven's prior work on the islands. The Bikini Atoll islanders grew to distrust the official reports of the U.S. scientists.


title: Nuclear testing at Bikini Atoll

text: The special International Atomic Energy Agency (IAEA) Bikini Advisory Group determined in 1997 that it was "safe to walk on all of the islands" and that the residual radioactivity was "not hazardous to health at the levels measured". They further stated that "the main radiation risk would be from the food", but they also added that "eating coconuts or breadfruit from Bikini Island occasionally would be no cause for concern". IAEA estimated that living in the atoll and consuming local food would result in an effective dose of about 15 mSv/a.


title: Nuclear testing at Bikini Atoll

text: The leaders of the Bikini community have insisted since the early 1980s that the top of soil should be excavated from the entire island. Scientists reply that removing the soil would rid the island of cesium-137, but it would also severely damage the environment, turning the atoll into a virtual wasteland of windswept sand. The Bikini Council has repeatedly contended that removing the topsoil is the only way to guarantee safe living conditions for future generations.


title: Nuclear testing at Bikini Atoll

text: In 1997, researchers found that the dose received from background radiation on the island was between 2.4 mSv/a—the same as natural background radiation—and 4.5 mSv/a, assuming that residents consumed a diet of imported foods. The local food supply is still irradiated and the group did not recommend resettling the island. A 1998 IAEA report found that Bikini should not be permanently resettled because of dangerous levels of radiation in the locally produced food. A permanent rehabitation would likely require the use of potassium fertilizer.


title: Nuclear testing at Bikini Atoll

text: A 2002 survey found that the coral inside the Bravo Crater has partially recovered. Zoe Richards of the ARC Centre of Excellence for Coral Reef Studies and James Cook University observed matrices of branching Porites coral up to 8 m high.


title: Nuclear testing at Bikini Atoll

text: The Bikini islanders sued the United States for the first time in 1975, and they demanded a radiological study of the northern islands. The United States set up "The Hawaiian Trust Fund for the People of Bikini" in 1975, totaling $3 million. Residents were removed from the island in 1978, and the government added $3 million to the fund and created "The Resettlement Trust Fund for the People of Bikini", containing $20 million in 1982. The government added another $90 million to that fund to pay to clean up, reconstruct homes and facilities, and resettle the islanders on Bikini and Eneu islands.


title: Nuclear testing at Bikini Atoll

text: In 1983, the U.S. and the Marshall islanders signed the Compact of Free Association which gave the Marshall Islands independence. The Compact became effective in 1986 and was subsequently modified by the Amended Compact that became effective in 2004. It also established the Nuclear Claims Tribunal, which was given the task of adjudicating compensation for victims and families affected by the nuclear testing program. Section 177 of the compact provided for reparations to the Bikini islanders and other northern atolls for damages. It included $75 million to be paid over 15 years. On March 5, 2001, the Nuclear Claims Tribunal ruled against the United States for damages done to the islands and its people.


title: Nuclear testing at Bikini Atoll

text: The payments began in 1987 with $2.4 million paid annually to the entire Bikini population, while the remaining $2.6 million is paid into "The Bikini Claims Trust Fund". This trust is intended to exist in perpetuity and to provide the islanders a 5% payment from the trust annually. The United States provided $150 million in compensation for damage caused by the nuclear testing program and their displacement from their home island.


title: Nuclear testing at Bikini Atoll

text: By 2001, 70 of the 167 relocated residents were still alive, and the entire population had grown to 2,800. Most of the islanders and their descendants live on Kili, in Majuro, or in the United States. Only a few living people were born on the Bikini Atoll. Most of the younger descendants have never lived there or even visited. The population is growing at a four percent growth rate, so increasing numbers are taking advantage of terms in the Marshall Islands' Compact of Free Association that allow them to obtain jobs in the United States.


title: Nuclear testing at Bikini Atoll

text: Stanford University professor Steve Palumbi led a study in 2017 that reported on ocean life that seems highly resilient to the effects of radiation poisoning. The team described substantial diversity in the marine ecosystem, with animals appearing healthy to the naked eye. According to Palumbi, the atoll's "lagoon is full of schools of fish all swirling around the living coral. In a strange way they are protected by the history of this place, the fish populations are better than in some other places because they have been left alone, the sharks are more abundant and the coral are big. It is a remarkable environment, quite odd." Both corals and long-lived animals such as coconut crabs should be vulnerable to radiation-induced cancers, and understanding how they have thrived might lead to discoveries about preserving DNA. Pambuli notes that the Bikini Atoll is "an ironic setting for research that might help people live longer". PBS documented field work undertaken by Palumbi and his graduate student Elora López on Bikini Atoll for the second episode ("Violent") of their series "Big Pacific." The episode explored "species, natural phenomena and behaviors of the Pacific Ocean" and the way that the team is using DNA sequencing to study the rate and pattern of any mutations. López suggested possible explanations for the health of the marine life to "The Stanford Daily", such as a mechanism for DNA repair that is superior to that possessed by humans, or a method of maintaining a genome in the face of nuclear radiation.


title: Nuclear testing at Bikini Atoll

text: The area has effectively become an unplanned marine-life sanctuary; this has also occurred in Europe in the Chernobyl exclusion zone, where scientists are studying the effects of radiation on animal life. Most fish have relatively short lifespans, and Palumbi suggested that "it is possible the worst-affected fish died off many decades ago… and the fish living in Bikini Atoll today are only subject to low levels of radiation exposure as they frequently swim in and out of the atoll." Nurse sharks have two dorsal fins, but Palumbi's team observed individuals with only a single fin, and they theorized that they might be mutations. Pambuli and his team have focussed on the hubcap-sized crabs, as their coconut diet is contaminated with radioactive caesium-137 from ground water, and on the corals, because both have longer life spans that allow the scientists "to delve into what effect the radiation exposure has had on the animals' DNA after building up in their systems for many years."


title: Nuclear testing at Bikini Atoll

text: Bikini Atoll remains uninhabitable for humans due to what United Nations reporter Călin Georgescu described as "near-irreversible environmental contamination". Gamma radiation levels in 2016 averaged 184 mrem yr (1.84 mSv/a), well above the maximum allowed for human habitation, thereby rendering the water, seafood, and plants unsafe for human consumption. Timothy Jorgensen reports on the increased cancer risk among the residents of the nearby islands, especially for leukemia and thyroid cancers.


