diff --git a/content/articles/cpa-dosage.md b/content/articles/cpa-dosage.md index 4f1d879..031b108 100644 --- a/content/articles/cpa-dosage.md +++ b/content/articles/cpa-dosage.md @@ -4,8 +4,8 @@ linkTitle: 低剂量醋酸环丙孕酮足可高效抑制睾酮 description: 本文探讨了以更低剂量服用 CPA，并深入论证了低剂量的合理性。 author: Aly published: 2019-07-01 -updated: 2023-03-31 -translated: 2023-04-05 +updated: 2024-03-30 +translated: 2024-10-27 translators: - Bersella AI tags: @@ -127,7 +127,7 @@ CPA 是一种强效孕激素，当用于顺性别妇女时，1 mg/天的剂量 多项研究中，将雌二醇与高剂量 CPA（50–100 mg/天）合并用于女性倾向跨性别者时，其将睾酮水平抑制到了女性正常范围内（50 ng/dL 或 1.7 nmol/L 以下）([Giltay & Gooren, 2000][GG00]; [Giltay et al., 2000][G00]; [Giltay et al., 2003][G03]; [Giltay et al., 2004][G04]; [Toorians et al., 2003][T03]; [T’Sjoen et al., 2005][TS05]; [Slagter et al., 2006][S06]; [T’Sjoen et al., 2009][TS09]; [Ott et al., 2011][O11]; [Wierckx et al., 2012][W12]; [Wierckx et al., 2014][W14]; [Zubiaurre-Elorza et al., 2014][ZE14]; [Fuss et al., 2015][F15]; [Van Caenegem et al., 2015][VC15]; [Gava et al., 2016][G16]; [Bultynck et al., 2017][B17]; [Fung, Hellstern-Layefsky, & Lega, 2017][FHL17]; [Kranz et al., 2017][K17]; [Tack et al., 2017][T17]; [Wiepjes et al., 2017][W17]; [de Blok et al., 2018][DB17]; [Defreyne et al., 2018][D18]; [Vita et al., 2018][V18]; [Angus et al., 2019][A19]; [Chen et al., 2019][C19]; [Scharff et al., 2019][S19]; [van Dijk et al., 2019][VD19]; [van Velzen et al., 2019][VV19]; [Vereecke, 2019][V19]; [Vlot et al., 2019][VLOT19]; [Wiepjes et al., 2019][W19]; [Kranz, Kaufmann, & Lanzenberger, 2020][KKL20]; [Meyer et al., 2020][M20]; [Gava et al., 2020][G20]; [Sofer et al., 2020][S20]; [Vereecke et al., 2021][V21])。 -1980 和 1990 年代，针对前列腺癌患者的临床研究发现，将高剂量孕激素（例如每日 100–300 mg 的 CPA、或 40–160 mg 的[醋酸甲地孕酮][wiki12]）结合低剂量雌激素（例如每日 0.1–0.2 mg 的[己烯雌酚][wiki14]、或 0.5–1.5 mg 的雌二醇）使用，可完全抑制性腺的睾酮分泌，并将睾酮水平降至去势后的范围（小于 50 ng/dL）([Geller et al., 1981a][G81a]; [Geller et al., 1981b][G81b]; [Geller & Albert, 1983][GA83]; [Goldenberg et al., 1988][G88]; [Johnson et al., 1988][J88]; [Geller, 1988][GEL88]; [Venner et al., 1988][V88]; [Geller, 1991][G91-PDF]; [Goldenberg & Bruchovsky, 1991][GB91]; [Bruchovsky et al., 1993][B93]; [Goldenberg et al., 1996][G96])。与此类似，一份 1989 年的病例系列报告也披露，有 3 名女性倾向跨性别者在以 100 mg/天的 CPA 合并较低剂量雌激素治疗后，取得了同样疗效([Jequier, Bullimore, & Bishop, 1989][JBB89])。\ +1980 和 1990 年代，针对前列腺癌患者的临床研究发现，将高剂量孕激素（例如每日 100–300 mg 的 CPA、或 40–160 mg 的[醋酸甲地孕酮][wiki12]）结合低剂量雌激素（例如每日 0.1–0.2 mg 的[己烯雌酚][wiki14]、或 0.5–1.5 mg 的雌二醇）使用，可完全抑制性腺的睾酮分泌，并将睾酮水平降至去势后的范围（小于 50 ng/dL）([Geller et al., 1981a][G81a]; [Geller et al., 1981b][G81b]; [Geller & Albert, 1983][GA83]; [Goldenberg et al., 1988][G88]; [Johnson et al., 1988][J88]; [Geller, 1988][GEL88]; [Venner et al., 1988][V88]; [Geller, 1991][G91]; [Goldenberg & Bruchovsky, 1991][GB91]; [Bruchovsky et al., 1993][B93]; [Goldenberg et al., 1996][G96])。