Department of Obstetrics and Gynecology, University of Washington, Seattle, WA.
The Permanente Medical Group; Seattle, WA.
Am J Obstet Gynecol. 2020 Aug;223(2):229.e1-229.e8. doi: 10.1016/j.ajog.2020.01.059. Epub 2020 Feb 8.
An estimated 1.4 million persons in the United States identify as transgender or nonbinary, signifying that their gender identity does not correspond with their assigned sex at birth. Individuals assigned female at birth may seek gender-affirming hormone therapy with testosterone. No studies have directly examined ovulatory function in transmasculine individuals using injectable testosterone.
Our primary objective was to determine the effect of testosterone on ovulatory suppression in transmasculine individuals. Secondary objectives were to determine predictors of ovulation in transmasculine individuals on testosterone, and to assess the effect of testosterone on antimüllerian hormone.
This prospective observational study recruited participants from a community clinic that provides gender-affirming hormone therapy. Enrolled individuals were assigned female at birth and were currently using or seeking to initiate masculinizing therapy with injectable testosterone esters (transmasculine individuals). Over a 12-week study period, participants collected daily urine samples for pregnanediol-3-glucoronide testing and completed daily electronic bleeding diaries. We assessed monthly serum mid-dosing interval testosterone, estradiol and sex hormone binding globulin, and antimüllerian hormone values at baseline and study end. Ovulation was defined as pregnanediol-3-glucoronide greater than 5 μg/mL for 3 consecutive days. The primary outcome was the proportion of participants who ovulated during the study period. We examined predictors of ovulation such as age, length of time on testosterone, serum testosterone levels, body mass index, and bleeding pattern.
From July to November 2018, we enrolled 32 individuals; 20 completed the study (14 continuing testosterone users, 6 new users). Median age was 23 years (range 18-37 years). Bleeding or spotting during the study period was noted by 41% of participants (13/32). Among continuing users, median testosterone therapy duration was 11 months (range 1-60 months). A single ovulation was observed out of a total of 61 combined months of testosterone use; however, several transient rises in pregnanediol-3-glucoronide followed by bleeding episodes were suggestive of 7 dysfunctional ovulatory cycles among 7 individuals. There was no difference in antimüllerian hormone from baseline to 12 weeks between participants initiating testosterone and continuing users of testosterone. We did not have the power to examine our intended predictors given the low numbers of ovulatory events, but found that longer time on testosterone and presence of vaginal bleeding over 12 weeks were associated with transient rises in pregnanediol-3-glucoronide.
This study suggests that testosterone rapidly induces hypothalamic-pituitary-gonadal suppression, resulting in anovulation in a proportion of new users. Importantly, these data also suggest that some long-term testosterone users break through the hormonal suppression and experience an ovulatory event, thereby raising concerns pertaining to the need for contraception in transmasculine individuals engaged in sexual intercourse with sperm-producing partners. Given the small number of overall participants, this work is hypothesis generating. Larger studies are needed to confirm and to clarify these findings.
据估计，美国有 140 万人自认为是跨性别者或非二元性别者，这表明他们的性别认同与出生时分配的性别不符。出生时被指定为女性的人可能会寻求使用睾丸素来进行性别肯定激素治疗。目前尚无研究直接检查使用注射用睾酮的跨性别男性的排卵功能。
我们的主要目的是确定睾丸素对跨性别男性排卵抑制的影响。次要目标是确定接受睾丸素治疗的跨性别男性排卵的预测因素，并评估睾丸素对 AMH 的影响。
这项前瞻性观察性研究招募了来自提供性别肯定激素治疗的社区诊所的参与者。入组的参与者出生时被指定为女性，目前正在使用或寻求开始使用注射用睾酮酯进行男性化治疗（跨性别男性）。在为期 12 周的研究期间，参与者每天采集尿液样本进行 pregnanediol-3-glucoronide 检测，并完成每日电子出血日记。我们在基线和研究结束时评估每月的血清中剂量间隔睾酮、雌二醇和性激素结合球蛋白以及 AMH 值。排卵定义为连续 3 天 pregnanediol-3-glucoronide 大于 5 μg/mL。主要结局是研究期间发生排卵的参与者比例。我们检查了排卵的预测因素，如年龄、使用睾丸素的时间长短、血清睾酮水平、体重指数和出血模式。
2018 年 7 月至 11 月期间，我们招募了 32 名参与者；20 名完成了研究（14 名继续使用睾丸素，6 名新使用者）。中位年龄为 23 岁（18-37 岁）。41%的参与者（32 名中的 13 名）在研究期间出现出血或点滴出血。在继续使用睾丸素的参与者中，睾丸素治疗的中位持续时间为 11 个月（1-60 个月）。在总共 61 个月的睾丸素使用中观察到单次排卵；然而，在 7 名参与者中，有 7 人出现了孕激素-3-葡糖苷酸短暂升高后伴出血事件，提示 7 个排卵功能障碍周期。在开始使用睾丸素的参与者和继续使用睾丸素的参与者中，从基线到 12 周时 AMH 没有差异。由于排卵事件数量较少，我们没有能力检查我们预期的预测因素，但发现使用睾丸素的时间较长和 12 周内出现阴道出血与孕激素-3-葡糖苷酸的短暂升高有关。
本研究表明，睾丸素迅速诱导下丘脑-垂体-性腺轴抑制，导致一部分新使用者无排卵。重要的是，这些数据还表明，一些长期使用睾丸素的人会突破激素抑制，出现排卵事件，这引发了关于与精子产生伴侣发生性行为的跨性别男性需要避孕的问题。鉴于参与者总数较少，这项工作只是提出了假设。需要更大规模的研究来证实和阐明这些发现。