title: Nuclear testing at Bikini Atoll

text: The Castle Bravo test produced the highest fallout levels in history. The detonation produced an explosion approximately 2.5 times the predicted 6.0 megatons, equal to 15 Mt of TNT. The residents of Rongelap and Utirik atolls were exposed to high levels of radiation, the heaviest of which was in the form of pulverized surface coral from the detonation. They experienced mild radiation sickness including nausea, vomiting, and diarrhea. Several weeks later many people began suffering from alopecia (hair loss) and skin lesions. The fallout was the source of most people's radiation exposure, which has been linked to increases in leukemia and thyroid cancer. Residents of the Marshall Islands who received significant exposure to radionuclides incurred a much greater risk of developing cancer. There is a presumed association between radiation levels and female reproductive system functioning.


title: Nuclear testing at Bikini Atoll

text: The female population of the Marshall Islands have a sixty times greater cervical cancer mortality than a comparable mainland United States population. The Islands populations also have a five times greater likelihood of breast or gastrointestinal mortality, and lung cancer mortality is three times higher than the mainland population. The male population on the Marshall Islands' lung cancer mortality is four times greater than the overall United States rates, and the oral cancer rates are ten times greater. Fallout produced from nuclear tests affected the residents externally and internally. External irradiation was caused by gamma rays that originated from fallout on the ground. While the levels of external radiation exposure can be reduced by sheltering indoors, the islanders spent most of their time outside. Internal exposure to radiation can occur through inhalation, ingestion, and skin exposure. The greatest exposure is from consuming contaminated food like coconut, pandanus, papaya, banana, arrowroot, taro, limes, breadfruit, and the ducks, pigs, and chickens raised on the islands.


title: Nuclear testing at Bikini Atoll

text: Food shipped into the islands could also be irradiated by contaminated cooking utensils. Iodine-131, a highly radioactive isotope, can be ingested or inhaled and is concentrated in a person's thyroid.


title: Feminizing hormone therapy

text: Feminizing hormone therapy, also known as transfeminine hormone therapy, is hormone therapy and sex reassignment therapy to change the secondary sex characteristics of transgender people from masculine or androgynous to feminine. It is a common type of transgender hormone therapy (another being masculinizing hormone therapy) and is used to treat transgender women and non-binary transfeminine individuals. Some, in particular intersex people but also some non-transgender people, take this form of therapy according to their personal needs and preferences.


title: Feminizing hormone therapy

text: The purpose of the therapy is to cause the development of the secondary sex characteristics of the desired sex, such as breasts and a feminine pattern of hair, fat, and muscle distribution. It cannot undo many of the changes produced by naturally occurring puberty, which may necessitate surgery and other treatments to reverse (see below). The medications used for feminizing hormone therapy include estrogens, antiandrogens, progestogens, and gonadotropin-releasing hormone modulators (GnRH modulators).


title: Feminizing hormone therapy

text: Feminizing hormone therapy has been shown to likely reduce the distress and discomfort associated with gender dysphoria.


title: Feminizing hormone therapy

text: Many physicians operate by the World Professional Association of Transgender Health (WPATH) Standards of Care (SoC) model and require psychotherapy and a letter of recommendation from a psychotherapist in order for a transgender person to obtain hormone therapy. Other physicians operate by an informed consent model and have no requirements for transgender hormone therapy aside from consent. Medications used in transgender hormone therapy are also sold without a prescription on the Internet by unregulated online pharmacies, and some transgender women purchase these medications and treat themselves using a do-it-yourself (DIY) or self-medication approach. Many transgender individuals discuss and share information on DIY hormone therapy on Reddit communities such as /r/TransDIY and /r/MtFHRT. One reason that many transgender people turn to DIY hormone therapy is due to long waiting lists of up to years for standard physician-based hormone therapy in some parts of the world such as the United Kingdom, as well as due to the often high costs of seeing a physician and the restrictive criteria that make some ineligible for treatment.


title: Feminizing hormone therapy

text: The accessibility of transgender hormone therapy differs throughout the world and throughout individual countries.


title: Feminizing hormone therapy

text: A variety of different sex-hormonal medications are used in feminizing hormone therapy for transgender women. These include estrogens to induce feminization and suppress testosterone levels; antiandrogens such as androgen receptor antagonists, antigonadotropins, GnRH modulators, and 5α-reductase inhibitors to further oppose the effects of androgens like testosterone; and progestogens for various possible though uncertain benefits. An estrogen in combination with an antiandrogen is the mainstay of feminizing hormone therapy for transgender women.


title: Feminizing hormone therapy

text: Estrogens are the major sex hormones in women, and are responsible for the development and maintenance of feminine secondary sexual characteristics, such as breasts, wide hips, and a feminine pattern of fat distribution. Estrogens act by binding to and activating the estrogen receptor (ER), their biological target in the body. A variety of different forms of estrogens are available and used medically. The most common estrogens used in transgender women include estradiol, which is the predominant natural estrogen in women, and estradiol esters such as estradiol valerate and estradiol cypionate, which are prodrugs of estradiol. Conjugated estrogens (Premarin), which are used in menopausal hormone therapy, and ethinylestradiol, which is used in birth control pills, have been used in transgender women in the past, but are no longer recommended and are rarely used today due to their higher risks of blood clots and cardiovascular problems. Estrogens may be administered orally, sublingually, transdermally/topically (via patch or gel), rectally, by intramuscular or subcutaneous injection, or by an implant. Parenteral (non-oral) routes are preferred, owing to a minimal or negligible risk of blood clots and cardiovascular issues.


title: Feminizing hormone therapy

text: In addition to producing feminization, estrogens have antigonadotropic effects and suppress gonadal sex hormone production. They are mainly responsible for the suppression of testosterone levels in transgender women. Levels of estradiol of 200 pg/mL and above suppress testosterone levels by about 90%, while estradiol levels of 500 pg/mL and above suppress testosterone levels by about 95%, or to an equivalent extent as surgical castration and GnRH modulators. Lower levels of estradiol can also considerably but incompletely suppress testosterone production. When testosterone levels are insufficiently suppressed by estradiol alone, antiandrogens can be used to suppress or block the effects of residual testosterone. Oral estradiol often has difficulty adequately suppressing testosterone levels, due to the relatively low estradiol levels achieved with it.


