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現有關於女性傾向跨性別者採用孕激素治療後的乳房發育情況的研究彙總

截至撰稿時,僅有少數幾項研究就孕激素——具備生物同質性孕酮,或形如醋酸甲羥孕酮(MPA)、醋酸環丙孕酮(CPA)的人工孕激素製劑——用於女性傾向跨性別者時對乳房發育的影響進行探討。有的論文就孕激素用於女性傾向跨性別者時的乳房發育情況作了一定回顧,其中包括 Wierckx, Gooren, & T’Sjoen (2014) 以及 Reisman, Goldstein, & Safer (2019)

Meyer et al. (1986) 就雌激素治療中加用的孕激素對女性傾向跨性別者的乳房發育和其它臨牀特徵之影響進行研究。其中,60 名女性傾向跨性別者有 15 人(25%)給予口服孕激素,多為 10 mg/天的 MPA,且要持續“至少一段較短的時間”——僅 8 人(13.3%)在整個治療期內持續服用。在該研究早期的報告中提到,觀察期內有 90% 的時間以 10 mg/天的劑量給藥,其餘時間則為 20 mg/天(Meyer et al., 1981)。在 10 mg/天劑量下,MPA 的孕激素效力大致與黃體期孕酮暴露所致效力相當(維基百科)。研究中以乳房半圍來評價乳房發育狀況(示意圖)
結果表明,孕激素治療未改變由雌激素促導的變化過程,包括實驗室檢驗結果、激素水平,以及體重、乳房增長等體徵。其中,激素水平未發生改變的結果與預期不符:在其它高質量研究中,MPA 對睾酮明顯有抑制作用(例如 Jain, Kwan, & Forcier, 2019; 維基百科)
Meyer 及其同行總結認為,在雌激素之外加用孕激素不會促進女性傾向跨性別者的乳房發育。但是,他們提到該研究中服用孕激素的個體數偏少,尚需進一步研究。

Prior et al. (1986) 和 Prior, Vigna, & Watson (1989) 將雌激素、高劑量螺內酯(100~600 mg/天)和 MPA(10~20 mg/天,序貫或連續服用)用於從未進行激素治療、或曾接受高劑量雌激素(和/或孕激素)但未合併螺內酯治療的女性傾向跨性別者,並進行研究。
研究者報告稱,依指定激素方案治療 12 個月後,乳房體積和乳頭髮育均有所增長。至研究結束前,大多數個體的乳房組織達到 A 罩杯,即直徑約達 8~14 cm。影像記錄也作為乳房發育情況之評價的一部分進行。而據研究者的自述,儘管乳房發育有所改善,但難以確認是否可歸因於螺內酯或 MPA。此外,研究開始前對睾酮的抑制效果是不充分的,而後隨研究指定的激素配方有所改善;無論 MPA 是否對乳房有直接的孕激素作用,該配方都可能促進了乳房發育。最後,不能排除研究前由雌激素誘導的乳房發育尚未停止,而後僅靠雌激素本身便足以繼續促進乳房發育的可能性。
上述研究的第一作者 Jerilynn Prior 在其它著述中聲稱,孕酮有促進乳房發育的作用,並引用上述研究以支持其論點(Prior, 2011; Prior, 2019a; Prior, 2019b; Prior, 2020)。然而,如本文和他處所述,上述研究所存在的侷限性使得其論點缺乏足夠根據(Aly, 2019)

Dittrich et al. (2005) 報告稱,經口服戊酸雌二醇合併促性腺激素釋放激素(GnRH)激動劑治療二年後,女性傾向跨性別者有 5% 報告乳房達到 C 罩杯或更大,30% 報告有 B 罩杯,35% 報告有 A 罩杯,其餘 30% 未達到 A 罩杯。但他們指出,有 70% 的個體對乳房發育情況不滿意,有意接受隆胸手術。
研究者聲稱,某些個體報告在研究開始前曾採用炔雌醇和 CPA 治療,而研究所用配方所促成的乳房體積增長等女性化效果與其相似。論文未透露其它細節。考慮到 CPA 在早期用於女性傾向跨性別者的劑量下有很強的孕激素作用,這個説法並非空穴來風。但應當注意,該研究並未應用孕激素本身或對其研究。此外,自發報告具有很大主觀性,作為評價乳房發育和乳房體積的依據是欠妥的。因此,這項研究結果對於理解孕激素和乳房發育(之關係)的價值是存疑的。

在乳房發育過程中,雌激素主要參與乳腺導管發育,而孕酮主要參與乳腺小葉的發育。Kanhai et al. (2000) 記錄了雌激素和 100 mg/天 CPA(即超高劑量孕激素)用於 14 名女性傾向跨性別者所引起的乳腺組織學變化,以及非甾體類抗雄激素製劑(氟他胺或比卡魯胺)單藥用於 2 名患前列腺癌的順性別男性所引起的乳腺改變,並加以比較。這兩種療法均可阻斷雄激素,使雌激素水平升高,且均已知有較高几率促導乳房發育或男性乳房增生。然而,這二者有一點不同:非甾體類抗雄製劑單藥並不具備孕激素效力。
乳腺活體切片顯示,在女性傾向跨性別者當中,乳腺小葉發育充分;而在男性前列腺癌患者中,僅觀察到“中等”發育、即發育不充分的乳腺小葉。該論文還指出,當女性傾向跨性別者接受性腺切除術,從而停用 CPA 之後,其乳腺小葉形成有退行傾向。研究者總結認為,有必要使乳房暴露於孕激素,以達到組織學意義上的完全發育;對女性傾向跨性別者而言亦然,其乳腺組織需暴露於孕激素以便完全模擬成熟的女性乳腺組織形態。
該研究的結果雖引人注目,但其關注點侷限於組織形態,並未真正提供任何關於乳房發育的外觀資料。有鑑於此,組織學上的差異可能不足以體現乳房體積或外形等性質的相對差異。因此,如要理解孕激素用於女性傾向跨性別者時是否可實實在在地促進乳房發育,則該研究的參考價值是有限的。

Jain, Kwan, & Forcier (2019) 對經舌下含服的雌二醇和螺內酯(合併或不合並 MPA)用於 92 名女性傾向跨性別者的情況進行研究。其中,MPA 有兩種給藥方式:舌下含服 5~10 mg/天,或每三個月肌注 150 mg;接受 MPA 治療者有 39 人,其中 26 人(67%)報告乳房發育有所增長。論文雖未提供其餘細節,但可以認為其中對乳房發育的評價源自患者口述,主觀因素較大。
Igo & Visram (2021) 對在女性傾向跨性別者的激素療法中加用孕酮的情況進行研究。其中,孕酮以微粉化 100 mg 製劑(或為口服)的形式給藥;如患者主動要求,或患者表示對當前女性化和/或乳房發育效果不滿意,則給予孕酮。受試者共 190 人,其中 51 人(26.8%)接受孕酮治療。孕酮的初次給藥時間平均比雌二醇治療開始時要晚 12.7 個月;對激素治療的平均跟蹤時長為 14.3 個月。在服用孕酮的個體中,僅 6 人(11.8%)報告孕酮對乳房發育有益。論文雖未提供其餘細節,但和其它研究類似的是,其中對乳房發育效果的量化很可能也依賴於口述的自發報告。
綜上,這兩項研究顯然均未對乳房發育進行任何客觀評價,也未設置對照組以比較,故其結果的參考價值有限。

Nolan 及其同行則對正平穩接受激素治療的女性傾向跨性別者加用低劑量口服微粉化孕酮,並就該形式的孕酮對乳房發育的短期影響進行研究(Nolan et al., 2022a; Nolan et al., 2022b)。其中,23 名女性傾向跨性別者給予孕酮 100 mg/天,持續三個月;其結果與由 19 名女性傾向跨性別者構成的對照組進行比較。乳房發育效果通過患者報告的 Tanner 發育階段進行評價,具體為患者從各個 Tanner 階段的照片中選擇一張上報。
治療三個月後,兩組報告的 Tanner 階段無統計意義的差異(孕酮組平均值 3.5,95% 置信區間 3.2~3.7;對照組平均值 3.6,95% 置信區間 3.3~3.9;P = 0.42)。該研究存在一項侷限性,即口服孕酮的生物利用度極低,在 100 mg/天劑量下,其僅可產生很低的孕酮水平,遠低於黃體期正常範圍(Aly, 2018)。因此,在這項研究以及 Igo & Visram (2021) 的研究中,孕激素暴露很可能是不充分的。
除孕激素作用強度以外,該研究在方法上的侷限性還有:研究時長非常短(僅三個月);研究依賴於有主觀性的 Tanner 階段自發報告,而非較客觀的乳房外圍測量。無論如何,該研究從質量而言仍高於前述研究,且將來還有繼續研究並提供更長跟蹤期之結果的可能性。

前述研究之外,還有一批研究報告了雌激素和 CPA 用於女性傾向跨性別者時的乳房發育情況,其中大多采用較客觀的外圍測量手段(如乳房體積乳房—胸部高差、乳房罩杯和乳房半圍等);但因缺乏各組之間的比較,故本章節不作贅述。(下文對其作了簡要探討。)無論如何,從這批研究的結果可以發現,女性傾向跨性別者的乳房發育大多不良,這令人遺憾。

由於方法上的侷限性,前述研究的質量很不理想:例如,未設置對照組,未隨機分配受試者,依賴於低可信度手段(如主觀評價和自發報告)以評價乳房發育情況,治療時長過短,樣本規模過小,等等。由此,以上研究中互相矛盾的結論或許都有了解釋。
對於孕激素在女性傾向跨性別者中如何影響乳房發育,還需更多研究佐證。一份有關用於女性傾向跨性別者的激素治療、於 2014 年發表的評述,彙總了(當時)對孕激素和女性傾向跨性別者之乳房發育的研究情況(Wierckx, Gooren, & T’Sjoen, 2014)

我們對跨性別女性乳房發育的自然史,以及受不同跨性別激素療法有何影響的認識嚴重不足,且證據質量欠佳。目前的證據未證實孕激素用於跨性別女性可促進乳房發育,也不能證實這個作用不存在。因此,我們目前無法得出任何明確結論;這也表明尚需更多研究以釐清這些問題。

所幸,目前已有多項針對孕酮和其它孕激素用於女性傾向跨性別者的研究陸續進行。其中包括:

