Related Experiment Video
Updated: Nov 20, 2025
Establishment of Rat Models Mimicking Gender-affirming Hormone Therapies
Published on: January 10, 2025
Differential Endocrine and Metabolic Effects of Testosterone Suppressive Agents in Transgender Women
Yael Sofer1, Iris Yaish2, Marianna Yaron2
1From the Institute of Endocrinology, Diabetes, Metabolism and Hypertension, Tel Aviv-Sourasky Medical Center, Tel Aviv, Israel; the Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Objective:
Suppression of testosterone secretion and/or action in transgender women using cyproterone acetate (CPA), spironolactone, or gonadotropin-releasing hormone analogues (GA) is achieved through various mechanisms. Our objective was to characterize possible differential effects of these compounds on metabolic and endocrine variables.
Methods:
We conducted a historic cohort study of transgender patients treated in a tertiary referral center. A longitudinal analysis of treatment naïve patients and a cross-sectional analysis of the whole cohort at the last visit was carried out.
Results:
Among 126 transgender women (75 treatment-naïve), CPA was the predominant androgen suppressive therapy (70%), followed by spironolactone (17.6%), and GA (10.2%). Among those who were treatment-naïve, the increase in serum prolactin levels over baseline was greater at 3 months following CPA initiation (mean change 397 ± 335 mIU/L) than following spironolactone (20.1 ± 87 mIU/L) or GA initiation (64.6 ± 268 mIU/L; P = .0002). Prolactin levels remained higher in the CPA-treated group throughout follow-up, irrespective of estradiol levels, which were similar between the groups. A worse metabolic profile was associated with treatment with CPA than with spironolactone or GA. In the CPA compared to the spironolactone and GA groups, high-density lipoprotein-cholesterol levels were lower (47.1 ± 10.4, 54.4 ± 12.2, and 60.3 ± 13, respectively; P = .0076), while body mass index levels (24.3 ± 5, 21.7 ± 2.3, and 20.7±3.1 kg/m2; P = .03), and systolic (117 ± 12.1, 109 ± 12.2, and 105 ± 13.3mm Hg; P = .01) and diastolic (74 ± 9, 65.6 ± 5.5, and 65.4 ± 11 mm Hg; P = .0008) blood pressure levels were higher at the last visit.
Conclusion:
Treatment of transgender women with CPA was associated with hyperprolactinemia and a worse cardiovascular risk profile than treatment with spironolactone or GA.
Abbreviations:
BMI = body mass index; CPA = cyproterone acetate; E2 = estradiol; FSH = follicle-stimulating hormone; GA = gonadotropin-releasing hormone analogues; LH = luteinizing hormone.
Insights
Cyproterone acetate (CPA) treatment in transgender women is linked to higher prolactin levels and a worse cardiovascular risk profile compared to spironolactone or gonadotropin-releasing hormone analogues (GA). These findings highlight potential differential effects of androgen suppressive therapies.
Area of Science:
- Endocrinology
- Metabolic Health
- Transgender Healthcare
Background:
- Transgender women often use androgen suppressive therapies like cyproterone acetate (CPA), spironolactone, or gonadotropin-releasing hormone analogues (GA) to suppress testosterone.
- These therapies work through various mechanisms, but their differential effects on metabolic and endocrine variables are not fully characterized.
- Understanding these differences is crucial for optimizing hormone therapy and minimizing health risks in transgender women.
Purpose of the Study:
- To compare the effects of cyproterone acetate (CPA), spironolactone, and gonadotropin-releasing hormone analogues (GA) on metabolic and endocrine variables in transgender women.
- To investigate potential differential impacts on serum prolactin, lipid profiles, body mass index (BMI), and blood pressure.
Main Methods:
- Historic cohort study of transgender patients treated at a tertiary referral center.
- Longitudinal analysis of treatment-naïve patients and cross-sectional analysis of the entire cohort.
- Comparison of endocrine and metabolic parameters across different androgen-suppressive treatments.
Main Results:
- Cyproterone acetate (CPA) was the most common therapy (70%), followed by spironolactone (17.6%) and GA (10.2%).
- CPA treatment was associated with significantly greater increases in serum prolactin levels compared to spironolactone or GA.
- CPA users exhibited a worse metabolic profile, including lower HDL-cholesterol and higher BMI, systolic, and diastolic blood pressure compared to spironolactone or GA users.
Conclusions:
- Treatment with cyproterone acetate (CPA) in transgender women is linked to hyperprolactinemia.
- CPA is associated with a less favorable cardiovascular risk profile compared to spironolactone or gonadotropin-releasing hormone analogues (GA).
- These findings suggest important differential effects of these androgen-suppressive agents on metabolic and endocrine health.
Related Concept Videos
01:26Testosterone: Functions and Regulation
01:27Major Hormones and Their Functions
Oxytocin, produced in the hypothalamus and released by the pituitary gland, plays a role in social bonding, childbirth, and...
01:27Signs of Puberty
01:19Factors Affecting Drug Biotransformation: Biological
Species differences: Variations in enzyme systems across species can cause disparities in drug metabolism. For instance, humans may metabolize certain drugs faster than rodents, altering therapeutic effects.
Strain differences: Genetic variations within a species can result in differing enzyme activity, impacting drug response and toxicity. For example, some mouse strains may...
01:29Therapeutic Drug Monitoring: Affecting Factors
01:22Target Cell Response to Hormones
Notably, the cellular response can be regulated by altering the number of receptors expressed in the cell. For example, prolonged exposure to elevated hormone levels results in a gradual decline or down-regulation in the number of receptors for that specific hormone on the cell surface. Conversely, in response to low hormone levels, cells may use up-regulation, producing an...