title: Feminizing hormone therapy

text: Prior to orchiectomy (surgical removal of the gonads) or sex reassignment surgery, the doses of estrogens used in transgender women are often higher than replacement doses used in cisgender women. This is to help suppress testosterone levels. The Endocrine Society (2017) recommends maintaining estradiol levels roughly within the normal average range for premenopausal women of about 100 to 200 pg/mL. However, it notes that these physiological levels of estradiol are usually unable to suppress testosterone levels into the female range. A 2018 Cochrane review proposal questioned the notion of keeping estradiol levels lower in transgender women, which results in incomplete suppression of testosterone levels and necessitates the addition of antiandrogens. The review proposal noted that high-dose parenteral estradiol is known to be safe. The Endocrine Society itself recommends dosages of injected estradiol esters that result in estradiol levels markedly in excess of the normal female range, for instance 10 mg per week estradiol valerate by intramuscular injection. A single such injection results in estradiol levels of about 1,250 pg/mL at peak and levels of around 200 pg/mL after 7 days. Dosages of estrogens can be reduced after an orchiectomy or sex reassignment surgery, when gonadal testosterone suppression is no longer needed.


title: Feminizing hormone therapy

text: Antiandrogens are medications that prevent the effects of androgens in the body. Androgens, such as testosterone and dihydrotestosterone (DHT), are the major sex hormones in individuals with testes, and are responsible for the development and maintenance of masculine secondary sex characteristics, such as a deep voice, broad shoulders, and a masculine pattern of hair, muscle, and fat distribution. In addition, androgens stimulate sex drive and the frequency of spontaneous erections and are responsible for acne, body odor, and androgen-dependent scalp hair loss. Androgens also have functional antiestrogenic effects in the breasts and oppose estrogen-mediated breast development, even at low levels. Androgens act by binding to and activating the androgen receptor, their biological target in the body. Antiandrogens work by blocking androgens from binding to the androgen receptor and/or by inhibiting or suppressing the production of androgens.


title: Feminizing hormone therapy

text: Antiandrogens that directly block the androgen receptor are known as androgen receptor antagonists or blockers, while antiandrogens that inhibit the enzymatic biosynthesis of androgens are known as androgen synthesis inhibitors and antiandrogens that suppress androgen production in the gonads are known as antigonadotropins. Estrogens and progestogens are antigonadotropins and hence are functional antiandrogens. The purpose of the use of antiandrogens in transgender women is to block or suppress residual testosterone that is not suppressed by estrogens alone. Additional antiandrogen therapy is not necessarily required if testosterone levels are in the normal female range or if the person has undergone orchiectomy. However, individuals with testosterone levels in the normal female range and with persisting androgen-dependent skin and/or hair symptoms, such as acne, seborrhea, oily skin, or scalp hair loss, can potentially still benefit from the addition of an antiandrogen, as antiandrogens can reduce or eliminate such symptoms.


title: Feminizing hormone therapy

text: Steroidal antiandrogens are antiandrogens that resemble steroid hormones like testosterone and progesterone in chemical structure. They are the most commonly used antiandrogens in transgender women. Spironolactone (Aldactone), which is relatively safe and inexpensive, is the most frequently used antiandrogen in the United States. Cyproterone acetate (Androcur), which is unavailable in the United States, is widely used in Europe, Canada, and the rest of the world. Medroxyprogesterone acetate (Provera, Depo-Provera), a similar medication, is sometimes used in place of cyproterone acetate in the United States.


title: Feminizing hormone therapy

text: Spironolactone is an antimineralocorticoid (antagonist of the mineralocorticoid receptor) and potassium-sparing diuretic, which is mainly used to treat high blood pressure, edema, high aldosterone levels, and low potassium levels caused by other diuretics, among other uses. Spironolactone is an antiandrogen as a secondary and originally unintended action. It works as an antiandrogen mainly by acting as an androgen receptor antagonist. The medication is also a weak steroidogenesis inhibitor, and inhibits the enzymatic synthesis of androgens. However, this action is of low potency, and spironolactone has mixed and inconsistent effects on hormone levels. In any case, testosterone levels are usually unchanged by spironolactone. Studies in transgender women have found testosterone levels to be unaltered with spironolactone or to be decreased. Spironolactone is described as a relatively weak antiandrogen. It is widely used in the treatment of acne, excessive hair growth, and hyperandrogenism in women, who have much lower testosterone levels than men. Because of its antimineralocorticoid activity, spironolactone has antimineralocorticoid side effects and can cause high potassium levels. Hospitalization and/or death can potentially result from high potassium levels due to spironolactone, but the risk of high potassium levels in people taking spironolactone appears to be minimal in those without risk factors for it. As such, monitoring of potassium levels may not be necessary in most cases. Spironolactone has been found to decrease the bioavailability of high doses of oral estradiol. Although widely employed, the use of spironolactone as an antiandrogen in transgender women has recently been questioned due to the various shortcomings of the medication for such purposes.


title: Feminizing hormone therapy

text: Cyproterone acetate is an antiandrogen and progestin which is used in the treatment of numerous androgen-dependent conditions and is also used as a progestogen in birth control pills. It works primarily as an antigonadotropin, secondarily to its potent progestogenic activity, and strongly suppresses gonadal androgen production. Cyproterone acetate at a dosage of 5 to 10 mg/day has been found to lower testosterone levels in men by about 50 to 70%, while a dosage of 100 mg/day has been found to lower testosterone levels in men by about 75%. The combination of 25 mg/day cyproterone acetate and a moderate dosage of estradiol has been found to suppress testosterone levels in transgender women by about 95%. In combination with estrogen, 10, 25, and 50 mg/day cyproterone acetate have all shown the same degree of testosterone suppression. In addition to its actions as an antigonadotropin, cyproterone acetate is an androgen receptor antagonist. However, this action is relatively insignificant at low dosages, and is more important at the high doses of cyproterone acetate that are used in the treatment of prostate cancer (100–300 mg/day). Cyproterone acetate can cause elevated liver enzymes and liver damage, including liver failure. However, this occurs mostly in prostate cancer patients who take very high doses of cyproterone acetate; liver toxicity has not been reported in transgender women. Cyproterone acetate also has a variety of other adverse effects, such as fatigue and weight gain, and risks, such as blood clots and benign brain tumors, among others. Periodic monitoring of liver enzymes and prolactin levels may be advisable during cyproterone acetate therapy.


