MON-193 - Vasomotor Symptoms on Gender-Affirming Testosterone Therapy

Case Presentation—A 26-year-old transmasculine patient on testosterone therapy presented with persistent and debilitating vasomotor symptoms. They started testosterone and underwent bilateral mastectomy at age 18, and subsequently had a hysterectomy and bilateral oophorectomy at age 21. Their regimen consisted of topical testosterone 30 mg daily. Laboratory studies revealed total testosterone 332 ng/dL (300–1080 ng/dL), estradiol < 12 pg/mL ( < 41 pg/mL), SHBG 22 nmol/L (17–56 nmol/L), FSH 80.8 mIU/mL (1.6–9 mIU/mL), LH 51.5 mIU/mL (2–12 mIU/mL), TSH 0.39 µIU/mL (0.3–4.7 µIU/mL), and free T4 1.7 ng/dL (0.8–1.7 ng/dL).

The persistent vasomotor symptoms were suspected to be related to undetectable estradiol levels. After a discussion of potential therapeutic options, a low-dose estradiol patch (0.0375 mg/day) was started with the goal of raising estradiol levels into the cis-male range. The patient subsequently reported resolution of vasomotor symptoms. Repeat laboratory studies showed total testosterone 612 ng/dL, estradiol 36 pg/mL, SHBG 22 nmol/L, FSH 22.8 mIU/mL, and LH 15.4 mIU/mL. At follow-up 18 months later, the patient’s laboratory studies remained stable and they denied recurrence of symptoms.

Discussion— In our experience, vasomotor symptoms are not a common finding in post-oophorectomy transmasculine patients receiving testosterone. Testosterone suppresses gonadotropins and thereby reduces estradiol levels. Studies of patients receiving testosterone therapy after oophorectomy have shown an additional decrease in estradiol levels post-operatively that is associated with a corresponding increase in gonadotropins. This suggests that peripheral aromatase activity alone may not be sufficient to maintain estradiol levels in some patients. One potential explanation for the marked vasomotor symptoms in our patient could be previously described CYP19A1 polymorphisms associated with reduced aromatase activity.

Given the positive impact of estradiol on bone health, the physiologic impact of low estradiol could extend beyond development of vasomotor symptoms. Several studies have demonstrated that oophorectomy in transmasculine patients can be associated with reductions in bone density despite receiving testosterone replacement therapy. As such, it is prudent to assess estradiol in patients on testosterone with pronounced vasomotor symptoms after oophorectomy. Estradiol replacement can provide symptomatic relief and additional studies can clarify whether it is also beneficial for long-term bone health.

Conclusion—Although vasomotor symptoms are uncommon in post-oophorectomy transmasculine patients on testosterone, symptoms occurring in the setting of low estradiol levels can be effectively treated with low-dose estradiol therapy to maintain levels in the cis-male range.

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