与此类似，一份 1989 年的病例系列报告也披露，有 3 名女性倾向跨性别者在以 100 mg/天的 CPA 合并较低剂量雌激素治疗后，取得了同样疗效([Jequier, Bullimore, & Bishop, 1989][JBB89])。\ 这里有一篇文献摘录对 CPA 用于前列腺癌治疗的情况做了详述： > 如前所述，CPA 并未完全抑制血浆睾酮浓度：其被抑制了 70% 左右，但数值仍相当于去势后浓度的三倍。为系统研究该问题，Rennie 等 (59) 调查并对比了 12 种睾酮除去法。他们发现，将 CPA 与极低剂量的己烯雌酚（0.1 mg/天）合用，可高效去除雄激素（例如血浆睾酮、组织内的双氢睾酮）。该团队随后还发现，每日 200mg、甚至 100mg 的 CPA 足以获得相似的内分泌反馈，这也和其第二阶段临床治疗的相当正面的反馈具有关联性 (60,61)。从内分泌学视角而言，这项研究法不仅具有较多潜在优势，而且逻辑性很强：这种给药方案可结合两种制剂的抗雄效果；仅需少量雌激素，即可将血浆睾酮水平降低至经过去势的程度。一旦睾酮达到去势后水平，只需少量 CPA 即可中和剩余雄激素（主要来自肾上腺）的作用。在第三阶段疗程里，并未将合用低剂量 CPA 及己烯雌酚的疗法，与常规疗法进行比较。考虑到现有内分泌反馈与观察结果，二者合用的疗法应该具有相对其它常规疗法的竞争力。([Schröder & Radlmaier, 2002][SR02]) @@ -329,9 +329,37 @@ CPA 剂量,不服用,10 mg/天,25 mg/天,50 mg/天,100 mg/天 论文作者指出，在本研究中，接受激素治疗的女性倾向跨性别者的睾酮水平，与顺性别妇女接近或稍低于之。 +### 后记六：Warzywoda 等人 (2024) 的 GoLoCypro 研究报告 {#update-6-warzywoda-et-al-2024-golocypro-study} + +2024 年二月，由 Judith Dean 及同行进行的 GoLoCypro 研究被在线发表： + +- Warzywoda, S., Fowler, J. A., Wood, P., Bisshop, F., Russell, D., Luu, H., Kelly, M., Featherstone, V., & Dean, J. A. (2024). How low can you go? Titrating the lowest effective dose of cyproterone acetate for transgender and gender diverse people who request feminizing hormones. *International Journal of Transgender Health*, advance online publication. \[DOI:[10.1080/26895269.2024.2317395][W24]] + +其中部分片段摘录如下： + +> 完成试验的受试者中，有 74.0%（34/46）的睾酮水平达到了目标范围（0.5～1.5 nmol/L），有 41.3%（19/46）的 CPA 剂量被滴定到最低值（每周两次 12.5 mg 环丙孕酮）。 + +> 绝大多数（91.30%，42/46）完成试验的受试者的 CPA 剂量处于第三阶梯（每日 12.5 mg 或隔日 25 mg）或以下，其中 69.0%（29/42）的睾酮水平达到目标范围；此外，完成试验的受试者有 41.3%（19/46）服用最低剂量（每周两次 12.5 mg 环丙孕酮），其中 57.9%（11/19）的睾酮水平达到目标范围。 + +> 研究结果显示，对于部分患者，隔日 12.5 mg 或以下的 CPA 剂量成功地将睾酮降至绝经前范围，且没有过度抑制之。 + +> 本研究发现，可采取低于标准剂量（每日 12.5 mg 或隔日 25 mg）的 CPA 来抑制睾酮。有多项研究支持此法，其中发现用于接受女性化激素治疗之个体的 CPA 在较低剂量下（10 mg/天）可有效降低睾酮([Even Zohar et al., 2021][EZ21]; [Kuijpers et al., 2021][K21])。在本研究中，尽管并非所有受试者均得以下调 CPA 剂量，但完成试验的受试者有四分之一在每周两次 12.5 mg（等效于 3.5 mg/天）的 CPA 剂量下达成了目标睾酮范围。据我们所知，本研究首度揭示了低于 10 mg/天、隔日或每周两次剂量下的 CPA 对降低睾酮并维持于目标范围具有临床有效性。 + +### 后记七：2023～2024 年新发表的低剂量 CPA 相关研究 {#update-7-more-new-low-dose-cpa-studies-20232024} + +2023 至 2024 年间新发表的、有关低剂量 CPA 用于女性倾向跨性别者的研究有： + +- Angus, L. M., Leemaqz, S., Zajac, J. D., & Cheung, A. S. (November 2023). A randomised controlled trial of spironolactone versus cyproterone in trans people commencing estradiol. *AusPATH 2023 Symposium*. \[[URL][A23A]] \[[PDF][A23A-PDF]] \[[跨性别健康研究小组博客文章][A23A-THR]] +- Angus, L. M., Leemaqz, S. Y., Zajac, J. D., & Cheung, A. S. (November 2023). The effect of cyproterone and spironolactone on breast development in transgender women: a randomised controlled trial. *ESA/SRB/ENSA 2023 ASM 26-29 November, Brisbane*, 54–55 (abstract no. 132). \[[URL][A23B]] \[[PDF][A23B-PDF]] \[[摘要全文][A23B-EXC]] \[[跨性别健康研究小组博客文章][A23B-THR]] +- Flamant, T., Vervalcke, J., & T’Sjoen, G. (November 