title: Feminizing hormone therapy

text: Medroxyprogesterone acetate is a progestin that is related to cyproterone acetate and is sometimes used as an alternative to it. It is specifically used as an alternative to cyproterone acetate in the United States, where cyproterone acetate is not approved for medical use and is unavailable. Medroxyprogesterone acetate suppresses testosterone levels in transgender women similarly to cyproterone acetate. Oral medroxyprogesterone acetate has been found to suppress testosterone levels in men by about 30 to 75% across a dosage range of 20 to 100 mg/day. In contrast to cyproterone acetate however, medroxyprogesterone acetate is not also an androgen receptor antagonist. Medroxyprogesterone acetate has similar side effects and risks as cyproterone acetate, but is not associated with liver problems.


title: Feminizing hormone therapy

text: Numerous other progestogens and by extension antigonadotropins have been used to suppress testosterone levels in men and are likely useful for such purposes in transgender women as well. Progestogens alone are in general able to suppress testosterone levels in men by a maximum of about 70 to 80%, or to just above female/castrate levels when used at sufficiently high doses. The combination of a sufficient dosage of a progestogen with very small doses of an estrogen (e.g., as little as 0.5–1.5 mg/day oral estradiol) is synergistic in terms of antigonadotropic effect and is able to fully suppress gonadal testosterone production, reducing testosterone levels to the female/castrate range.


title: Feminizing hormone therapy

text: Nonsteroidal antiandrogens are antiandrogens which are nonsteroidal and hence unrelated to steroid hormones in terms of chemical structure. These medications are primarily used in the treatment of prostate cancer, but are also used for other purposes such as the treatment of acne, excessive facial/body hair growth, and high androgen levels in women. Unlike steroidal antiandrogens, nonsteroidal antiandrogens are highly selective for the androgen receptor and act as pure androgen receptor antagonists. Similarly to spironolactone however, they do not lower androgen levels, and instead work exclusively by preventing androgens from activating the androgen receptor. Nonsteroidal antiandrogens are more efficacious androgen receptor antagonists than are steroidal antiandrogens, and for this reason, in conjunction with GnRH modulators, have largely replaced steroidal antiandrogens in the treatment of prostate cancer.


title: Feminizing hormone therapy

text: The nonsteroidal antiandrogens that have been used in transgender women include the first-generation medications flutamide (Eulexin), nilutamide (Anandron, Nilandron), and bicalutamide (Casodex). Newer and even more efficacious second-generation nonsteroidal antiandrogens like enzalutamide (Xtandi), apalutamide (Erleada), and darolutamide (Nubeqa) also exist, but are very expensive due to generics being unavailable and have not been used in transgender women. Flutamide and nilutamide have relatively high toxicity, including considerable risks of liver damage and lung disease. Due to its risks, the use of flutamide in cisgender and transgender women is now limited and discouraged. Flutamide and nilutamide have largely been superseded by bicalutamide in clinical practice, with bicalutamide accounting for almost 90% of nonsteroidal antiandrogen prescriptions in the United States by the mid-2000s. Bicalutamide is said to have excellent tolerability and safety relative to flutamide and nilutamide, as well as in comparison to cyproterone acetate. It has few to no side effects in women. Despite its greatly improved tolerability and safety profile however, bicalutamide does still have a small risk of elevated liver enzymes and association with very rare cases of liver damage and lung disease.


title: Feminizing hormone therapy

text: Nonsteroidal antiandrogens like bicalutamide may be a particularly favorable option for transgender women who wish to preserve sex drive, sexual function, and/or fertility, relative to antiandrogens that suppress testosterone levels and can greatly disrupt these functions such as cyproterone acetate and GnRH modulators. However, estrogens suppress testosterone levels and at high doses can markedly disrupt sex drive and function and fertility on their own. Moreover, disruption of gonadal function and fertility by estrogens may be permanent after extended exposure.


title: Feminizing hormone therapy

text: GnRH modulators are antigonadotropins and hence functional antiandrogens. In both males and females, gonadotropin-releasing hormone (GnRH) is produced in the hypothalamus and induces the secretion of the gonadotropins luteinizing hormone (LH) and follicle-stimulating hormone (FSH) from the pituitary gland. The gonadotropins signal the gonads to make sex hormones such as testosterone and estradiol. GnRH modulators bind to and inhibit the GnRH receptor, thereby preventing gonadotropin release. As a result of this, GnRH modulators are able to completely shut-down gonadal sex hormone production, and can decrease testosterone levels in men and transgender women by about 95%, or to an equivalent extent as surgical castration. GnRH modulators are also commonly known as GnRH analogues. However, not all clinically used GnRH modulators are analogues of GnRH.


title: Feminizing hormone therapy

text: There are two types of GnRH modulators: GnRH agonists and GnRH antagonists. These medications have the opposite action on the GnRH receptor but paradoxically have the same therapeutic effects. GnRH agonists, such as leuprorelin (Lupron), goserelin (Zoladex), and buserelin (Suprefact), are GnRH receptor superagonists, and work by producing profound desensitization of the GnRH receptor such that the receptor becomes non-functional. This occurs because GnRH is normally released in pulses, but GnRH agonists are continuously present, and this results in excessive downregulation of the receptor and ultimately a complete loss of function. At the initiation of treatment, GnRH agonists are associated with a "flare" effect on hormone levels due to acute overstimulation of the GnRH receptor. In men, LH levels increase by up to 800%, while testosterone levels increase to about 140 to 200% of baseline. Gradually however, the GnRH receptor desensitizes; testosterone levels peak after about 2 to 4 days, return to baseline after about 7 to 8 days, and are reduced to castrate levels within 2 to 4 weeks. Antigonadotropins such as estrogens and cyproterone acetate as well as nonsteroidal antiandrogens such as flutamide and bicalutamide can be used beforehand and concomitantly to reduce or prevent the effects of the testosterone flare caused by GnRH agonists. In contrast to GnRH agonists, GnRH antagonists, such as degarelix (Firmagon) and elagolix (Orilissa), work by binding to the GnRH receptor without activating it, thereby displacing GnRH from the receptor and preventing its activation. Unlike with GnRH agonists, there is no initial surge effect with GnRH antagonists; the therapeutic effects are immediate, with sex hormone levels being reduced to castrate levels within a few days.