  1. 由 Sandeep Dhindsa 博士及其同行於美國密蘇里州聖路易斯市進行的,有關口服孕酮用於激素治療的一項隨機對照試驗(ClinicalTrials.gov; MediFind; ICH GCP)
  2. 由 Ada Cheung 及其同行於澳大利亞墨爾本進行的,有關口服孕酮用於激素治療的多項前瞻性 觀察性研究以及一項隨機對照試驗(University of Melbourne; University of Melbourne)
  3. 由 Ada Cheung 及其同行於澳大利亞墨爾本進行的,有關雌二醇—螺內酯複方和雌二醇—CPA 複方之對比的一項隨機對照試驗(ANZCTR; WHO ICTRP; Trans Health Research [傳單] [海報]; University of Melbourne)
  4. 由 Martin den Heijer 及其同行於荷蘭阿姆斯特丹自由大學醫學中心(VUMC)進行的,有關不同劑量的口服孕酮用於激素治療的一項大型隨機對照試驗(彙總資料和鏈接; 資料單荷蘭語原文; 資料單英譯文)

但遺憾的是,以上研究所用孕酮均以口服給藥,而此用途在生物利用度和效力上存在很大問題(Aly, 2018)。不過,據聞 VUMC 的研究者有意開展後續試驗,對其它途徑給藥的孕酮進行研究(彙總資料和鏈接)

女性正常青春期內的孕酮及其在乳房發育過程中的作用

要回答孕酮在乳房發育過程中起何等作用,以及孕酮在女性化激素治療中是否有助於乳房發育,不妨參考順性別女性經歷青春期時的正常生理狀況。順性別女孩平均會經歷 3~4 年的青春期,但大部分女孩可能會經歷 2~6 年。在有排卵月經週期開始前,孕酮一般維持於低位。初潮——即第一次月經和月經週期的開始——通常出現於 Tanner 四期,但也有相當一部分女孩在 Tanner 三期或五期(乳房發育完成時)經歷初潮(Marshall & Tanner, 1969; Marshall, 1978; Hillard, 2007)。因此,相當一部分女孩在經歷初潮或孕酮開始分泌之前便已達到 Tanner 五期(乳房發育完成);這表明對一部分女孩而言,孕酮並非使乳房達到 Tanner 五期的必要條件。整個乳房發育過程平均持續約 3.5 年,其中 Tanner 四期平均持續 2.5 年。綜上,在女性正常青春期當中,孕酮分泌是相對較晚的事件之一(Marshall, 1978; Begley, Firth, & Hoult, 1980; Drife, 1986)

在青春期,女孩的生殖軸尚未成熟(Rosenfield, 2013; Gunn et al., 2018; Carlson & Shaw, 2019; Sun et al., 2019)。初潮後一至兩年內,月經週期大多無排卵(Döring, 1963 [表格]; Apter, 1980; Lemarchand-Béraud et al., 1982; Talbert et al., 1985; Venturoli et al., 1987; Rosenfield, 2013; Gunn et al., 2018; Carlson & Shaw, 2019)。不排卵的情況下,卵泡(格氏囊)不會破裂形成黃體,從而不會開始孕酮的分泌。在 Tanner 五期之前,有排卵的月經週期僅佔半數左右(Talbert et al., 1985)。此外,初潮後一段時間裏月經週期是偏長的(如 50 天;成人為 28 天),故每年經歷的月經週期偏少(Rosenfield, 2013; Gunn et al., 2018; Carlson & Shaw, 2019)。相比成年人,已經歷初潮的青年人在黃體期的孕酮水平更低,即使排卵後亦然(McArthur, 1966 [圖例]; Lemarchand-Béraud et al., 1982; Apter et al., 1987; Venturoli et al., 1987; Venturoli et al., 1989; Sun et al., 2019)。從而,即使到青春期晚期,孕酮暴露仍是散發且有限的。
還有,這種情況不僅發生於 Tanner 五期之前,還會在之後發生。初潮後,月經週期趨於成熟並持續排卵需六年以上的時間(Lemarchand-Béraud et al., 1982; Venturoli et al., 1987; Carlson & Shaw, 2019)。此期間,有排卵的週期佔比逐漸上升,直至接近 100%(Lemarchand-Béraud et al., 1982; Venturoli et al., 1987; Carlson & Shaw, 2019)。在此之後,孕酮暴露方可完全達到成年水平(Lemarchand-Béraud et al., 1982; Venturoli et al., 1987)。有多項研究提供了青春期不同發育階段或年齡的孕酮水平,顯示出在此期間的孕酮暴露之低(例如 Sizonenko, 1978 [圖表]; Lee, 2001 [表格]; Aly, 2020)

綜上所述,孕酮分泌是在女性正常青春期當中較晚出現的事件;即使開始分泌,孕酮暴露也是散發且有限的,並一直持續到青春期結束之後;一部分女孩在孕酮分泌開始前便已完成乳房發育。以上事實使得孕酮在女性青春期乳房發育過程中的作用受到了懷疑。

動物中孕酮和乳腺發育的關係

動物青春期乳腺發育

雌性小鼠 * 中,敲除 孕酮受體導致生育力完全喪失,卵巢、子宮、生殖行為功能重度受損(Lydon et al., 1995; Ismail et al., 2003)。但截然不同的是,被敲除孕酮受體的小鼠在青春期的乳腺導管發育正常,形態學上與正常小鼠並無實際差異(Ismail et al., 2003)。而被敲除雌激素受體 α 的小鼠則有相反的表現,其青春期乳腺發育完全停止(Ismail et al., 2003; 維基百科; 維基百科)
然而,後續研究表明,雌性小鼠在無孕酮分泌、無孕酮受體或給予孕酮受體拮抗劑的情況下,實際上出現了乳腺導管推遲發育的情況(Shi, Lydon, & Zhang, 2004)。換言之,孕酮在青春期可刺激並加速乳腺導管發育,從而在青春期乳腺早期發育當中具備明顯的生理作用。孕酮對乳腺導管發育的刺激作用應是通過引誘乳腺導管和尾結表達雙調蛋白而介導的(Kariagina et al., 2010; Aupperlee et al., 2013);雙調蛋白作為表皮生長因子受體(EGFR)的激動劑,是青春期由雌激素引誘表達、介導乳腺發育的主要生長因子(Ciarloni, Mallepell, & Brisken, 2007; LaMarca & Rosen, 2007; McBryan et al., 2008)。然而,由於無孕酮參與的青春期乳腺導管發育只是被延遲、而會逐漸完成,故而有觀點認為,孕酮在小鼠的青春期乳腺發育過程中是可有可無的(Ismail et al., 2003)

* 譯者注:原文為 rice(大米),或為筆誤。

乳腺結構和乳腺小葉容積

孕激素主要參與乳腺小泡、小葉的發育。這類發育主要發生於妊娠期間,為泌乳和哺乳所需。乳房主要由兩種組織構成:一是上皮組織,包含導管和小葉/小泡等,是實際意義上的乳腺組織;二是間質組織,包括結締組織、脂肪組織等。小泡/小葉發育則是指小泡和小葉的增生和成熟,是上皮或腺體組織發育的一種形式。
在未妊娠或泌乳的婦女中,上皮組織僅佔乳房體積的 5~20% 左右,其餘 80~95% 均由間質組織構成(Hutson, Cowen, & Bird, 1985; Drife, 1986; Bryant et al., 1998; Gertig et al., 1999; Howard & Gusterson, 2000; Cline & Wood, 2006; Lorincz & Sukumar, 2006; Wilson et al., 2006; Xu et al., 2010; Pandya & Moore, 2011; Hagisawa, Shimura, & Arisaka, 2012; Sandhu et al., 2016; Rosenfield, Cooke, & Radovick, 2021)。具體而言,一項研究結果顯示,育齡婦女的乳房有約 10~20% 為上皮組織;脂肪組織約佔 10~35%;結締組織約佔 60~80%(Hutson, Cowen, & Bird, 1985; Wilson et al., 2006)。類似地,在患有乳房肥大的婦女中,乳腺組織僅佔乳房的一小部分(如 1~7%)(Bames, 1948; Cruz-Korchin et al., 2001)
但在妊娠和泌乳期間,乳房結構有大幅改變,上皮組織佔比大幅增加(Ramsay et al., 2005; Bland, Copeland, & Klimberg, 2018)。實際上,有資料顯示在妊娠和泌乳期間,乳房大部分由乳腺組織構成;一項針對泌乳婦女的研究中,乳腺組織構成了其乳房的 63%(範圍 46~83%)(Ramsay et al., 2005)
無論如何,在通常的生理條件和孕酮暴露下,乳腺小泡/小葉組織在乳房中的佔比是很小的。同時,由孕激素介導的乳腺小葉增長對於乳房體積的重要性並不明確,尚且存疑(Wierkcx, Gooren, & T’Sjoen, 2014)

完全性雄激素不敏感綜合徵、孕酮和乳房發育的關係

有觀點認為,孕酮可幫助順性別女性和女性傾向跨性別者的乳房從 Tanner 四期發展到五期,使乳房更為豐滿(例如 Prior, 2011; Prior, 2019a; Prior, 2020)。在跨性別網絡社羣中也有人認為,對於患有完全性雄激素不敏感綜合徵(CAIS)的順性別女性,因無孕酮分泌,其乳房發育停滯於 Tanner 四期,乳房“如錐形”。但事實上,當前尚無明確證據表明孕酮對於青春期乳房正常發育過程是必要的,也無證據表明其對於達到 Tanner 五期和乳房的豐滿是有益的。另外,以上觀點和多份文獻和證據南轅北轍,其中也包括 CAIS 女性本身。

CAIS 是指婦女的核型為 46,XY(即遺傳學上屬於“男性”),且有睾丸,但由於編碼雄激素受體的基因變異,其對雄激素完全脱敏,從而未能像男性一樣發育。CAIS 女性的激素由睾丸分泌,處於男性典型狀態;其中有處於男性正常偏高水平的睾酮,處於女性正常偏低水平、但足夠多的雌二醇,以及極低的孕酮分泌和孕酮水平。 從外表看,CAIS 女性並不像男性,而是徹徹底底的女性形態;其體型如正常女性,有陰道和乳房(維基百科; 照片)。其體內的睾酮無法促成男性化,而不受抑制的雌二醇則可促成女性化。CAIS 女性的生殖系統和發育不良的男性類同,其有睾丸而無卵巢、子宮和輸卵管。其陰道通常偏淺,內端閉合,無宮頸,這與子宮的缺失相關。

