A promising discovery in transgender reproduction

A novel drug regimen helped one transgender woman, who was on long-term hormone replacement therapy then stopped, produce sperm again. 

The results come from a case report published in the Journal of Urology in August 2019. Despite involving only one patient, the findings show an auspicious option for transgender women hoping to have biological children after long-term feminizing hormone use, says to the report’s author. There might be a way to reverse the low fertility going on feminizing hormones causes.  

The case report was led by Joseph Pariser, a urological surgeon who performs gender affirming operations on transgender people at the University of Minnesota Medical School. Pariser counseled a transgender woman who was about to receive a vaginoplasty, a procedure which uses a person’s existing male genitalia to create a vaginal cavity between the urethra and rectum. Before the testicle removal, the patient decided to preserve her sperm in a sperm bank. 

Pariser told the transgender woman to stop her feminizing hormone treatments: estrogen and spironolactone. The woman then began a regimen of 75 units of follitropin alfa, a drug that helps stimulate sperm production, and clomiphene citrate (Clomid), a fertility drug that stimulates ovulation. After six weeks, she recovered her testosterone levels and had motile sperm upon semen analysis. 

“There was no guarantee any of this would work,” Pariser said. “So it’s just one of those things where it’s nice to know all the options.”

Follitropin was perhaps the key to regenerating sperm growth, according to Amanda Adeleye, a reproductive endocrinologist whose work was cited in Pariser’s case report. Follitropin is a follicle stimulating hormone that activates the sertoli cells. The sertoli cells are critical for the development of sperm, said Adeleye.

The follitropin regimen may do more than promote sperm growth in transgender patients thought to be sterile. It could reduce the time the patient must be off feminizing hormones, which induces gender dysphoria in many transgender women. Before this case study, it was thought that a person must be off feminizing hormones for 60 to 70 days for viable sperm to regenerate, Adeleye said. This study showed a period as little as 56 days. 

However, the case report involved only one patient, so clinical trials are needed to determine result reproducibility. Cost is another limiting factor for practical use. The retail price of follitropin alfa is around $2,000 for one vial. Clomid is around $100 for 30 tablets. 

Sixteen states require that insurance companies offer coverage for fertility treatments, though other states, such as Minnesota, ban the coverage of fertility drugs specifically when used to enhance fertility. If an individual’s private insurance does not cover the cost of fertility treatments, patients may have to pay for follitropin and Clomid treatments out of pocket.

The side effects of the treatment are another concern. Follitropin alfa may cause abdominal bloating, diarrhea, nausea and flu-like symptoms in users. Clomid may cause bloating and stomach pain. Of course, these treatments together are not guaranteed to regenerate sperm in transfeminine patients, Pariser says. 

But for patients and professionals alike, this case study reveals an opportunity for reversing low-sperm count after long-term feminizing hormone use in transgender patients. That is much better than accepting the idea of sterilization or harvesting sperm from testicles severed during vaginoplasty operation, says Pariser.

“People’s bodies and people’s testicles are variable, so it’s not a one size fits all,” Pariser said. “You just have to know the options and counsel the patients well.”