title: Feminizing hormone therapy

text: GnRH modulators are highly effective for testosterone suppression in transgender women and have few or no side effects when sex hormone deficiency is avoided with concomitant estrogen therapy. However, GnRH modulators tend to be very expensive (typically to per year in the United States), and are often denied by medical insurance. GnRH modulator therapy is much less economical than surgical castration, and is less convenient than surgical castration in the long-term as well. Because of their costs, many transgender women cannot afford GnRH modulators and must use other, often less effective options for testosterone suppression. GnRH agonists are prescribed as standard practice for transgender women in the United Kingdom however, where the National Health Service (NHS) covers them. This is in contrast to the rest of Europe and to the United States. Another drawback of GnRH modulators is that most of them are peptides and are not orally active, requiring administration by injection, implant, or nasal spray. However, non-peptide and orally active GnRH antagonists, elagolix (Orilissa) and relugolix (Relumina), were introduced for medical use in 2018 and 2019, respectively. But they are under patent protection and, as with other GnRH modulators, are very expensive at present.


title: Feminizing hormone therapy

text: In adolescents of either sex with relevant indicators, GnRH modulators can be used to stop undesired pubertal changes for a period without inducing any changes toward the sex with which the patient currently identifies. There is considerable controversy over the earliest age at which it is clinically, morally, and legally safe to use GnRH modulators, and for how long. The sixth edition of the World Professional Association for Transgender Health's Standards of Care permit it from Tanner stage 2 but do not allow the addition of hormones until age 16, which could be five or more years later.


title: Feminizing hormone therapy

text: 5α-Reductase inhibitors are inhibitors of the enzyme 5α-reductase, and are a type of specific androgen synthesis inhibitor. 5α-Reductase is an enzyme that is responsible for the conversion of testosterone into the more potent androgen dihydrotestosterone (DHT). There are three different isoforms of 5α-reductase, types 1, 2, and 3, and these three isoforms show different patterns of expression in the body. Relative to testosterone, DHT is about 2.5- to 10-fold more potent as an agonist of the androgen receptor. As such, 5α-reductase serves to considerably potentiate the effects of testosterone. However, 5α-reductase is expressed only in specific tissues, such as skin, hair follicles, and the prostate gland, and for this reason, conversion of testosterone into DHT happens only in certain parts of the body. Furthermore, circulating levels of total and free DHT in men are very low at about 1/10th and 1/20th those of testosterone, respectively, and DHT is efficiently inactivated into weak androgens in various tissues such as muscle, fat, and liver. As such, it is thought that DHT plays little role as a systemic androgen hormone and serves more as a means of locally potentiating the androgenic effects of testosterone in a tissue-specific manner. Conversion of testosterone into DHT by 5α-reductase plays an important role in male reproductive system development and maintenance (specifically of the penis, scrotum, prostate gland, and seminal vesicles), male-pattern facial/body hair growth, and scalp hair loss, but has little role in other aspects of masculinization. Besides the involvement of 5α-reductase in androgen signaling, it is also required for the conversion of steroid hormones such as progesterone and testosterone into neurosteroids like allopregnanolone and 3α-androstanediol, respectively.


title: Feminizing hormone therapy

text: 5α-Reductase inhibitors include finasteride and dutasteride. Finasteride is a selective inhibitor of 5α-reductase types 2 and 3, while dutasteride is an inhibitor of all three isoforms of 5α-reductase. Finasteride can decrease circulating DHT levels by up to 70%, whereas dutasteride can decrease circulating DHT levels by up to 99%. Conversely, 5α-reductase inhibitors do not decrease testosterone levels, and may actually increase them slightly. 5α-Reductase inhibitors are used primarily in the treatment of benign prostatic hyperplasia, a condition in which the prostate gland becomes excessively large due to stimulation by DHT and causes unpleasant urogenital symptoms. They are also used in the treatment of androgen-dependent scalp hair loss in men and women. The medications are able to prevent further scalp hair loss in men and can restore some scalp hair density. Conversely, the effectiveness of 5α-reductase inhibitors in the treatment of scalp hair loss in women is less clear. This may be because androgen levels are much lower in women, in whom they may not play as important of a role in scalp hair loss. 5α-Reductase inhibitors are also used to treat hirsutism (excessive body/facial hair growth) in women, and are very effective for this indication. Dutasteride has been found to be significantly more effective than finasteride in the treatment of scalp hair loss in men, which has been attributed to its more complete inhibition of 5α-reductase and by extension decrease in DHT production. In addition to their antiandrogenic uses, 5α-reductase inhibitors have been found to reduce adverse affective symptoms in premenstrual dysphoric disorder in women. This is thought to be due to prevention by 5α-reductase inhibitors of the conversion of progesterone into allopregnanolone during the luteal phase of the menstrual cycle.


title: Feminizing hormone therapy

text: 5α-Reductase inhibitors are sometimes used as a component of feminizing hormone therapy for transgender women in combination with estrogens and/or other antiandrogens. They may have beneficial effects limited to improvement of scalp hair loss, body hair growth, and possibly skin symptoms such as acne. However, little clinical research on 5α-reductase inhibitors in transgender women has been conducted, and evidence of their efficacy and safety in this group is limited. Moreover, 5α-reductase inhibitors have only mild and specific antiandrogenic activity, and are not recommended as general antiandrogens.