文獻上,患有 CAIS 的女性之乳房發育情況被描述為“良好”“較佳”“正常”“完全”“發育狀況較好”“豐滿”“普遍高於平均水平”“很大”,甚至是“豐滿撩人(voluptuous)”(Morris, 1953; Hertz et al., 1966; Valentine, 1969; Adams et al., 1970; Polani, 1970; Weisberg, Malkasian, & Pratt, 1970; Dewhurst, 1971; Perez-Palacios & Jaffe, 1972; Glenn, 1976; Dewhurst & Spence, 1977; Rutgers & Scully, 1991; Patterson, McPhaul, & Hughes, 1994; Quigley et al., 1995; McPhaul, 2002; Galani et al., 2008; Oakes et al., 2008; Tiefenbacher & Daxenbichler, 2008; Barbieri, 2017)
婦科專家 John McLean Morris 曾於 1953 年回顧並總結當時關於 CAIS 女性的既有科學文獻(共 82 個病例)並將該症狀描述為“有睾丸的女性化”(現已棄用),他將這批女性的乳房描述為“不尋常的大”“體積很大”(Morris, 1953; Quigley et al., 1995)。在他著名的 1953 年評述中還提到,她們的乳房“和正常女性一致,大多趨於過度發育”(Morris, 1953)。但實際上,有的 CAIS 女性乳房偏大,有的則偏小(Wisniewski et al., 2000);我們尚無明確資料證明其乳房體積是否確實大於平均水平。
從 CAIS 女性觀察到的乳房發育之差異,和在一般原生婦女當中觀察到的乳房體積之巨大差異是一致的。此相冊收集了文獻上公開的病例報告和評述所附 CAIS 女性及其乳房發育的照片。從中可以看出,CAIS 女性的乳房發育正常且較佳,但乳房體積和形狀在不同個體間有較大差異,這和一般女性相似。

CAIS 女性的乳房從未被描述成“錐形”“尖狀”或其它不規則形狀。只有一種例外,就是其乳暈/乳頭常被描述為“稚嫩(juvenile)”——或相對“小”“顏色淺”(例如此照片(見於 Morris, 1953; Morris & Mahesh, 1963; Khoo & Mackay, 1972; Perez-Palacios & Jaffe, 1972; Dewhurst & Spence, 1977; 等等)。這可能是因為 CAIS 女性的雌二醇水平平均僅有 35 pg/mL 左右(表格),而雌激素可引導乳頭、乳暈增大和色素沉積,且與劑量相關(Davis et al., 1945; Kennedy & Nathanson, 1953)。因此,要讓乳頭、乳暈和成人一樣完全成熟,可能需更高的雌激素水平。

此外,CAIS 女性的乳房並非僅可發育到 Tanner 四期;其會像正常女性一樣達到 Tanner 五期(Quigley, 1988; Quigley et al., 1995; Fortner, 2007; Cheikhelard et al., 2008; Ramos et al., 2018)。以下為相關文獻的摘錄(Quigley et al., 1995)

患有完全性[雄激素不敏感綜合徵(AIS)]的個體在青春期有較佳的女性化效果,乳房發育正常或偏大,面色光滑、無痤瘡。乳房和身形的女性化是在無雄激素抑制的情況下,對雌激素反饋的結果(雌激素主要源自睾丸,少量源自外周雄激素的芳香化)。……
在所有類型的 AIS 中,均可見乳房發育,程度介於輕度男性乳房增生和完全的 Tanner 五期女性乳房之間,且 AIS 程度越高,乳房發育越趨於明顯。

這裏“程度更高的 AIS”是指 CAIS,即此類綜合徵的完全形態,和不完全(部分輕度表徵)的雄激素不敏感綜合徵(AIS)相對(Quigley, 1988)。這是一種譜系疾病,只有“程度最高”的 CAIS 患者會對雄激素經受體介導的作用完全不敏感,也只有她們會有完全女性化的身體。不過,即使是部分性雄激素不敏感綜合徵(PAIS)也會讓患者有相當程度的乳房發育(例如 Saito et al., 2014; Lee et al., 2015)

如上文所述,之所以提及 CAIS 女性,是因為其睾丸不能分泌孕酮,從而使得孕酮水平非常低、以至可忽略不計(<2 ng/mL)(表格; Barbieri, 2017)。CAIS 女性相關的證據表明,——當下這可能是現有證據中最有説服力的一種——要達到正常或完全的乳房發育效果,是無需孕酮參與的(Barbieri, 2017)

作為大自然的一次基因實驗,雄激素不敏感綜合徵 為雌激素和雄激素對於乳房增長之調節的重大相互作用提供了一種臨牀參考。38 遺傳學男性(46,XY)在雄激素受體(AR)突變導致雄激素不敏感的情況下,體內 AR 無一可正常工作;儘管睾丸可產生睾酮,但其靶組織無法對較高水平的循環雄激素做出響應。此類綜合徵患者的循環雌二醇濃度約為 50 pg/mL,相當於女性卵泡早期的水平。 雄激素不敏感個體的乳房體積通常高於平均水平。 這表明,在雄激素完全失去抑制作用的情況下,中等水平的雌二醇足以引起明顯的乳房增長。在無 AR 的個體中,孕酮水平處於低位;這表明乳房體積並不一定依賴於孕酮的刺激作用。

據稱 CAIS 女性雖多有較大的乳房,但乳腺組織較小(相對於脂肪和結締組織),乳腺小泡/小葉幾乎未發育(Morris, 1953; Morris & Mahesh, 1963; Simmer, Pion, & Dignam, 1965; McMillan, 1966; Perez-Palacios & Jaffe, 1972; Dewhurst & Spence, 1977; Shapiro, 1982)。這可能與孕酮的缺乏有關,因為孕酮會參與乳腺小泡/小葉的發育成熟。值得一提的是,一般婦女羣體中的乳房大部分由間質脂肪和結締組織構成(約 80~90%),而非乳腺組織(10~20%)(維基百科);此外,當乳腺小泡/小葉發育時(例如妊娠期間),其會取代間質組織(Alex, Bhandary, & McGuire, 2020)。因此,更高的乳腺或小泡/小葉組織佔比不一定會使得乳房體積更大,這點在 CAIS 女性身上顯而易見。
還有,儘管乳房發育良好,但 CAIS 女性從未有任何乳腺癌報告(Aly, 2020a; Aly, 2020b)。這可能和以下因素有關:1) 缺乏孕酮;2) 乳腺小泡/小葉未發育成熟;3) 缺少第二條 X 染色體(Aly, 2020a; Aly, 2020b)

孕激素早期暴露和乳房發育不理想的潛在關係

已有文獻指出,孕激素早期、過早暴露可能導致乳房發育不理想。動物研究發現,在高劑量下,孕酮、醋酸氯地孕酮(一種和 CPA 有高度聯繫的人工孕激素)等孕激素的早期/過早暴露會使得兔的乳房發育不理想,但低劑量下則不然(Lyons & McGinty, 1941; Beyer, Cruz, & Martinez-Manautou, 1970)
除動物研究外,已有多份臨牀著述警告稱,順性別女孩和女性傾向跨性別者早期/過早暴露於孕激素,可能導致乳房發育不理想(Zacharin, 2000; Bondy et al., 2007; Colvin, Devineni, & Ashraf, 2014; Wierckx, Gooren, & T’Sjoen, 2014; Kaiser & Ho, 2015; Bauman, Novello, & Kreitzer, 2016; Gawlik et al., 2016; Randolph, 2018; Donaldson et al., 2019; Heath & Wynne, 2019a; Heath & Wynne, 2019b; Iwamoto et al., 2019; Crowley & Pitteloud, 2020; Naseem, Lokman, & Fitzgerald, 2021; Federici et al., 2022; Lucien et al., 2022; Rothman & Iwamoto, 2022)。以上信源的相關片段可於此處查閲。與此相關,對青春期推遲的女孩進行青春期誘導治療時,孕激素僅當在以雌激素治療約 2~3 年之後才加入,此時一般認為乳房發育趨於完成。

然而,不同物種的乳腺發育和對激素的反饋是有差異的;對於諸臨牀著述的觀點,尚無任何實打實的數據或證據可以證實。因此,尚不清楚人類早期暴露於孕激素是否會導致乳房發育不理想。另外,即使這是真的,所需孕激素暴露量之多少也不清楚。不過,有多個研究領域是和這個問題相關的,包括:孕激素在乳房中表達的抗雌激素作用;臨牀研究中,雌激素和 CPA(一種強效孕激素)用於女性傾向跨性別者時對乳房發育之影響;病例報告中,孕激素用於治療順性別婦女乳房肥大;理論上,缺乏 17α-羥化酶/17,20-裂解酶的順性別女孩乳房發育不良可能和較高的孕酮暴露有關;等等。下面會對此做詳細討論。

孕激素在乳房中表達的抗雌激素作用

已知孕激素在子宮、陰道和宮頸等組織內具有很強的抗雌激素作用(維基百科)。因為這點,孕激素被引入到更年期激素治療,以預防子宮內膜增生子宮內膜癌——而不受控的雌激素治療會有這方面的風險(維基百科)。在乳房,孕激素似乎也有抗雌激素作用(Mauvais-Jarvis, Kuttenn, & Gompel, 1986; Mauvais-Jarvis, Kuttenn, & Gompel, 1987; Mauvais-Jarvis et al., 1987; Kuttenn et al., 1994; Wren & Eden, 1996; Plu-Bureau, Touraine, & Mauvais-Jarvis, 1999; 維基百科)。其作用可能包括:

臨牀研究發現,將外用孕酮直接用於乳房,可抑制雌激素介導的乳腺細胞增生;但這可能是因為對乳房局部給予了超生理水平的孕酮(Barrat et al., 1990; Chang et al., 1995; Foidart et al., 1996; Spicer, Ursin, & Pike, 1996; Foidart et al., 1998; de Lignières, 2002; Gompel & Plu-Bureau, 2018; Trabert et al., 2020)。與此相關的是,孕激素被認為可有效治療乳房疼痛乳腺結節乳腺纖維囊性病變等雌激素依賴性良性乳房疾病(Mauvais-Jarvis, Sitruk-Ware, & Kuttenn, 1981; Winkler et al., 2001; Schindler, 2011; 維基百科; 維基百科; 維基百科)。通過孕激素在乳房中的抗雌激素作用,孕激素是有可能限制雌激素介導的乳房發育的。

醋酸環丙孕酮用於女性傾向跨性別者時對乳房發育的影響

對於孕激素抑制乳房發育的可能性,CPA 是尤其需要注意的。這是因為,CPA 不僅是一種抗雄激素製劑,還是一種強效孕激素;其為女性傾向跨性別者所用的劑量可導致非常高的孕激素暴露量(Aly, 2019)。在有關雌激素和 CPA 用於女性傾向跨性別者的研究中,乳房發育往往不甚理想(Kanhai et al., 1999; Sosa et al., 2003; Sosa et al., 2004; Wierckx et al., 2014; Fisher et al., 2016; Tack et al., 2017; de Blok et al., 2018; Reisman, Goldstein, & Safer, 2019; de Blok et al., 2020; Meyer et al., 2020)。然而,女性傾向跨性別者或許只是普遍有不良的乳房發育,而不一定與 CPA 或孕激素暴露有關。事實上,在一項研究中,先接受青春期抑制治療(估計採用 GnRH 激動劑)、後接受激素治療的女性傾向跨性別者,也和成人一樣有不良的乳房發育(Boogers et al., 2022)
有一項關於雌二醇—螺內酯複方、雌二醇—CPA 複方用於女性傾向跨性別者時的乳房發育情況的研究,目前正在澳大利亞進行;其有望為這個問題提供更多見解(ANZCTR)

