Feminising Hormone Therapy Alters Blood Proteins in Transgender Women

Key Takeaways:

• Feminising hormone therapy changes thousands of blood proteins toward cisgender female patterns
• Study reveals potential long-term health implications including autoimmune and asthma risks
• Researchers call for more inclusive medical research for transgender healthcare

A groundbreaking study published in Nature Medicine reveals that feminising gender-affirming hormone therapy (GAHT) fundamentally alters protein profiles in transgender women’s blood, creating biological patterns more aligned with cisgender women.

University of Melbourne endocrinologist Dr. Ada Cheung, who co-led the research, described the findings as “a world-first” in understanding the comprehensive biological effects of hormone therapy.

How Hormone Therapy Reshapes Biology

Feminising GAHT typically combines estrogen with antiandrogens like cyproterone acetate (CPA) or spironolactone. While doctors have known since the 1970s that these treatments redistribute fat, reduce body hair, and develop breast tissue, the new research shows changes extend much deeper.

The study followed 40 transgender women in Melbourne, with half receiving estrogen+CPA and half estrogen+spironolactone. Researchers analyzed over 5,000 proteins in blood samples collected before and after six months of treatment.

Results showed 245 proteins changed significantly with CPA and 91 with spironolactone. Most protein levels decreased, with changes attributed to three key factors: reduced testosterone, increased body fat percentage, and higher breast volume.

Protein Patterns Shift Toward Female Profiles

Comparing results with the UK Biobank’s protein database, researchers found GAHT shifted 36 proteins associated with CPA and 22 with spironolactone toward patterns typically seen in cisgender women.

“The changes go far beyond what we see on the outside; they happen deep inside the body’s cells and systems,” Dr. Cheung explained.

Potential Health Implications

The study identified possible long-term health considerations:

• Both treatment types showed protein patterns suggesting increased asthma and autoimmune disease risks
• Only CPA use indicated potentially lower atherosclerosis risk
• Experts emphasize these are theoretical risks not yet observed clinically

Dr. Cheung cautioned that these are “only possibilities, not proven. We don’t yet have clinical evidence showing higher rates of these diseases in trans women on hormones.”

Dr. Sanjay Kalra, former president of the Indian Professional Association for Transgender Health, confirmed he hasn’t observed increased autoimmune susceptibility in his clinical practice.

Future Research Directions

The research team is now extending their work to masculinising GAHT. Dr. Kalra hopes the study will inspire similar research in India, where transgender healthcare access remains inconsistent.

The study’s most significant contribution, according to Dr. Cheung, is highlighting “the need for high-quality, inclusive science so that trans people can receive the best possible care based on real data.”