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.
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