用於乳房肥大的孕激素治療

有人認為,低孕酮水平可能是導致青春期乳房肥大的因素之一(Sun et al., 2018)。多份已發表的病例報告系列病例研究都有孕激素用於治療青春期乳房肥大的記錄(Sperling & Gold, 1973; Boyce, Hoffman, & Mathes, 1984; Ryan & Pernoll, 1985; Gliosci & Presutti, 1993; Sridhar & Jaya Sinha, 1995; Baker et al., 2001; Dancey et al., 2008; Bland, Howard, Romrell, 2009; Hoppe et al., 2011; Sun et al., 2018);其中,地屈孕酮和 MPA 等孕激素被假定在乳房有抗雌激素作用,而被用以嘗試阻止或減緩乳房增長。在這批數目有限的病例中,治療有效性不盡相同。由於青春期乳房肥大可自愈(即乳房發育會逐漸自行停止),且研究方法存在侷限性,故難以從這批報告得出可靠的結論。

17α-羥化酶/17,20-裂解酶不足所致的乳房發育不良

已有 17α-羥化酶/17,20-裂解酶不足的女孩接受雌激素治療後出現乳房發育不良的報告;同時,高孕酮水平的早期暴露被猜測是僅次於此狀況的原因(Turan et al., 2009; Athanasoulia et al., 2013; Deeb et al., 2015; Çamtosun et al., 2017; Fernández-Cancio et al., 2017; Kardelen et al., 2018)。然而,這僅僅出於理論,目前尚無證據表明孕酮與乳房發育不良存在明確因果關係。