title: Feminizing hormone therapy

text: 5α-Reductase inhibitors have minimal side effects and are well tolerated in both men and women. In men, the most common side effect is sexual dysfunction (0.9–15.8% incidence), which may include decreased libido, erectile dysfunction, and reduced ejaculate. Another side effect in men is breast changes, such as breast tenderness and gynecomastia (2.8% incidence). Due to decreased levels of androgens and/or neurosteroids, 5α-reductase inhibitors may slightly increase the risk of depression (~2.0% incidence). There are reports that a small percentage of men may experience persistent sexual dysfunction and adverse mood changes even after discontinuation of 5α-reductase inhibitors. Some of the possible side effects of 5α-reductase inhibitors in men, such as gynecomastia and sexual dysfunction, are actually welcome changes for many transgender women. In any case, caution may be warranted in using 5α-reductase inhibitors in transgender women, as this group is already at a high risk for depression and suicidality.


title: Feminizing hormone therapy

text: Progesterone, a progestogen, is the other of the two major sex hormones in women. It is mainly involved in the regulation of the female reproductive system, the menstrual cycle, pregnancy, and lactation. The non-reproductive effects of progesterone are fairly insignificant. Unlike estrogens, progesterone is not known to be involved in the development of female secondary sexual characteristics, and hence is not believed to contribute to feminization in women. One area of particular interest in terms of the effects of progesterone in women is breast development. Estrogens are responsible for the development of the ductal and connective tissues of the breasts and the deposition of fat into the breasts during puberty in girls. Conversely, high levels of progesterone, in conjunction with other hormones such as prolactin, are responsible for the lobuloalveolar maturation of the mammary glands during pregnancy. This allows for lactation and breastfeeding after childbirth. Although progesterone causes the breasts to change during pregnancy, the breasts undergo involution and revert to their pre-pregnancy composition and size after the cessation of breastfeeding. Every pregnancy, lobuloalveolar maturation occurs again anew.


title: Feminizing hormone therapy

text: There are two types of progestogens: progesterone, which is the natural and bioidentical hormone in the body; and progestins, which are synthetic progestogens. There are dozens of clinically used progestins. Certain progestins, namely cyproterone acetate and medroxyprogesterone acetate and as described previously, are used at high doses as functional antiandrogens due to their antigonadotropic effects to help suppress testosterone levels in transgender women. Aside from the specific use of testosterone suppression however, there are no other indications of progestogens in transgender women at present. In relation to this, the use of progestogens in transgender women is controversial, and they are not otherwise routinely prescribed or recommended. Besides progesterone, cyproterone acetate, and medroxyprogesterone acetate, other progestogens that have been reported to have been used in transgender women include hydroxyprogesterone caproate, dydrogesterone, norethisterone acetate, and drospirenone. Progestins in general largely have the same progestogenic effects however, and in theory, any progestin could be used in transgender women.


title: Feminizing hormone therapy

text: Clinical research on the use of progestogens in transgender women is very limited. Some patients and clinicians believe, on the basis of anecdotal and subjective claims, that progestogens may provide benefits such as improved breast and/or nipple development, mood, and libido in transgender women. There are no clinical studies to support such reports at present. No clinical study has assessed the use of progesterone in transgender women, and only a couple of studies have compared the use of progestins (specifically cyproterone acetate and medroxyprogesterone acetate) versus the use of no progestogen in transgender women. These studies, albeit limited in the quality of their findings, reported no benefit of progestogens on breast development in transgender women. This has also been the case in limited clinical experience. These reports are in accordance with the normal and even above-average breast development in women with complete androgen insensitivity syndrome, who lack progesterone and have no lobuloalveolar development of the mammary glands on histological examination. It is noteworthy that epithelial tissue, which makes up lobuloalveolar tissue, normally (outside of pregnancy and lactation) comprises only about 10 to 15% of the tissue of the breasts. Although the influence of progesterone on breast development is uncertain, progesterone is thought to cause reversible breast enlargement during the menstrual cycle due to local fluid retention in the breasts. This may give a misleading appearance of breast growth, and might contribute to anecdotal reports of improved breast size and/or shape with progesterone in transgender women.


title: Feminizing hormone therapy

text: Progestogens have some antiestrogenic effects in the breasts, for instance decreasing expression of the estrogen receptor and increasing expression of estrogen-metabolizing enzymes, and for this reason, have been used to treat breast pain and benign breast disorders. Progesterone levels during female puberty do not normally increase importantly until near the end of puberty in cisgender girls, a point by which most breast development has already been completed. In addition, concern has been expressed that premature exposure to progestogens during the process of breast development is unphysiological and might compromise final breast growth outcome, although this notion presently remains theoretical. Though the role of progestogens in pubertal breast development is uncertain, progesterone is essential for lobuloalveolar maturation of the mammary glands during pregnancy. Hence, progestogens are required for any transgender woman who wishes to lactate or breastfeed. A study found full lobuloalveolar maturation of the mammary glands on histological examination in transgender women treated with an estrogen and high-dose cyproterone acetate. However, lobuloalveolar development reversed with discontinuation of cyproterone acetate, indicating that continued progestogen exposure is necessary to maintain the tissue.


title: Feminizing hormone therapy

text: In terms of the effects of progestogens on sex drive, one study assessed the use of dydrogesterone to improve sexual desire in transgender women and found no benefit. Another study likewise found that oral progesterone did not improve sexual function in cisgender women.


title: Feminizing hormone therapy

text: Progestogens can have adverse effects. Oral progesterone has inhibitory neurosteroid effects and can produce side effects such as sedation, mood changes, and alcohol-like effects. Many progestins have off-target activity, such as androgenic, antiandrogenic, glucocorticoid, and antimineralocorticoid activity, and these activities likewise can contribute unwanted side effects. Furthermore, the addition of a progestin to estrogen therapy has been found to increase the risk of blood clots, cardiovascular disease (e.g., coronary heart disease and stroke), and breast cancer compared to estrogen therapy alone in postmenopausal women. Although it is unknown if these health risks of progestins occur in transgender women similarly, it cannot be ruled out that they do. High-dose progestogens increase the risk of benign brain tumors including prolactinomas and meningiomas as well. Because of their potential detrimental effects and lack of supported benefits, some researchers have argued that, aside from the purpose of testosterone suppression, progestogens should not generally be used or advocated in transgender women or should only be used for a limited duration (e.g., 2–3 years). Conversely, other researchers have argued that the risks of progestogens in transgender women are likely minimal, and that in light of potential albeit hypothetical benefits, should be used if desired. In general, some transgender women respond favorably to the effects of progestogens, while others respond negatively.


