Effect of 100 mg of testosterone cypionate in trans men with erythrocytosis: a randomized controlled pilot study.

Abstract

Background: Testosterone cypionate is commonly administered at 200 mg every 2 weeks to facilitate masculinization in transgender men. However, this regimen may increase hematocrit (Hct) by up to 6.9%.

Aim: To compare the effects of biweekly intramuscular administration of 100 mg testosterone cypionate versus testosterone suspension on hematologic parameters and testosterone concentration in transgender men with erythrocytosis.

Methods: A randomized, controlled pilot clinical trial which enrolled transgender men aged 18-40 years with secondary erythrocytosis (Hct ≥ 50%) related to testosterone therapy. Exclusion criteria included current contraceptive use, severe psychiatric disorders, or Hct ≥ 55%. Participants received either biweekly supervised intramuscular injections of 100 mg testosterone cypionate for 3 months or underwent complete testosterone withdrawal.

Main outcome measures: Hct, hemoglobin, and total testosterone concentrations.

Results: Forty-three participants completed the study protocol. Greater reductions in Hct were observed in the control group (-3.5 ± 0.5% vs -0.8 ± 0.5%; P < .001), as well as in hemoglobin (-0.97 ± 0.16 g/dL vs -0.17 ± 0.17 g/dL; P = .002) and testosterone (-510.16 ± 120.42 ng/dL vs 75.72 ± 123.26 ng/dL; P = .002). However, this difference was significant only when a >1.0 percentage point reduction in Hct was expected. In the intervention group, reductions in diastolic blood pressure (117.05 ± 13.72 mmHg vs 113.19 ± 12.77 mmHg; P = .040), body weight (70.59 ± 15.16 kg vs 69.34 ± 14.44 kg; P = .003), and HADS anxiety scores (7.90 ± 4.37 vs 5.19 ± 4.17; P = 0.001) were also observed. No serious adverse events were reported.

Clinical implications: Dose reduction, although less effective than complete testosterone suspension in lowering Hct, suggests a potentially valuable strategy for patients with moderately elevated Hct levels. In this group, Hct levels remained stable and within acceptable limits, while therapeutic serum testosterone concentrations were preserved.

Strengths and limitations: To our knowledge, this is the first clinical trial to assess the impact of testosterone dose fractionation in transgender men, with close monitoring and follow-up in both intervention arms. Among the study's limitations are the absence of a sham control group and the use of a convenience sample recruited from a single specialized center.

Conclusion: Testosterone suspension appears to be more effective in reducing Hct than dose reduction when a decrease greater than 1% in Hct is desired. Nonetheless, dose reduction preserved therapeutic testosterone levels while offering additional benefits in blood pressure, anxiety, and body weight.