另見

參考文獻

  • Adams, R. D., Kliman, B., Federman, D. D., Ulfelder, H. S., & Holmes, L. B. (1970). Syndromes of Testicular Feminization. Clinical Pediatrics, 9(3), 165–178. [DOI:10.1177/000992287000900312]
  • Alex, A., Bhandary, E., & McGuire, K. P. (2020). Diseases of the Breast during Pregnancy and Lactation. In Alipour, S., & Omranipour, R. (Eds.). Diseases of the Breast during Pregnancy and Lactation (Advances in Experimental Medicine and Biology, Volume 1252). Cham: Springer International Publishing. [DOI:10.1007/978-3-030-41596-9]
  • Apter, D. (1980). Serum steroids and pituitary hormones in female puberty: a partly longitudinal study. Clinical Endocrinology, 12(2), 107–120. [DOI:10.1111/j.1365-2265.1980.tb02125.x]
  • Apter, D., Räisänen, I., Ylöstalo, P., & Vihko, R. (1987). Follicular growth in relation to serum hormonal patterns in adolescent compared with adult menstrual cycles. Fertility and Sterility, 47(1), 82–88. [DOI:10.1016/s0015-0282(16)49940-1]
  • Athanasoulia, A., Auer, M., Riepe, F., & Stalla, G. (2013). Rare Missense P450c17 (CYP17A1) Mutation in Exon 1 as a Cause of 46,XY Disorder of Sexual Development: Implications of Breast Tissue ‘Unresponsiveness’ despite Adequate Estradiol Substitution. Sexual Development, 7(4), 212–215. [DOI:10.1159/000348301]
  • Aupperlee, M. D., Leipprandt, J. R., Bennett, J. M., Schwartz, R. C., & Haslam, S. Z. (2013). Amphiregulin mediates progesterone-induced mammary ductal development during puberty. Breast Cancer Research, 15(3), R44. [DOI:10.1186/bcr3431]
  • Baker, S. B., Burkey, B. A., Thornton, P., & LaRossa, D. (2001). Juvenile Gigantomastia: Presentation of Four Cases and Review of the Literature. Annals of Plastic Surgery, 46(5), 517–526. [DOI:10.1097/00000637-200105000-00011]
  • Bames, H. O. (1948). Reduction of massive breast hypertrophy. Plastic and Reconstructive Surgery, 3(5), 560–569. [DOI:10.1097/00006534-194809000-00006]
  • Barbieri, R. L. (2019). Breast. In Strauss, J. F., & Barbieri, R. L. (Eds.). Yen and Jaffe’s Reproductive Endocrinology: Physiology, Pathophysiology, and Clinical Management, 8th Edition (pp. 248–255.e3). Philadelphia: Elsevier. [Google 閲讀] [DOI:10.1016/B978-0-323-47912-7.00010-X]
  • Barrat, J., de Lignières, B., Marpeau, L., Larue, L., Fournier, S., Nahoul, K., Linares, G., Giorgi, H., & Contesso, G. (1990). Effet in vivo de l’administration locale de progestérone sur l’activité mitotique des galactophores humains. Résultat d’une étude pilote. [The in vivo effect of the local administration of progesterone on the mitotic activity of human ductal breast tissue. Results of a pilot study.] Journal de Gynecologie, Obstetrique et Biologie de la Reproduction, 19(3), 269–274. [Google 學術 1] [Google 學術 2] [PubMed]
  • Bässler, R. (1970). The Morphology of Hormone Induced Structural Changes in the Female Breast. In Altmann, H.-W., et al. (Eds.). Current Topics in Pathology: Ergebnisse der Pathology, Volume 53 (pp. 1–89). Heidelberg: Springer Berlin. [DOI:10.1007/978-3-662-30514-0_1] [PDF] ——譯者注:未發現原文有引用
  • Bauman, A., Novello, L., & Kreitzer, P. (2016). Endocrine Disorders and Delayed Puberty. In Appelbaum, H. (Ed.). Abnormal Female Puberty: A Clinical Casebook (pp. 87–107). Cham: Springer. [DOI:10.1007/978-3-319-27225-2_5]
  • Begley, D. J., Firth, J. A., & Hoult, J. R. (1980). The Breast and Lactation. In Begley, D. J., Firth, J. A., & Hoult, J. R. Human Reproduction and Developmental Biology (pp. 204–219). London: Macmillan Education UK. [DOI:10.1007/978-1-349-16260-4_14]
  • Beyer, C., Cruz, M. L., & Martinez-Manautou, J. (1970). Effect of Chlormadinone Acetate on Mammary Development and Lactation in the Rabbit. Endocrinology, 86(5), 1172–1174. [DOI:10.1210/endo-86-5-1172]
  • Bland, K. I., Copeland, E. M., & Klimberg, V. S. (2018). Anatomy of the Breast, Axilla, Chest Wall, and Related Metastatic Sites. In Bland, K. I., Copeland, E. M., Klimberg, V. S., Gradishar, W. J., White, J., & Korourian, S. (Eds.). The Breast: Comprehensive Management of Benign and Malignant Diseases, 5th Edition (pp. 20–36.e2). Philadelphia: Elsevier. [DOI:10.1016/b978-0-323-35955-9.00002-7]
  • Bland, K. I., Harrison Howard, J., & Romrell, L. J. (2009). Congenital and Acquired Disturbances of Breast Development and Growth. In Bland, K. I., & Copeland, E. M. (Eds.). The Breast: Comprehensive Management of Benign and Malignant Diseases, 4th Edition (pp. 189–207). Philadelphia: Saunders/Elsevier. [Google 學術] [Google 閲讀] [OpenLibrary] [WorldCat]
  • Bondy, C. A., & Turner Syndrome Consensus Study Group. (2007). Care of girls and women with Turner syndrome: a guideline of the Turner Syndrome Study Group. The Journal of Clinical Endocrinology & Metabolism, 92(1), 10–25. [DOI:10.1210/jc.2006-1374]
  • Boogers, L., Infirri, S. S., Bouchareb, A., de Blok, C., Liberton, N., van Trotsenburg, P., Dreijerink, K., den Heijer, M., Wiepjes, C., & Hannema, S. (2022). The effect of timing of puberty suppression on breast development in trans girls; a cross-sectional study. Hormone Research in Paediatrics, 95(Suppl 2) [60th Annual Meeting of the European Society for Paediatric Endocrinology (ESPE), Rome, Italy, September 15–17, 2022], 390–391 (abstract no. P1-379). [Google 學術] [DOI:10.1159/000525606] [URL] [PDF 1] [PDF 2]
  • Boyce, S. W., Hoffman, P. G., & Mathes, S. J. (1984). Recurrent Macromastia after Subcutaneous Mastectomy. Annals of Plastic Surgery, 13(6), 511–518. [DOI:10.1097/00000637-198412000-00008]
  • Bryant, R., Underwood, A., Robinson, A., Stephenson, T., & Underwood, J. (1998). Determination of breast tissue composition for improved accuracy in estimating radiation doses and risks in mammographic screening. The Breast, 7(2), 95–98. [DOI:10.1016/s0960-9776(98)90064-9]
  • Çamtosun, E., Şıklar, Z., Ceylaner, S., Kocaay, P., & Berberoğlu, M. (2017). Delayed Diagnosis of a 17-Hydroxylase/17,20-Lyase Deficient Patient Presenting as a 46,XY Female: A Low Normal Potassium Level Can Be an Alerting Diagnostic Sign. Journal of Clinical Research in Pediatric Endocrinology, 9(2), 163–167. [DOI:10.4274/jcrpe.3839]
  • Carlson, L. J., & Shaw, N. D. (2019). Development of Ovulatory Menstrual Cycles in Adolescent Girls. Journal of Pediatric and Adolescent Gynecology, 32(3), 249–253. [DOI:10.1016/j.jpag.2019.02.119]
  • Chang, K., Lee, T. T., Linares-Cruz, G., Fournier, S., & de Ligniéres, B. (1995). Influences of percutaneous administration of estradiol and progesterone on human breast epithelial cell cycle in vivo. Fertility and Sterility, 63(4), 785–791. [DOI:10.1016/s0015-0282(16)57482-2]
  • Cheikhelard, A., Morel, Y., Thibaud, E., Lortat-Jacob, S., Jaubert, F., Polak, M., & Nihoul-Fekete, C. (2008). Long-Term Followup and Comparison Between Genotype and Phenotype in 29 Cases of Complete Androgen Insensitivity Syndrome. Journal of Urology, 180(4), 1496–1501. [DOI:10.1016/j.juro.2008.06.045]
  • Ciarloni, L., Mallepell, S., & Brisken, C. (2007). Amphiregulin is an essential mediator of estrogen receptor α function in mammary gland development. Proceedings of the National Academy of Sciences, 104(13), 5455–5460. [DOI:10.1073/pnas.0611647104]
  • Cline, J. M., & Wood, C. E. (2006). Hormonal Effects on the Mammary Gland of Postmenopausal Nonhuman Primates. Breast Disease, 24(1), 59–70. [DOI:10.3233/bd-2006-24105]
  • Colvin, C., Devineni, G., & Ashraf, A. P. (2014). Delayed Puberty. In Bandeira, F., Gharib, H., Golbert, A., Griz, L., & Faria, M. (Eds.). Endocrinology and Diabetes (pp. 203–217). New York: Springer. [DOI:10.1007/978-1-4614-8684-8_17]
  • Crowley, W. F., & Pitteloud, N. (2020). Approach to the patient with delayed puberty. UpToDate. [Google 學術] [URL]
  • Cruz-Korchin, N., Korchin, L., González-Keelan, C., Climent, C., & Morales, I. (2002). Macromastia. Plastic and Reconstructive Surgery, 109(1), 64–68. [DOI:10.1097/00006534-200201000-00011]
  • de Blok, C. J., Dijkman, B. A., Wiepjes, C. M., Staphorsius, A. S., Timmermans, F. W., Smit, J. M., Dreijerink, K. M., & den Heijer, M. (2020). Sustained Breast Development and Breast Anthropometric Changes in 3 Years of Gender-Affirming Hormone Treatment. The Journal of Clinical Endocrinology & Metabolism, 106(2), e782–e790. [DOI:10.1210/clinem/dgaa841]
  • de Blok, C. J., Klaver, M., Wiepjes, C. M., Nota, N. M., Heijboer, A. C., Fisher, A. D., Schreiner, T., T’Sjoen, G., & den Heijer, M. (2017). Breast Development in Transwomen After 1 Year of Cross-Sex Hormone Therapy: Results of a Prospective Multicenter Study. The Journal of Clinical Endocrinology & Metabolism, 103(2), 532–538. [DOI:10.1210/jc.2017-01927]
  • de Lignières, B. (2002). Effects of progestogens on the postmenopausal breast. Climacteric, 5(3), 229–235. [DOI:10.1080/cmt.5.3.229.235]
  • Dancey, A., Khan, M., Dawson, J., & Peart, F. (2008). Gigantomastia – a classification and review of the literature. Journal of Plastic, Reconstructive & Aesthetic Surgery, 61(5), 493–502. [DOI:10.1016/j.bjps.2007.10.041]
  • Davis, M. E., Boynton, M. W., Ferguson, J. H., & Rothman, S. (1945). Studies on Pigmentation of Endocrine Origin. The Journal of Clinical Endocrinology & Metabolism, 5(3), 138–146. [DOI:10.1210/jcem-5-3-138]
  • Deeb, A., Al Suwaidi, H., Attia, S., & Al Ameri, A. (2015). 17-hydroxylase/17,20-lyase deficiency due to a R96Q mutation causing hypertension and poor breast development. Endocrinology, Diabetes & Metabolism Case Reports, 2015(1), 15-0069. [DOI:10.1530/EDM-15-0069]
  • Dewhurst, C. (1971). The XY female. American Journal of Obstetrics and Gynecology, 109(5), 675–688. [DOI:10.1016/0002-9378(71)90753-8]
  • Dewhurst, C., & Spence, J. E. (1977). The XY female. British Journal of Hospital Medicine, 17(5), 498, 501–506. [Google 學術] [PubMed] [PDF]
  • Dittrich, R., Binder, H., Cupisti, S., Hoffmann, I., Beckmann, M., & Mueller, A. (2005). Endocrine Treatment of Male-to-Female Transsexuals Using Gonadotropin-Releasing Hormone Agonist. Experimental and Clinical Endocrinology & Diabetes113(10), 586–592. [DOI:10.1055/s-2005-865900]
  • Donaldson, M., Kriström, B., Ankarberg-Lindgren, C., Verlinde, S., van Alfen-van der Velden, J., Gawlik, A., van Gelder, M., Sas, T., & (2019). Optimal Pubertal Induction in Girls with Turner Syndrome Using Either Oral or Transdermal Estradiol: A Proposed Modern Strategy. Hormone Research in Paediatrics, 91(3), 153–163. [DOI:10.1159/000500050]
