Testosterone and Ovarian Stimulation in Transmasculine Patients

Abstract and Introduction

Abstract

Approximately 50% of transmasculine people use testosterone for gender affirmation, yet very little is known about the effects of testosterone on future reproductive capacity. Moreover, there are no data to guide fertility specialists on how to manage testosterone leading up to or during ovarian stimulation. Most clinics require cessation of testosterone prior to ovarian stimulation in this setting of no data; however, the current literature does suggest a potential increase in dysphoria with cessation of testosterone and during stimulation. This divergence begs the question of whether clinicians may be doing more harm than good by enacting this requirement. Here, we present two cases of transmasculine individuals who were on testosterone prior to stimulation and maintained their testosterone dosage throughout stimulation as proof of concept, followed by a discussion of current clinical practice and providing some rationale to support continuation of testosterone throughout stimulation.

Introduction

In the USA, ~1.5 million adults, or 0.7% of the population, identify as transgender individuals (people whose gender identity differs from their sex assigned at birth) (Jones, 2022). These numbers can be expected to grow as many studies of youth cite higher proportions of individuals with transgender and non-binary (TGNB) identities, experiences, and expression (1–30%) (Wilson et al., 2017), and recent data note that 1 in 48 Generation Z adults are transgender (Jones, 2022). Further, increasing visibility and socio-political acceptance make disclosure of TGNB identities more common.

Gender affirmation processes (or 'transition') include many actions that help bring one's gender expression (outward appearance) and physiological processes (e.g. hair growth, voice changes, fat distribution, menstrual patterns) into alignment with one's affirmed gender identity. For transmasculine people (individuals who identify as men or on the masculine spectrum and were assigned female sex at birth), these actions include social elements of transition (e.g. changing name, pronouns, driver's license, insurance paperwork, hair, clothes, makeup), medical transition (e.g. using testosterone for masculinization, menstrual suppression), and surgical transition (e.g. chest reconstruction or masculinization—mastectomy, hysterectomy, bilateral salpingo-ophorectomy, vaginectomy, metoidioplasty, scrotoplasty, phalloplasty). As of 2015, in the USA, while 49% of TGNB people assigned female at birth employ testosterone for gender affirmation, far fewer (8% overall) have had a hysterectomy with or without oophorectomy (James et al., 2016). Considering demographic changes, increasing visibility and disclosure, and access to gender-affirming hormones, the number of people of reproductive age on gender-affirming hormones is expected to grow.

Contrary to popular belief, many TGNB people desire to have genetically related children or regret not having that opportunity, and some transmasculine individuals desire to or have carried a pregnancy themselves, even after gender affirmation processes have been initiated (Wierckx et al., 2012; Light et al., 2014; Armuand et al., 2017; Tornello and Bos, 2017; Auer et al., 2018; Chen et al., 2018; Moseson et al., 2021; Vyas et al., 2021). Both national and international organizations have put forth guidelines recommending fertility preservation counseling prior to gender-affirming treatments, including hormone therapy (Ethics Committee of the American Society for Reproductive Medicine, 2015; Hembree et al., 2017; Coleman et al., 2022). Nonetheless, utilization of fertility preservation services remains low among the TGNB population, particularly transmasculine people (Chen et al., 2017; Nahata et al., 2017; Auer et al., 2018; Riggs and Bartholomaeus, 2018). As such, fertility providers will need to grapple with IVF protocols for a subset of transmasculine patients who have already initiated testosterone and are now presenting for fertility treatment in the absence of data-driven practice guidelines. There are published and anecdotal reports of clinics requiring 1–6 months' testosterone cessation prior to IVF, with many clinics requiring the use of oral contraceptive pills or return of menses prior to ovarian stimulation for IVF (De Roo et al., 2016; Armuand et al., 2017; Neblett and Hipp, 2019). Unfortunately, cessation of testosterone often causes 'female-range' serum estradiol levels and return of menses, which can be distressing to transmasculine individuals and increase gender dysphoria (Mitu, 2016; Armuand et al., 2017). Moreover, there is currently no compelling evidence in support of discontinuing testosterone for ovarian stimulation, which begs the question if we could be creating unindicated, unnecessary distress in this patient population by enacting such a requirement. Here, we present two cases of transmasculine individuals who underwent IVF at a single fertility center while continuing gender-affirming testosterone therapy throughout stimulation as a proof of principle, then discuss contemporary practice questions.