title: Feminizing hormone therapy

text: Progesterone is most commonly taken orally. However, oral progesterone has very low bioavailability, and produces relatively weak progestogenic effects even at high doses. In accordance, and in contrast to progestins, oral progesterone has no antigonadotropic effects in men even at high doses. Progesterone can also be taken by various parenteral (non-oral) routes, including sublingually, rectally, and by intramuscular or subcutaneous injection. These routes do not have the bioavailability and efficacy issues of oral progesterone, and accordingly, can produce considerable antigonadotropic and other progestogenic effects. Transdermal progesterone is poorly effective, owing to absorption issues. Progestins are usually taken orally. In contrast to progesterone, most progestins have high oral bioavailability, and can produce full progestogenic effects with oral administration. Some progestins, such as medroxyprogesterone acetate and hydroxyprogesterone caproate, are or can be used by intramuscular or subcutaneous injection instead. Almost all progestins, with the exception of dydrogesterone, have antigonadotropic effects.


title: Feminizing hormone therapy

text: Galactogogues such as the peripherally selective D receptor antagonist and prolactin releaser domperidone can be used to induce lactation in transgender women who wish to breastfeed. An extended period of combined estrogen and progestogen therapy is necessary to mature the lobuloalveolar tissue of the breasts before this can be successful. There are several published reports of lactation and/or breastfeeding in transgender women.


title: Feminizing hormone therapy

text: The World Professional Association for Transgender Health (WPATH) Standards of Care for the Health of Transgender and Gender Diverse People Version 8 (SOC8), released in September 2022, recommends against therapeutic strategies including supraphysiological estradiol levels (>200 pg/mL), use of progesterone (including rectal progesterone), use of bicalutamide, and monitoring of the ratio of estrone to estradiol. This is due to lack of data to support these approaches in transfeminine people as well as potential risks. The WPATH SOC8 also recommends against the use of 5α-reductase inhibitors such as finasteride in transfeminine people.


title: Feminizing hormone therapy

text: Many of the medications used in feminizing hormone therapy, such as estradiol, cyproterone acetate, and bicalutamide, are substrates of CYP3A4 and other cytochrome P450 enzymes. As a result, inducers of CYP3A4 and other cytochrome P450 enzymes, such as carbamazepine, phenobarbital, phenytoin, rifampin, rifampicin, and St. John's wort, among others, may decrease circulating levels of these medications and thereby decrease their effects. Conversely, inhibitors of CYP3A4 and other cytochrome P450 enzymes, such as cimetidine, clotrimazole, grapefruit juice, itraconazole, ketoconazole, and ritonavir, among others, may increase circulating levels of these medications and thereby increase their effects. The concomitant use of a cytochrome P450 inducer or inhibitor with feminizing hormone therapy may necessitate medication dosage adjustments.


title: Feminizing hormone therapy

text: The spectrum of effects of hormone therapy in transfeminine people depend on the specific medications and dosages used. In any case, the main effects of hormone therapy in transfeminine people are feminization and demasculinization, and are as follows:


title: Feminizing hormone therapy

text: Breast, nipple, and areolar development varies considerably depending on genetics, body composition, age of HRT initiation, and many other factors. Development can take a couple years to nearly a decade for some. However, many transgender women report there is often a "stall" in breast growth during transition, or significant breast asymmetry. Transgender women on HRT often experience less breast development than nontransgender women (especially if started after young adulthood). For this reason, many seek breast augmentation. Transgender patients opting for breast reduction are rare. Shoulder width and the size of the rib cage also play a role in the perceivable size of the breasts; both are usually larger in transgender women, causing the breasts to appear proportionally smaller. Thus, when a transgender woman opts to have breast augmentation, the implants used tend to be larger than those used by cisgender women.


title: Feminizing hormone therapy

text: In clinical trials, cisgender women have used stem cells from fat to regrow their breasts after mastectomies. This could some day eliminate the need for implants for transgender women.


title: Feminizing hormone therapy

text: Breast development in transgender women begins within two to three months of the start of hormone therapy and continues for up to two years. Breast development seems to be better in transgender women who have a higher body mass index. As a result, it may be beneficial to breast development for thin transgender women to gain some weight in the early phases of hormone therapy. Different estrogens, such as estradiol valerate, conjugated estrogens, and ethinylestradiol, appear to produce equivalent results in terms of breast sizes in transgender women. The sudden discontinuation of estrogen therapy has been associated with onset of galactorrhea (lactation).


title: Feminizing hormone therapy

text: Sebaceous gland activity (which is triggered by androgens) lessens, reducing oil production on the skin and scalp. Consequently, the skin becomes less prone to acne. It also becomes drier, and lotions or oils may be necessary.


title: Feminizing hormone therapy

text: Antiandrogens affect existing facial hair only slightly; patients may see slower growth and some reduction in density and coverage. In patients in their teens or early twenties, antiandrogens prevent new facial hair from developing if testosterone levels are within the normal female range.


title: Feminizing hormone therapy

text: Body hair (on the chest, shoulders, back, abdomen, buttocks, thighs, tops of hands, and tops of feet) turns, over time, from terminal ("normal") hairs to tiny, blonde vellus hairs. Arm, perianal, and perineal hair is reduced but may not turn to vellus hair on the latter two regions (some cisgender women also have hair in these areas). Underarm hair changes slightly in texture and length, and pubic hair becomes more typically female in pattern. Lower leg hair becomes less dense. All of these changes depend to some degree on genetics. Eyebrows do not change because they are not androgenic hair.


title: Feminizing hormone therapy

text: The lens of the eye changes in curvature. Because of decreased androgen levels, the meibomian glands (the sebaceous glands on the upper and lower eyelids that open up at the edges) produce less oil. Because oil prevents the tear film from evaporating, this change may cause dry eyes.


title: Feminizing hormone therapy

text: The distribution of adipose (fat) tissue changes slowly over months and years. HRT causes the body to accumulate new fat in a typically feminine pattern, including in the hips, thighs, buttocks, pubis, upper arms, and breasts. The body begins to burn old adipose tissue in the waist, shoulders, and back, making those areas smaller.