  • Drife, J. O. (1986). Breast Development in Puberty. Annals of the New York Academy of Sciences, 464(1) [Endocrinology of the Breast: Basic and Clinical Aspects], 58–65. [DOI:10.1111/j.1749-6632.1986.tb15993.x]
  • Döring, G. K. (1963). Über die relative Häufigkeit des anovulatorischen Cyclus im Leben der Frau. Archiv für Gynäkologie, 199(2), 115–123. [DOI:10.1007/bf00668062]
  • Federici, S., Goggi, G., Quinton, R., Giovanelli, L., Persani, L., Cangiano, B., & Bonomi, M. (2021). New and Consolidated Therapeutic Options for Pubertal Induction in Hypogonadism: In-depth Review of the Literature. Endocrine Reviews, 43(5), 824–851. [DOI:10.1210/endrev/bnab043]
  • Fernández-Cancio, M., García-García, E., González-Cejudo, C., Martínez-Maestre, M., Mangas-Cruz, M., Guerra-Junior, G., Pandi de Mello, M., Arnhold, I. J., Nishi, M. Y., Bilharinho Mendonça, B., García-Arumí, E., Audí, L., Tizzano, E., & Carrascosa, A. (2017). Discordant Genotypic Sex and Phenotype Variations in Two Spanish Siblings with 17α-Hydroxylase/17,20-Lyase Deficiency Carrying the Most Prevalent Mutated CYP17A1 Alleles of Brazilian Patients. Sexual Development, 11(2), 70–77. [DOI:10.1159/000468160]
  • Finkenzeller, D. A., & Loveless, M. B. (2007). Pediatric Gynecology. In Fortner, K. B., Szymanski, L. M., Fox, H. E., & Wallach, E. E. (Eds.). The Johns Hopkins Manual of Gynecology and Obstetrics, 3rd Edition (Spiral Manual Series) (pp. 363–379). Philadelphia: Lippincott Williams & Wilkins. [Google 學術] [Google 閲讀] [OpenLibrary] [WorldCat] [Archive.org]
  • Fisher, A. D., Castellini, G., Ristori, J., Casale, H., Cassioli, E., Sensi, C., Fanni, E., Amato, A. M., Bettini, E., Mosconi, M., Dèttore, D., Ricca, V., & Maggi, M. (2016). Cross-Sex Hormone Treatment and Psychobiological Changes in Transsexual Persons: Two-Year Follow-Up Data. The Journal of Clinical Endocrinology & Metabolism, 101(11), 4260–4269. [DOI:10.1210/jc.2016-1276]
  • Foidart, J. M., Colin, C., Denoo, X., Desreux, J., Fournier, S., & de Linières, B. (1996). Influence of percutaneous administration of estradiol and progesterone on the proliferation of human breast epithelial cells. In Calvo, F., Crépin, M., & Magdelenat, H. (Eds.). Breast Cancer. Advances in Biology and Therapuetics. John Libbey Eurotext, 329–334. [Google 學術] [Google 閲讀]
  • Foidart, J., Colin, C., Denoo, X., Desreux, J., Béliard, A., Fournier, S., & de Lignières, B. (1998). Estradiol and Progesterone Regulate the Proliferation of Human Breast Epithelial Cells. Fertility and Sterility, 69(5), 963–969. [DOI:10.1016/s0015-0282(98)00042-9]
  • Galani, A., Kitsiou-Tzeli, S., Sofokleous, C., Kanavakis, E., & Kalpini-Mavrou, A. (2008). Androgen insensitivity syndrome: clinical features and molecular defects. Hormones, 7(3), 217–229. [DOI:10.14310/horm.2002.1201]
  • Gawlik, A., Hankus, M., Such, K., Drosdzol-Cop, A., Madej, P., Borkowska, M., Zachurzok, A., & Malecka-Tendera, E. (2016). Hypogonadism and Sex Steroid Replacement Therapy in Girls with Turner Syndrome. Journal of Pediatric and Adolescent Gynecology, 29(6), 542–550. [DOI:10.1016/j.jpag.2016.03.005]
  • Gertig, D. M., Stillman, I. E., Byrne, C., Spiegelman, D., Schnitt, S. J., Connolly, J. L., Colditz, G. A., & Hunter, D. J. (1999). Association of age and reproductive factors with benign breast tissue composition. Cancer Epidemiology, Biomarkers & Prevention8(10), 873–879. [Google 學術] [PubMed] [URL]
  • Glenn, J. F. (1976). Testicular feminization syndrome current clinical considerations. Urology, 7(6), 569–577. [DOI:10.1016/0090-4295(76)90079-0]
  • Gliosci, A., & Presutti, F. (1993). Virginal gigantomastia: Validity of combined surgical and hormonal treatments. Aesthetic Plastic Surgery, 17(1), 61–65. [DOI:10.1007/bf00455051]
  • Gompel, A., & Plu-Bureau, G. (2018). Progesterone, progestins and the breast in menopause treatment. Climacteric, 21(4), 326–332. [DOI:10.1080/13697137.2018.1476483]
  • Gunn, H. M., Tsai, M., McRae, A., & Steinbeck, K. S. (2018). Menstrual Patterns in the First Gynecological Year: A Systematic Review. Journal of Pediatric and Adolescent Gynecology, 31(6), 557–565.e6. [DOI:10.1016/j.jpag.2018.07.009]
  • Hagisawa, S., Shimura, N., & Arisaka, O. (2012). Effect of Excess Estrogen on Breast and External Genitalia Development in Growth Hormone Deficiency. Journal of Pediatric and Adolescent Gynecology, 25(3), e61–e63. [DOI:10.1016/j.jpag.2011.11.005]
  • Heald, F. P. (Ed.). (1966). Adolescent Gynecology. Baltimore: Williams & Wilkins. [Google 學術] [Google 閲讀] [OpenLibrary] [WorldCat] ——譯者注:原文引用為“McArthur, 1966”
  • Heath, R. A., & Wynne, K. (2019). Children and Adolescents. In Heath, R. A., & Wynne, K. A Guide to Transgender Health: State-of-the-art Information for Gender-Affirming People and Their Supporters (pp. 87–106). Santa Barbara: Praeger/ABC-CLIO. [Google 閲讀]
  • Heath, R. A., & Wynne, K. (2019). Hormone and Surgical Therapies for Adults. In Heath, R. A., & Wynne, K. A Guide to Transgender Health: State-of-the-art Information for Gender-Affirming People and Their Supporters (pp. 107–146). Santa Barbara: Praeger/ABC-CLIO. [Google 閲讀]
  • Hertz, R., Odell, W. D., & Ross, G. T. (1966). Diagnostic Implications of Primary Amenorrhea: Combined Clinical Staff Conference at the National Institutes of Health. Annals of Internal Medicine, 65(4), 800–820. [DOI:10.7326/0003-4819-65-4-800]
  • Hillard, P. J. A. (2007). Benign Diseases of the Female Reproductive Tract. In Berek, J. S., & Novak, E. (Eds.). Berek & Novak’s Gynecology, 14th Edition (pp. 431–496). Philadelphia: Lippincott Williams and Wilkins, 431–496. [Google 學術] [OpenLibrary] [WorldCat] [Archive.org]
  • Hoppe, I. C., Patel, P. P., Singer-Granick, C. J., & Granick, M. S. (2011). Virginal Mammary Hypertrophy: A Meta-Analysis and Treatment Algorithm. Plastic and Reconstructive Surgery, 127(6), 2224–2231. [DOI:10.1097/prs.0b013e3182131bd1]
  • Howard, B. A., & Gusterson, B. A. (2000). Human Breast Development. Journal of Mammary Gland Biology and Neoplasia, 5(2), 119–137. [DOI:10.1023/a:1026487120779]
  • Hutson, S. W., Cowen, P. N., & Bird, C. C. (1985). Morphometric studies of age related changes in normal human breast and their significance for evolution of mammary cancer. Journal of Clinical Pathology, 38(3), 281–287. [DOI:10.1136/jcp.38.3.281]
  • Igo, J., & Visram, H. (2021). Progesterone Therapy Use and Safety in Male to Female Transgender Patients. Canadian Journal of Diabetes, 45(7 Suppl), S39–S39 (abstract no. 109). [DOI:10.1016/j.jcjd.2021.09.119]
  • Ismail, P. M., Amato, P., Soyal, S. M., DeMayo, F. J., Conneely, O. M., O’Malley, B. W., & Lydon, J. P. (2003). Progesterone involvement in breast development and tumorigenesis—as revealed by progesterone receptor “knockout” and “knockin” mouse models. Steroids, 68(10–13), 779–787. [DOI:10.1016/s0039-128x(03)00133-8]
  • Iwamoto, S. J., Defreyne, J., Rothman, M. S., Van Schuylenbergh, J., Van de Bruaene, L., Motmans, J., & T’Sjoen, G. (2019). Health considerations for transgender women and remaining unknowns: a narrative review. Therapeutic Advances in Endocrinology and Metabolism, 10, 204201881987116. [DOI:10.1177/2042018819871166]
  • Jain, J., Kwan, D., & Forcier, M. (2019). Medroxyprogesterone Acetate in Gender-Affirming Therapy for Transwomen: Results From a Retrospective Study. The Journal of Clinical Endocrinology & Metabolism104(11), 5148–5156. [DOI:10.1210/jc.2018-02253]
  • Kaiser, U., & Ho, K. K. (2015). Pituitary Physiology and Diagnostic Evaluation. In Melmed, S., Polonsky, K. S., Larsen, P. R., Kronenberg, & H. M. (Eds.). Williams Textbook of Endocrinology, 13th Edition (pp. 176–231). Philadelphia: Elsevier. [DOI:10.1016/B978-0-323-29738-7.00008-3] [Google 閲讀]
  • Kanhai, R. C., Hage, J. J., Asscheman, H., Mulder, W. J., & Hage, J. J. (1999). Augmentation Mammaplasty in Male-to-Female Transsexuals. Plastic and Reconstructive Surgery, 104(2), 542–549. [DOI:10.1097/00006534-199908000-00040]
  • Kanhai, R. C., Hage, J. J., van Diest, P. J., Bloemena, E., & Mulder, J. W. (2000). Short-Term and Long-Term Histologic Effects of Castration and Estrogen Treatment on Breast Tissue of 14 Male-to-Female Transsexuals in Comparison With Two Chemically Castrated Men. The American Journal of Surgical Pathology, 24(1), 74–80. [DOI:10.1097/00000478-200001000-00009]
  • Kardelen, A. D., Toksoy, G., Baş, F., Yavaş Abalı, Z., Gençay, G., Poyrazoğlu, Ş., Bundak, R., Altunoğlu, U., Avcı, Ş., Najaflı, A., Uyguner, O., Karaman, B., Başaran, S., & Darendeliler, F. (2018). A Rare Cause of Congenital Adrenal Hyperplasia: Clinical and Genetic Findings and Follow-up Characteristics of Six Patients with 17-Hydroxylase Deficiency Including Two Novel Mutations. Journal of Clinical Research in Pediatric Endocrinology, 10(3), 206–215. [DOI:10.4274/jcrpe.0032]
  • Kariagina, A., Xie, J., Leipprandt, J. R., & Haslam, S. Z. (2010). Amphiregulin Mediates Estrogen, Progesterone, and EGFR Signaling in the Normal Rat Mammary Gland and in Hormone-Dependent Rat Mammary Cancers. Hormones and Cancer, 1(5), 229–244. [DOI:10.1007/s12672-010-0048-0]
  • Kennedy, B. J. (1953). Effects of intensive sex steroid hormone therapy in advanced breast cancer. JAMA, 152(12), 1135–1141. [DOI:10.1001/jama.1953.63690120004013]
  • Khoo, S. K., & Mackay, E. V. (1972). Testicular Feminization: The Clinical Features, Endocrine Function and Gonadal Pathology in Six Patients. The Australian and New Zealand Journal of Obstetrics and Gynaecology, 12(1), 1–13. [DOI:10.1111/j.1479-828x.1972.tb00721.x]
  • Kutten, F., Malet, C., & Leygue, E. (1994). Antiestrogen action of progestogens in human breast cells. In Berg, G., & Hammar, M. (Eds.). The Modern Management of the Menopause: A Perspective for the 21st Century [The Proceedings of the VII International Congress on the Menopause, Stockholm, Sweden 1993] (pp. 419–433). Canforth: Parthenon. [Google 學術] [Google 閲讀] [OpenLibrary] [WorldCat] [Archive.org] [PDF] ——譯者注:原文引用為“Kuttenn et al., 1994”
