Review Calls for More Research on Transgender Hormone Therapy

Veronica Hackethal, MD

April 20, 2016

A new review article provides an evidence-based overview of the benefits, risks, and effects of testosterone therapy in transgender men (born female), highlighting the lack of data and need for more research to help guide patient care.

The article was published online April 12 in Lancet Diabetes & Endocrinology.

"A major limitation in the study of transgender medicine is a paucity of high-quality data. Difficulties in obtaining such data stem from the scarcity of randomized controlled trials (partly because of ethical issues), few prospective and long-term studies, the use of suboptimum control groups, loss to follow-up, and difficulties in recruitment of representative samples, including people disenfranchised from society and medical care," writes Michael S Irwig, MD, associate professor of medicine at the George Washington University School of Medicine and Health Sciences and director of the Andrology Center at the George Washington Medical Faculty Associates.

Dr Irwig recently published another study that found that many transgender individuals need better access to healthcare and that providers also need more training in transgender care.

The new review includes articles about testosterone therapy in transgender men published in English and Spanish mainly over the past 15 years, between January 2000 and April 2016. Older articles deemed very important were also included. The paper also provides some comparisons with testosterone therapy in women and hypogonadal men. It does not cover the care of transgender adolescents, however.

Testosterone: Weighing Pros and Cons

On the whole, the review found testosterone therapy to be safe in the short term, though long-term effects are relatively unknown.

The article provides a table of the main types of testosterone formulations available around the world, along with doses, advantages, and disadvantages of each. No standards exist for starting or maintenance doses of testosterone in transgender men.

In general, the effects of testosterone therapy become apparent within a few months of starting treatment and vary by formulation.

Desirable effects include increased growth of facial and body hair, more lean muscle mass and strength, drop in fat mass, lowering of the voice, increased libido, disappearance of menstruation, growth of the clitoris (sometimes accompanied by pain), and improved well-being related to reductions in gender dysphoria, stress, anxiety, and depression. Some studies also suggest improvements in cognition, but the topic remains understudied.

Testosterone therapy can also cause changes in breast composition and is linked to reduced risk for breast cancer, whether or not the individual has undergone mastectomy. So far no evidence exists to guide decision making about the appropriate interval for mammography screening, Dr Irwig points out.

The most common drawback of testosterone therapy is acne, which can be treated with topical or oral medication. Other less desirable effects include changes to the vagina, endometrium, and ovaries (the last can take on characteristics of polycystic ovarian syndrome), hair loss, and increased hemoglobin and hematocrit.

Testosterone therapy might also increase the risk of type 2 diabetes and metabolic syndrome, although research is inconsistent.

In 2014, the US Food and Drug Administration required manufacturers to place a general warning about the risk for blood clots on testosterone products. The review found that research does not seem to support a link between testosterone therapy and blood clots in transgender men, but studies may have not have been large enough to evaluate this issue.

Testosterone therapy is also linked to decreased HDL cholesterol and increased triglycerides and potentially increases blood pressure, the long-term effects of which remain unknown. The role of testosterone therapy in risk for cardiovascular events is controversial and poorly understood, according to the review.

No prospective studies have looked at mortality rates in transgender men on testosterone therapy, and comparison studies for transgender men vs the general population show conflicting results.

"Since transgender medicine is a fairly new field, more research is needed, especially in the form of larger and longer prospective studies that include diverse populations," Dr Irwig concludes.

Dr Irwig reports no relevant financial relationships.

Lancet Diabetes Endocrinol. Published online April 12, 2016. Abstract

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