2023). Dose Reduction of Cyproterone Acetate in Trans Women and the Effect on Patient-reported Outcomes: Results from the ENIGI Study. *Endocrine Abstracts*, *97* \[*Belgian Endocrine Society 2023*], 5–5 (abstract no. 007). \[[URL][FVT23]] \[[PDF][FVT23-PDF]] +- Korpaisarn, S., Arunakul, J., Chaisuksombat, K., & Rattananukrom, T. (2023). A Low Dose Cyproterone Acetate In Feminizing Hormone Treatment. *Journal of the Endocrine Society*, *7*(Suppl 1), A1098–A1099 (abstract no. SAT397/bvad114.2068). \[DOI:[10.1210/jendso/bvad114.2068][K23]] +- Yang, W., Hong, T., Chang, X., Han, M., Gao, H., Pan, B., Zhao, Z., & Liu, Y. (2024). The efficacy of and user satisfaction with different antiandrogens in Chinese transgender women. *International Journal of Transgender Health*, advance online publication. \[DOI:[10.1080/26895269.2024.2323514][Y24]] + ## 参考文献 {#references} - Angus, L., Leemaqz, S., Ooi, O., Cundill, P., Silberstein, N., Locke, P., Zajac, J. D., & Cheung, A. S. (2019). 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Effects of Cross-Sex Hormone Treatment on Cortical Thickness in Transsexual Individuals. *The Journal of Sexual Medicine*, *11*(5), 1248–1261. \[DOI:[10.1111/jsm.12491][ZE14]] @@ -457,6 +489,7 @@ CPA 剂量,不服用,10 mg/天,25 mg/天,50 mg/天,100 mg/天 2023 年 3 月 29 日,更新诸后记标题。 2023 年 4 月 4 日,第三次修订，增补“表一”和诸表格标题，更新个别叙述，添加相关文献。 2023 年 6 月 29 日,更正“己烯雌酚”译名。 +2024 年 10 月 27 日,第四次修订，增补后记六、七，更新参考文献和链接。 ``` @@ -478,7 +511,7 @@ CPA 剂量,不服用,10 mg/天,25 mg/天,50 mg/天,100 mg/天 [table3]: https://en.wikipedia.org/wiki/Template:Published_case_reports_of_cyproterone_acetate-associated_prolactinoma [table4]: https://en.wikipedia.org/wiki/Template:Published_case_reports_of_cyproterone_acetate-associated_liver_toxicity -[pic1]: https://imgur.com/a/SAr46aj +[pic1]: https://archive.is/0Te66 @@ -670,7 +703,7 @@ CPA 剂量,不服用,10 mg/天,25 mg/天,50 mg/天,100 mg/天 [M82-GS]: https://scholar.google.com/scholar?cluster=9581511158084858663 [N12-GS]: https://scholar.google.com/scholar?cluster=17139352108227037971 [O18-PDF]: https://researchcommons.waikato.ac.nz/bitstream/handle/10289/12160/Guidelines%20for%20Gender%20Affirming%20Health%20low%20res.pdf -[P70C-GB]: https://books.google.com/books?id=bAihBgAAQBAJ&%3Bpg=PA428 +[P70C-GB]: https://books.google.com/books?id=bAihBgAAQBAJ&pg=PA428 [P70C-WC]: https://worldcat.org/title/419096 [P70C-PDF]: https://files.transfemscience.org/pdfs/Petry%20et%20al.