  • LaMarca, H. L., & Rosen, J. M. (2007). Estrogen regulation of mammary gland development and breast cancer: amphiregulin takes center stage. Breast Cancer Research, 9(4), 304. [DOI:10.1186/bcr1740]
  • Lee, P. A. (2001). Physiology of Puberty. In Becker, K. L., Bilezikian, J. P., Bremner, W. J., Hung, W., Kahn, C. R., Loriaux, D. L., Nylén, E. S., Rebar, R. W., Robertson, G. L., Snider, R. H., Wartofsky, L. (Eds.). Principles and Practice of Endocrinology and Metabolism, 3rd Edition (pp. 885–893). Philadelphia: Lippincott Williams & Wilkins. [Google 學術] [Google 閲讀] [Archive.org] [OpenLibrary] [WorldCat]
  • Lee, S. W., Kwak, D. S., Jung, I. S., Kwak, J. H., Park, J. H., Hong, S. M., Lee, C. B., Park, Y. S., Kim, D. S., Choi, W. H., & Ahn, Y. H. (2015). Partial Androgen Insensitivity Syndrome Presenting with Gynecomastia. Endocrinology and Metabolism, 30(2), 226–230. [DOI:10.3803/enm.2015.30.2.226]
  • Lemarchand-Béraud, T., Zufferey, M., Reymond, M., & Rey, I. (1982). Maturation of the Hypothalamo-Pituitary-Ovarian Axis in Adolescent Girls. The Journal of Clinical Endocrinology & Metabolism, 54(2), 241–246. [DOI:10.1210/jcem-54-2-241]
  • Lorincz, A. M., & Sukumar, S. (2006). Molecular links between obesity and breast cancer. Endocrine-Related Cancer, 13(2), 279–292. [DOI:10.1677/erc.1.00729]
  • Lucien, J. N., Ortega, M. T., Calvert, M. E., Smith, C., White, X., Rogers, H., Mosley, B., Agrawal, R., Drude, A., McGee, C., George, M., Brown, A., Downey, K., Wild, C., Njunge, A., Kuzmiak, C. M., Zava, D., Zava, T., Pollard, J., Francis, J., Beery, B. L., Harlin, M., Gonzalez, G. R., & Shaw, N. D. (2022). The Launch of A Girl’s First Period Study: Demystifying Reproductive Hormone Profiles in Adolescent Girls. Journal of Pediatric and Adolescent Gynecology, 35(4), 420–425. [DOI:10.1016/j.jpag.2021.12.018]
  • Lydon, J. P., DeMayo, F. J., Funk, C. R., Mani, S. K., Hughes, A. R., Montgomery, C. A., Shyamala, G., Conneely, O. M., & O’Malley, B. W. (1995). Mice lacking progesterone receptor exhibit pleiotropic reproductive abnormalities.. Genes & Development, 9(18), 2266–2278. [DOI:10.1101/gad.9.18.2266]
  • Lyons, W. R., & McGinty, D. A. (1941). Effects of estrone and progesterone on male rabbit mammary glands. I. Varying doses of progesterone. Proceedings of the Society for Experimental Biology and Medicine, 48(1), 83–86. [DOI:10.3181/00379727-48-13227]
  • Malet, C., Gompel, A., Yaneva, H., Cren, H., Fidji, N., Mowszowicz, I., Kuttenn, F., & Mauvais-Jarvis, P. (1991). Estradiol and Progesterone Receptors in Cultured Normal Human Breast Epithelial Cells and Fibroblasts: Immunocytochemical Studies. The Journal of Clinical Endocrinology & Metabolism, 73(1), 8–17. [DOI:10.1210/jcem-73-1-8]
  • Marshall, W. A., & Tanner, J. M. (1969). Variations in pattern of pubertal changes in girls. Archives of Disease in Childhood, 44(235), 291–303. [DOI:10.1136/adc.44.235.291]
  • Marshall, W. A. (1978). Puberty. In Falkner, F., & Tanner, J. M. (Eds.). Human Growth: Postnatal Growth (pp. 141–181). Boston: Springer US. [DOI:10.1007/978-1-4684-2622-9_6]
  • Mauvais-Jarvis, P., Sitruk-Ware, R., & Kuttenn, F. (1981). Benign Breast Disease. In McGuire, W. L. (Ed.). Breast Cancer 4: Advances in Research and Treatment (pp. 51–94). Boston: Springer US. [DOI:10.1007/978-1-4615-6571-0_3]
  • Mauvais-Jarvis, P., Kuttenn, F., & Gompel, A. (1986). Antiestrogen action of progesterone in breast tissue. Breast Cancer Research and Treatment, 8(3), 179–188. [DOI:10.1007/bf01807330]
  • Mauvais-Jarvis, P., Kuttenn, F., & Gompel, A. (1987). Antiestrogen Action of Progesterone in Breast Tissue. Hormone Research, 28(2–4), 212–218. [DOI:10.1159/000180946]
  • Mauvais-Jarvis, P., Kuttenn, F., Gompel, A., & Benotmane, A. (1987). Action anti-estrogène de la progestérone dans le sein. [Antiestrogen action of progesterone in the breast]. Pathologie-Biologie, 35(7), 1081–1086. [Google 學術 1] [Google 學術 2] [PubMed]
  • McBryan, J., Howlin, J., Napoletano, S., & Martin, F. (2008). Amphiregulin: Role in Mammary Gland Development and Breast Cancer. Journal of Mammary Gland Biology and Neoplasia, 13(2), 159–169. [DOI:10.1007/s10911-008-9075-7]
  • McDonough, P. G., Spicer, D. V., Ursin, G., & Pike, M. C. (1996). Progesterone Concentrations—Physiologic or Pharmacologic? Fertility and Sterility, 65(5), 1077–1078. [DOI:10.1016/s0015-0282(16)58295-8]
  • McMillan, M. (1966). Five cases of testicular feminisation including one with a teratoma of the testis. The Journal of Pathology and Bacteriology, 91(2), 417–427. [DOI:10.1002/path.1700910216]
  • McPhaul, M. J. (2002). Androgen receptor mutations and androgen insensitivity. Molecular and Cellular Endocrinology, 198(1–2), 61–67. [DOI:10.1016/s0303-7207(02)00369-6]
  • Meyer, W. J., Finkelstein, J. W., Stuart, C. A., Webb, A., Smith, E. R., Payer, A. F., & Walker, P. A. (1981). Physical and hormonal evaluation of transsexual patients during hormonal therapy. Archives of Sexual Behavior10(4), 347–356. [DOI:10.1007/bf01565538]
  • Meyer, W. J., Webb, A., Stuart, C. A., Finkelstein, J. W., Lawrence, B., & Walker, P. A. (1986). Physical and hormonal evaluation of transsexual patients: A longitudinal study. Archives of Sexual Behavior15(2), 121–138. [DOI:10.1007/bf01542220]
  • Meyer, G., Mayer, M., Mondorf, A., Flügel, A. K., Herrmann, E., & Bojunga, J. (2020). Safety and rapid efficacy of guideline-based gender-affirming hormone therapy: an analysis of 388 individuals diagnosed with gender dysphoria. European Journal of Endocrinology, 182(2), 149–156. [DOI:10.1530/eje-19-0463]
  • Morris, J. M. (1953). The syndrome of testicular feminization in male pseudohermaphrodites. American Journal of Obstetrics and Gynecology, 65(6), 1192–1211. [DOI:10.1016/0002-9378(53)90359-7]
  • Morris, J. M., & Mahesh, V. B. (1963). Further observations on the syndrome, “testicular feminization”. American Journal of Obstetrics and Gynecology87(6), 731–748. [Google 學術 1] [Google 學術 2] [PubMed] [PDF]
  • Naseem, H., Lokman, M., & Fitzgerald, C. (2021). Management of congenital hypogonadotropic hypogonadism in females. Human Fertility, advance online publcation. [DOI:10.1080/14647273.2021.1998929]
  • Nolan, B. J., Frydman, A. S., Leemaqz, S. Y., Carroll, M., Grossmann, M., Zajac, J. D., & Cheung, A. S. (2022). Effects Of Low-dose Oral Micronised Progesterone On Sleep, Psychological Distress And Breast Development In Transgender Individuals Undergoing Feminising Hormone Therapy: A Prospective Controlled Study. Journal of the Endocrine Society6(Suppl 1), A653–A654 (abstract no. LBODP089). [DOI:10.1210/jendso/bvac150.1351]
  • Nolan, B. J., Frydman, A. S., Leemaqz, S. Y., Carroll, M., Grossmann, M., Zajac, J. D., & Cheung, A. S. (2022). Effects of low-dose oral micronised progesterone on sleep, psychological distress, and breast development in transgender individuals undergoing feminising hormone therapy: a prospective controlled study. Endocrine Connections, 11(5), e220170. [DOI:10.1530/EC-22-0170]
  • Oakes, M. B., Eyvazzadeh, A. D., Quint, E., & Smith, Y. R. (2008). Complete Androgen Insensitivity Syndrome—A Review. Journal of Pediatric and Adolescent Gynecology, 21(6), 305–310. [DOI:10.1016/j.jpag.2007.09.006]
  • Pandya, S., & Moore, R. G. (2011). Breast Development and Anatomy. Clinical Obstetrics & Gynecology54(1), 91–95. [DOI:10.1097/grf.0b013e318207ffe9]
  • Pasqualini, J. R. (2007). Progestins and breast cancer. Gynecological Endocrinology, 23(Suppl 1), 32–41. [DOI:10.1080/09513590701585003]
  • Pasqualini, J. R. (2009). Breast cancer and steroid metabolizing enzymes: The role of progestogens. Maturitas, 65(Suppl 1), S17–S21. [DOI:10.1016/j.maturitas.2009.11.006]
  • Patterson, M. N., McPhaul, M. J., & Hughes, I. A. (1994). Androgen insensitivity syndrome. Baillière’s Clinical Endocrinology and Metabolism, 8(2), 379–404. [DOI:10.1016/s0950-351x(05)80258-7]
  • Perez-Palacios, G., & Jaffe, R. B. (1972). The Syndrome of Testicular Feminization. Pediatric Clinics of North America, 19(3), 653–667. [DOI:10.1016/s0031-3955(16)32744-4]
  • Plu-Bureau, G., Touraine, P., & Mauvais-Jarvis, P. (1999). Interactions Between Estradiol and Progesterone in Normal Breast: Implications for Mammary Carcinogenesis. In Manni, A. (Ed.). Endocrinology of Breast Cancer (Contemporary Endocrinology, Volume 11) (pp. 21–37). Totowa, New Jersey: Humana Press. [DOI:10.1007/978-1-59259-699-7_2] [OpenLibrary] [Archive.org]
  • Polani, P. E. (1970). Hormonal and clinical aspects of hermaphroditism and the testicular feminizing syndrome in man. Philosophical Transactions of the Royal Society of London. B, Biological Sciences, 259(828), 187–206. [DOI:10.1098/rstb.1970.0058]
  • Prior, J. C., Vigna, Y. M., Watson, D., Diewold, P., & Robinow, O. (1986). Spironolactone in the presurgical therapy of male to female transsexuals: Philosophy and experience of the Vancouver Gender Dysphoria Clinic. Journal of Sex Information & Education Council of Canada, 1(1), 1–7. [Google 學術] [PDF]
  • Prior, J. C., Vigna, Y. M., & Watson, D. (1989). Spironolactone with physiological female steroids for presurgical therapy of male-to-female transsexualism. Archives of Sexual Behavior, 18(1), 49–57. [DOI:10.1007/bf01579291]
  • Prior J. C. (2011). Progesterone for Symptomatic Perimenopause Treatment - Progesterone politics, physiology and potential for perimenopause. Facts, Views & Vision in ObGyn, 3(2), 109–120. [PubMed] [PubMed Central] [PDF]
  • Prior, J. C. (2019). Progesterone is Important for Transwomen’s Therapy—Applying Evidence for the Benefits of Progesterone in Ciswomen. The Journal of Clinical Endocrinology & Metabolism, 104(4), 1181–1186, [DOI:10.1210/jc.2018-01777]
  • Prior, J. C. (2019). Response to Letter to the Editor: “Progesterone is Important for Transwomen’s Therapy—Applying Evidence for the Benefits of Progesterone in Ciswomen”, The Journal of Clinical Endocrinology & Metabolism, 104(8), 3129–3130. [DOI:10.1210/jc.2019-00524]
  • Prior, J. C. (2020). Women’s Reproductive System as Balanced Estradiol and Progesterone Actions—A revolutionary, paradigm-shifting concept in women’s health. Drug Discovery Today: Disease Models, 32(Part B), 31–40. [DOI:10.1016/j.ddmod.2020.11.005]
