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Male hormones and female fertility

Dr. Sajana Rajan

Several fertility clinics across the country are beginning to administer testosterone, either through a patch or a gel on the skin, to increase the number of eggs produced by certain women undergoing In vitro fertilization (IVF). Women are also purchasing over-the-counter supplement DHEA, which is converted by the body into testosterone, to boost their chances of pregnancy with IVF.

A new study shows that male hormones play an important role in female fertility and might enhance the possibilities of IVF therapy. A few clinical trials support the use of testosterone given through the skin, while others have shown no benefit of DHEA – also used in attempts to slow aging and enhance muscle mass – in increasing pregnancy and birth rates in women who don’t respond well to IVF therapy. Lacking a large and convincing body of data on the topic, the jury is still not fully convinced whether male hormones such as testosterone improves female fertility.

Male hormones, also called androgens, help drive the development of follicles – structures that contain and ultimately release an egg that can be fertilized by a man’s sperm. Published in the Proceedings of the National Academy of Sciences, the research also details how male hormones boost the production of follicles in mice. Authors believe the study provides potential biological targets to enhance fertility in women with diminished ovarian reserve, who produce few or no follicles in response to IVF drugs designed to boost follicle development.

Effect of male hormones on female fertility

There is a raging debate in the reproductive endocrinology field about what male hormones are doing in female fertility. Our study doesn’t solve the controversy, but, along with some earlier seminal studies from other groups, it does tell us that we can’t dismiss male hormones. They might actually be doing something useful. Androgens are increasing follicle growth and ensuring follicles don’t die – exactly what you want when providing fertility treatment.

The study was conducted on female mice and found that androgens, particularly testosterone, are necessary for normal ovarian function. The androgens seem to promote the growth of the follicles responsible for containing and then releasing mature eggs. Male hormones also prevent the follicles from dying at an earlier age. Therefore, women with lower-levels of androgens, and perhaps those who have reduced numbers of androgen receptors, may suffer from fewer follicles altogether as well as follicles that die before the egg has a chance to mature and be released. Owing to these reasons, testosterone treatments may become a part of IVF treatment.

Is it clinically proven..?

It is still a mystery as to the exact roles testosterone and other androgens play on female fertility, because the body of evidence is still small. However these recent findings will inspire endocrinologists to dig deeper into the mystery. DHEA (dehydroepiandrosterone) supplements – rumored to slow down the gaining process, improve memory and energy levels, and boost the immune system – are now being recommended for women who haven’t responded well to IVF treatments . While a few clinical trials have shown DHEA to improve IVF success rates, bona fide medical studies have yet to correlate any connection between DHEA supplementation and improved transfer and live birth rates.

However, the recent research from the University of Rochester School of Medicine and Dentistry, does seem to indicate that testosterone may be part of the solution for certain women struggling with fertility issues. As a result, some IVF clinics have begun adding testosterone therapy to women who meet certain conditions, via a skin patch or gel applied to and absorbed by the skin, in an effort to increase the number of eggs produced for their IVF cycles. Women most likely to benefit from testosterone therapy are those who are identified as having diminished ovarian reserves as well as women in their 40s who are trying to get pregnant

Using multiple animal models and cell experiments, some researchers at the University of Rochester Medical School found that male hormones promote follicle development in two ways. First, they prevent follicles from dying at an early stage. They do this by ramping up a molecule that stops cells from self destructing, a process called apoptosis. The researchers, Hammes and Sen speculate that if a woman doesn’t have enough androgens (male hormones), more of her follicles may be dying and fewer progressing to a mature stage when they produce and release an egg.

Secondly, androgens make ovarian cells more sensitive to follicle-stimulating hormone or FSH, which promotes follicle growth. They do this by creating more FSH receptors – molecules on the surface of ovarian cells that jumpstart the follicle making process in response to the hormone.

“Androgens are increasing follicle growth and ensuring follicles don’t die – exactly what you want when providing fertility treatment,” noted Hammes, who is also the chief of the Division of Endocrinology and Metabolism at UR Medicine’s Strong Memorial Hospital.

When the team administered small doses of androgens to mice that were taking the equivalent of medications given to women undergoing IVF therapy, they developed more mature, egg-containing follicles than mice that didn’t receive androgens. The androgen-treated female mice also released larger numbers of eggs with ovulation. IVF drugs are designed to do just that, enhance ovulation – the production and discharge of an egg or eggs from the ovary. Unfortunately, these drugs aren’t always effective in women with diminished ovarian reserve.

Women above 40 produce less follicles

Kathleen M. Hoeger, M.D., M.P.H., director of UR Medicine’s Strong Fertility Center, estimates that around 20 percent of the patients her team treats have diminished ovarian reserve, meaning they produce fewer follicles than estimated based on their age. Women who are 40 years or older are most likely to have diminished ovarian reserve, but it can appear in younger women as well.

“This information is important because it provides theoretical support for administering androgens to some women undergoing IVF, a practice that our fertility clinic and many others across the country have started in recent years,” said Hoeger, who is also a professor of Obstetrics and Gynecology at the School of Medicine and Dentistry. “If these data are confirmed in clinical trials, we could propose that raising low levels of androgens in a woman with diminished ovarian reserve might increase her ability to produce more and better eggs for fertilization.”

Hammes says the study calls for further clinical trials to determine whether androgens can have a positive effect on fertility when given at the right doses. And, by better understanding the biological pathways that are important for follicle development, scientists may be able to target these pathways with drugs or other interventions to improve IVF success rates.