title: Feminizing hormone therapy

text: Established changes to the bone structure of the face are also unaffected by HRT. A significant majority of craniofacial changes occur during adolescence. Post-adolescent growth is considerably slower and minimal by comparison.


title: Feminizing hormone therapy

text: The psychological effects of feminizing hormone therapy are harder to define than physical changes. Because hormone therapy is usually the first physical step taken to transition, the act of beginning it has a significant psychological effect, which is difficult to distinguish from hormonally induced changes.


title: Feminizing hormone therapy

text: Some transgender women report a significant reduction in libido, depending on the dosage of antiandrogens.


title: Feminizing hormone therapy

text: Managing long-term hormonal regimens have not been studied and are difficult to estimate because research on the long-term use of hormonal therapy has not been noted. However, it is possible to speculate the outcomes of these therapies on transgender people based on the knowledge of the current effects of gonadal hormones on sexual functioning in cisgender men and women.


title: Feminizing hormone therapy

text: Firstly, if one is to decrease testosterone in feminizing gender transition, it is likely that sexual desire and arousal would be inhibited; alternatively, if high doses of estrogen negatively impact sexual desire, which has been found in some research with cisgender women, it is hypothesized that combining androgens with high levels of estrogen would intensify this outcome. To date there have not been any randomized clinical trials looking at the relationship between type and dose of transgender hormone therapy, so the relationship between them remains unclear. Typically, the estrogens given for feminizing gender transition are 2 to 3 times higher than the recommended dose for HRT in postmenopausal women. Pharmacokinetic studies indicate taking these increased doses may lead to a higher boost in plasma estradiol levels; however, the long-term side effects have not been studied and the safety of this route is unclear.


title: Feminizing hormone therapy

text: As with any pharmacological or hormone therapy, there are potential side effects, which in the case of transgender hormone therapy include changes in sexual functioning. These have the ability to significantly impact sexual functioning, either directly or indirectly through the various side effects, such as cerebrovascular disorders, obesity, and mood fluctuations.


title: Feminizing hormone therapy

text: Several studies have found that hormone therapy in transgender women causes the structure of the brain to change in the direction of female proportions. In addition, studies have found that hormone therapy in transgender women causes performance in cognitive tasks, including visuospatial, verbal memory, and verbal fluency, to shift in a more female direction.


title: Feminizing hormone therapy

text: The most significant cardiovascular risk for transgender women is the prothrombotic effect (increased blood clotting) of estrogens. This manifests most significantly as an increased risk for venous thromboembolism (VTE): deep vein thrombosis (DVT) and pulmonary embolism (PE), which occurs when blood clots from DVT break off and migrate to the lungs. Symptoms of DVT include pain or swelling of one leg, especially the calf. Symptoms of PE include chest pain, shortness of breath, fainting, and heart palpitations, sometimes without leg pain or swelling.


title: Feminizing hormone therapy

text: VTE occurs more frequently in the first year of treatment with estrogens. The risk of VTE is higher with oral non-bioidentical estrogens such as ethinylestradiol and conjugated estrogens than with parenteral formulations of estradiol such as injectable, transdermal, implantable, and intranasal. Increased risk of VTE with estrogens is thought to be due to their influence on liver protein synthesis, specifically on the production of coagulation factors. Non-bioidentical estrogens such as conjugated estrogens and especially ethinylestradiol have markedly disproportionate effects on liver protein synthesis relative to estradiol. In addition, oral estradiol has a 4- to 5-fold increased impact on liver protein synthesis than does transdermal estradiol and other parenteral estradiol routes.


title: Feminizing hormone therapy

text: Because the risks of warfarin – which is used to treat blood clots – in a relatively young and otherwise healthy population are low, while the risk of adverse physical and psychological outcomes for untreated transgender patients is high, prothrombotic mutations (such as factor V Leiden, antithrombin III, and protein C or S deficiency) are not absolute contraindications for hormonal therapy.


title: Feminizing hormone therapy

text: A 2018 cohort study of 2842 transfeminine individuals in the United States treated with a mean follow-up of 4.0 years observed an increased risk of VTE, stroke, and heart attack relative to a cisgender reference population. The estrogens used included oral estradiol (1 to 10 mg/day) and other estrogen formulations. Other medications such as antiandrogens like spironolactone were also used.


title: Feminizing hormone therapy

text: A 2019 systematic review and meta-analysis found an incidence rate of VTE of 2.3 per 1000 person-years with feminizing hormone therapy in transgender women. For comparison, the rate in the general population has been found to be 1.0–1.8 per 1000 person-years, and the rate in premenopausal women taking birth control pills has been found to be 3.5 per 1000 patient-years. There was significant heterogeneity in the rates of VTE across the included studied, and the meta-analysis was unable to perform subgroup analyses between estrogen type, estrogen route, estrogen dosage, concomitant antiandrogen or progestogen use, or patient characteristics (e.g., sex, age, smoking status, weight) corresponding to known risk factors for VTE. Due to the inclusion of some studies using ethinylestradiol, which is more thrombotic and is no longer used in transgender women, the researchers noted that the VTE risk found in their study may be an overestimate.


title: Feminizing hormone therapy

text: In a 2016 study that specifically assessed oral estradiol, the incidence of VTE in 676 transgender women who were treated for an average of 1.9 years each was only one individual, or 0.15% of the group, with an incidence of 7.8 events per 10,000 person-years. The dosage of oral estradiol used was 2 to 8 mg/day. Almost all of the transgender women were also taking spironolactone (94%), a subset were also taking finasteride (17%), and fewer than 5% were also taking a progestogen (usually oral progesterone). The findings of this study suggest that the incidence of VTE is low in transgender women taking oral estradiol.


title: Feminizing hormone therapy

text: Studies are mixed on whether the risk of breast cancer is increased with hormone therapy in transgender women. Two cohort studies found no increase in risk relative to cisgender men, whereas another cohort study found an almost 50-fold increase in risk such that the incidence of breast cancer was between that of cisgender men and cisgender women. There is no evidence that breast cancer risk in transgender women is greater than in cisgender women. Twenty cases of breast cancer in transgender women have been reported as of 2019.