  • Ramsay, D. T., Kent, J. C., Hartmann, R. A., & Hartmann, P. E. (2005). Anatomy of the lactating human breast redefined with ultrasound imaging. Journal of Anatomy, 206(6), 525–534. [DOI:10.1111/j.1469-7580.2005.00417.x]
  • Rosenfield, R. L., Cooke, D. W., & Radovick, S. (2021). Puberty in the Female and Its Disorders. In Sperling, M. A., Majzoub, J. A., Menon, R. K., & Stratakis, C. A. (Eds.). Sperling Pediatric Endocrinology, 5th Edition (pp. 528–626). Philadelphia: Elsevier. [DOI:10.1016/B978-0-323-62520-3.00016-6]
  • Quigley, C. A., Bellis, A. D., Marschke, K. B., El-Awady, M. K., Wilson, E. M., & French, F. S. (1995). Androgen Receptor Defects: Historical, Clinical, and Molecular Perspectives. Endocrine Reviews, 16(3), 271–321. [DOI:10.1210/edrv-16-3-271]
  • Quigley, C. A. (1998). The androgen receptor: Physiology and pathophysiology. In Nieschlag, E., & Behre, H. M. (Eds.). Testosterone: Action · Deficiency · Substitution, 2nd Edition (pp. 33–106). Berlin/Heidelberg: Springer. [DOI:10.1007/978-3-642-72185-4_2]
  • Ramos, L., Chávez, B., Mares, L., Valdés, E., & Vilchis, F. (2018). Mutational analysis of the androgen receptor (NR3C4) gene in patients with 46,XY DSD. Gene, 641, 86–93. [DOI:10.1016/j.gene.2017.10.038]
  • Randolph, J. F. (2018). Gender-Affirming Hormone Therapy for Transgender Females. Clinical Obstetrics & Gynecology, 61(4), 705–721. [DOI:10.1097/grf.0000000000000396]
  • Reisman, T., Goldstein, Z., & Safer, J. D. (2019). A Review of Breast Development in Cisgender Women and Implications for Transgender Women. Endocrine Practice, 25(12), 1338–1345. [DOI:10.4158/ep-2019-0183]
  • Rosenfield, R. L. (2013). Adolescent Anovulation: Maturational Mechanisms and Implications. The Journal of Clinical Endocrinology & Metabolism, 98(9), 3572–3583. [DOI:10.1210/jc.2013-1770]
  • Rothman, M. S., & Iwamoto, S. J. (2022). Feminizing Gender-Affirming Hormone Therapy: Special Considerations for Older Adults. In Davis, T. F. (Ed.). A Case-Based Guide to Clinical Endocrinology (pp. 513–523). Cham: Springer International Publishing. [DOI:10.1007/978-3-030-84367-0_58]
  • Rutgers, J. L., & Scully, R. E. (1991). The Androgen Insensitivity Syndrome (Testicular Feminization). International Journal of Gynecological Pathology, 10(2), 126–144. [DOI:10.1097/00004347-199104000-00002]
  • Ryan, R. F., & Pernoll, M. L. (1985). Virginal Hypertrophy. Plastic and Reconstructive Surgery, 75(5), 737–742. [DOI:10.1097/00006534-198505000-00024]
  • Saito, R., Yamamoto, Y., Goto, M., Araki, S., Kubo, K., Kawagoe, R., Kawada, Y., Kusuhara, K., Igarashi, M., & Fukami, M. (2014). Tamoxifen Treatment for Pubertal Gynecomastia in Two Siblings with Partial Androgen Insensitivity Syndrome. Hormone Research in Paediatrics, 81(3), 211–216. [DOI:10.1159/000356923]
  • Sandhu, R., Chollet-Hinton, L., Kirk, E. L., Midkiff, B., & Troester, M. A. (2016). Digital histologic analysis reveals morphometric patterns of age-related involution in breast epithelium and stroma. Human Pathology, 48, 60–68. [DOI:10.1016/j.humpath.2015.09.031]
  • Schindler, A. E. (2010). Dydrogesterone and other progestins in benign breast disease: an overview. Archives of Gynecology and Obstetrics, 283(2), 369–371. [DOI:10.1007/s00404-010-1456-7]
  • Shapiro, L. R. (1982). Disorders of Female Sex Differentiation. In Blaustein, A. (Ed.). Pathology of the Female Genital Tract, 2nd Edition (pp. 479–510). New York: Springer New York. [DOI:10.1007/978-1-4757-1767-9_20]
  • Shi, H. Y., Lydon, J. P., & Zhang, M. (2004). Hormonal Defect in Maspin Heterozygous Mice Reveals a Role of Progesterone in Pubertal Ductal Development. Molecular Endocrinology, 18(9), 2196–2207. [DOI:10.1210/me.2004-0052]
  • Simmer, H. H., Pion, R. J., & Dignam, W. J. (1965). Testicular Feminization: Endocrine Function of Feminizing Testes, Comparison with Normal Testes. Springfield, Illinois: Thomas. [Google 學術] [Google 閲讀] [OpenLibrary] [WorldCat]
  • Sizonenko, P. C. (1978). Endocrinology in Preadolescents and Adolescents. American Journal of Diseases of Children132(7), 704–712. [DOI:10.1001/archpedi.1978.02120320064015]
  • Sosa, M., Jódar, E., Arbelo, E., Domínguez, C., Saavedra, P., Torres, A., Salido, E., de Tejada, M. J., & Hernández, D. (2003). Bone Mass, Bone Turnover, Vitamin D, and Estrogen Receptor Gene Polymorphisms in Male to Female Transsexuals. Journal of Clinical Densitometry, 6(3), 297–304. [DOI:10.1385/jcd:6:3:297]
  • Sosa, M., Jódar, E., Arbelo, E., Domı́nguez, C., Saavedra, P., Torres, A., Salido, E., Limiñana, J., Gómez de Tejada, M. J., & Hernández, D. (2004). Serum lipids and estrogen receptor gene polymorphisms in male-to-female transsexuals: effects of estrogen treatment. European Journal of Internal Medicine, 15(4), 231–237. [DOI:10.1016/j.ejim.2004.04.009]
  • Sperling, R. L., & Gold, J. J. (1973). Use of an anti-estrogen after a reduction mammaplasty to prevent recurrence of virginal hypertrophy of breasts. Plastic and Reconstructive Surgery, 52(4), 439–442. [DOI:10.1097/00006534-197352040-00030]
  • Sridhar, G. R., & Sinha, M. J. (1995). Macromastia in adolescent girls. Indian Pediatrics, 32(4), 496–499. [Google 學術] [PubMed] [PDF]
  • Sun, B. Z., Kangarloo, T., Adams, J. M., Sluss, P. M., Welt, C. K., Chandler, D. W., Zava, D. T., McGrath, J. A., Umbach, D. M., Hall, J. E., & Shaw, N. D. (2018). Healthy Post-Menarchal Adolescent Girls Demonstrate Multi-Level Reproductive Axis Immaturity. The Journal of Clinical Endocrinology & Metabolism, 104(2), 613–623. [DOI:10.1210/jc.2018-00595]
  • Sun, S. X., Bostanci, Z., Kass, R. B., Mancino, A. T., Rosenbloom, A. L., Klimberg, V. S., & Bland, K. I. (2018). Breast Physiology: Normal and Abnormal Development and Function. In Bland, K. I., Copeland, E. M., Klimberg, V. S., Gradishar, W. J., White, J., & Korourian, S. (Eds.). The Breast: Comprehensive Management of Benign and Malignant Diseases, 5th Edition (pp. 37–56.e6). Philadelphia: Elsevier. [DOI:10.1016/b978-0-323-35955-9.00003-9]
  • Tack, L. J., Heyse, R., Craen, M., Dhondt, K., Bossche, H. V., Laridaen, J., & Cools, M. (2017). Consecutive Cyproterone Acetate and Estradiol Treatment in Late-Pubertal Transgender Female Adolescents. The Journal of Sexual Medicine, 14(5), 747–757. [DOI:10.1016/j.jsxm.2017.03.251]
  • Talbert, L. M., Hammond, M. G., Groff, T., & Udry, J. R. (1985). Relationship of age and pubertal development to ovulation in adolescent girls. Obstetrics & Gynecology, 66(4), 542–544. [Google 學術] [URL]
  • Tiefenbacher, K., & Daxenbichler, G. (2008). The Role of Androgens in Normal and Malignant Breast Tissue. Breast Care, 3(5), 325–331. [DOI:10.1159/000158055]
  • Trabert, B., Sherman, M. E., Kannan, N., & Stanczyk, F. Z. (2019). Progesterone and Breast Cancer. Endocrine Reviews, 41(2), 320–344. [DOI:10.1210/endrev/bnz001]
  • Turan, S., Bereket, A., Guran, T., Akcay, T., Papari-Zareei, M., & Auchus, R. J. (2009). Puberty in a case with novel 17-hydroxylase mutation and the putative role of estrogen in development of pubic hair. European Journal of Endocrinology, 160(2), 325–330. [DOI:10.1530/eje-08-0632]
  • Valentine, G. H. (1969). The Chromosome Disorders: An Introduction for Clinicians, 2nd Edition. London: W. Heinemann Medical Books. [Google 學術] [Google 閲讀] [OpenLibrary] [WorldCat] [Archive.org]
  • Venturoli, S., Porcu, E., Fabbri, R., Magrini, O., Paradisi, R., Pallotti, G., Gammi, L., & Flamigni, C. (1987). Postmenarchal evolution of endocrine pattern and ovarian aspects in adolescents with menstrual irregularities. Fertility and Sterility, 48(1), 78–85. [DOI:10.1016/s0015-0282(16)59294-2]
  • Venturoli, S., Fabbri, R., Porcu, E., Paradisi, R., Orsini, L. F., Brondelli, L., Ruggeri, S., & Flamigni, C. (1989). Endocrine and ovarian parameters at various frequencies of ovulation in adolescents. Archives of Gynecology and Obstetrics, 246(2), 107–114. [DOI:10.1007/bf00934127]
  • Weisberg, M. G., Malkasian, G. D., & Pratt, J. H. (1970). Testicular feminization syndrome. American Journal of Obstetrics and Gynecology, 107(8), 1181–1187. [DOI:10.1016/s0002-9378(15)30367-7]
  • Wierckx, K., Gooren, L., & T’Sjoen, G. (2014). Clinical Review: Breast Development in Trans Women Receiving Cross-Sex Hormones. The Journal of Sexual Medicine, 11(5), 1240–1247. [DOI:10.1111/jsm.12487]
  • Wierckx, K., Van Caenegem, E., Schreiner, T., Haraldsen, I., Fisher, A., Toye, K., Kaufman, J. M., & T’Sjoen, G. (2014). Cross‐Sex Hormone Therapy in Trans Persons Is Safe and Effective at Short‐Time Follow‐Up: Results from the European Network for the Investigation of Gender Incongruence. The Journal of Sexual Medicine, 11(8), 1999–2011. [DOI:10.1111/jsm.12571]
  • Wilson, C. L., Sims, A. H., Howell, A., Miller, C. J., & Clarke, R. B. (2006). Effects of oestrogen on gene expression in epithelium and stroma of normal human breast tissue. Endocrine-Related Cancer, 13(2), 617–628. [DOI:10.1677/erc.1.01165]
  • Winkler, U. H., Schindler, A. E., Brinkmann, U. S., Ebert, C., & Oberhoff, C. (2001). Cyclic progestin therapy for the management of mastopathy and mastodynia. Gynecological Endocrinology, 15(Suppl 6), 37–43. [DOI:10.1080/gye.15.s6.37.43]
  • Wisniewski, A. B., Migeon, C. J., Meyer-Bahlburg, H. F., Gearhart, J. P., Berkovitz, G. D., Brown, T. R., & Money, J. (2000). Complete Androgen Insensitivity Syndrome: Long-Term Medical, Surgical, and Psychosexual Outcome. The Journal of Clinical Endocrinology & Metabolism, 85(8), 2664–2669. [DOI:10.1210/jcem.85.8.6742]
  • Wren, B. G., & Eden, J. A. (1996). Do Progestogens Reduce The Risk of Breast Cancer? A Review of the Evidence. Menopause, 3(1), 4–12. [DOI:10.1097/00042192-199603010-00003]
  • Xu, P., Ye, W., Zhong, S., Li, H., Feng, E., Lin, S. H., Kuo, C. T., Liu, J. Y., & Lin, Y. C. (2010). Leptin and zeranol up-regulate cyclin D1 expression in primary cultured normal human breast pre-adipocytes. Molecular Medicine Reports3(6), 983–990. [DOI:10.3892/mmr.2010.370]
  • Zacharin, M. (2000). Use of androgens and oestrogens in adolescents - A review of hormone replacement treatment. Journal of Pediatric Endocrinology and Metabolism, 13(1), 3–12. [DOI:10.1515/JPEM.2000.13.1.3]

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