%20%281970%29%20-%20%C3%9Cber%20den%20Einflu%C3%9F%20von%20Cyproteronacetat,%20Norethisteron%C3%B6nanthat%20und%20Gestonoroncapronat%20auf%20die%20Hypophysen-Gonadenachse%20beim%20Mann.pdf [P70B-GS]: https://scholar.google.com/scholar?cluster=16507195795753926943 @@ -680,6 +713,25 @@ CPA 剂量,不服用,10 mg/天,25 mg/天,50 mg/天,100 mg/天 [S87-GS]: https://scholar.google.com/scholar?as_sdt=1%2C5&q=author%3A%22KJ+saborowski%22&hl=en [S87-GB]: https://books.google.com/books?id=9JeKGwAACAAJ [S87-PDF]: https://files.transfemscience.org/pdfs/Saborowski%20(1987)%20-%20Konservative%20Therapie%20mit%20Cyproteronacetat%20und%20Estradiolundecylat%20beim%20Fortgeschrittenen%20Prostatacarcinom_%20Eine%205-Jahres-Studie.pdf -[S87-ENG]: https://docs.google.com/document/d/1s_Z4BXEd3chb4jG6eOSHoSbAwRCynhV3LtKKD_ZI3H8/view +[S87-ENG]: https://files.transfemscience.org/pdfs/translations/Saborowski%20%281987%29%20-%20Konservative%20Therapie%20mit%20Cyproteronacetat%20und%20Estradiolundecylat%20beim%20Fortgeschrittenen%20Prostatacarcinom_%20Eine%205-Jahres-Studie.pdf [S20-PDF]: https://files.transfemscience.org/pdfs/Sofer%20et%20al.%20(2020)%20-%20Differential%20Endocrine%20and%20Metabolic%20Effects%20of%20Testosterone%20Suppressive%20Agents%20in%20Transgender%20Women.pdf [V88-GS]: https://scholar.google.com/scholar?cluster=2098198133343723877 + +[W24]: https://doi.org/10.1080/26895269.2024.2317395 +[A23A]: https://ashm.eventsair.com/QuickEventWebsitePortal/auspath-conference-2023/aus24/Agenda/AgendaItemDetail?id=0c7c2d1d-21c4-4b21-920f-99446f96a548 +[A23A-PDF]: https://az659834.vo.msecnd.net/eventsairaueprod/production-ashm-public/edf3c55f8a984f5390d32e5a2c0093fb +[A23A-THR]: https://www.transresearch.org.au/post/2023_auspath +[A23B]: https://esa-srb-2023.p.asnevents.com.au/days/2023-11-28/abstract/94713 +[A23B-PDF]: https://files.transfemscience.org/pdfs/Angus%20et%20al.%20%282023%29%20-%20The%20effect%20of%20cyproterone%20and%20spironolactone%20on%20breast%20development%20in%20transgender%20women_%20a%20randomised%20controlled%20trial%20%28ESA-SRB-ENSA%202023,%20abstract%20no.%20132%29.pdf +[A23B-EXC]: https://www.endocrinesociety.org.au/All%20abstracts%202023%20ESA&SRB.pdf#page=54 +[A23B-THR]: https://medicine.unimelb.edu.au/mms/mms-staff-news/newsletter-issue-30-december-2023/dr-lachlan-angus-awarded-bryan-hudson-clinical-endocrinology-award +[FVT23]: https://www.endocrine-abstracts.org/ea/0097/ea0097007 +[FVT23-PDF]: https://www.endocrine-abstracts.org/media/031my3zu/bes2023_abstractbook.pdf#page=5 +[GB91-ARC]: https://archive.org/details/sim_urologic-clinics-of-north-america_1991-02_18_1/page/111/ +[G91-ARC]: https://archive.org/details/sim_urologic-clinics-of-north-america_1991-02_18_1/page/83/ +[JTS82-GB]: https://books.google.com/books?id=4HNrAAAAMAAJ +[JTS82-OL]: https://openlibrary.org/works/OL18872483W/Prostate_cancer +[JTS82-WC]: https://worldcat.org/title/7812851 +[JTS82-ARC]: https://archive.org/details/prostatecancer0000unse_l5i2/page/305/ +[K23]: https://doi.org/10.1210/jendso/bvad114.2068 +[Y24]: https://doi.org/10.1080/26895269.2024.2323514