A New Treatment for PCOS? - PCOS Diva
A New Treatment for PCOS?

New Treatment for PCOSIs There a New Treatment for PCOS?

Guest post by Rashmi Kudesia, MD MSc

Reproductive Endocrinologist and Infertility Specialist, RMA of New York

In my experience working with and talking to women with polycystic ovary syndrome (PCOS), one of the most frustrating aspects is the lack of cure. In other words, though there are specific medications that might target irregular or absent ovulation, excess facial or body hair, acne, mood alterations and so on, there doesn’t really exist any one therapy that reliably addresses the constellation of symptoms in this syndrome. As such, there is always much interest when a new drug in the research and development phase holds promise for a broader positive impact in women with PCOS.

Clinical Trials

Just about a year ago, we reported on clinical trials of a drug that was shown in early trials to reduce circulating levels of luteinizing hormone (LH) and testosterone (http://pcosdiva.com/2016/01/new-pcos-treatment-undergoing-clinical-trials/). That drug was in the class of neurokinin 3 (NK3) receptor antagonists (NK3RA). The exciting aspect of that compound was that it seemed to downregulate LH selectively, not shutting down the whole reproductive axis (which would create a pseudo-menopausal state). This action was particularly relevant, because women with PCOS frequently have elevated LH levels, and LH stimulates androgen production.

A Possible New Treatment for PCOS

Though we don’t have much further to say about NK3RA trials, we are now also aware of another drug, Elagolix, which is under study for endometriosis and uterine fibroids. The pharmaceutical company behind this compound, Neurocrine (in collaboration with Abbvie), has also suggested a variety of other women’s health conditions that the drug could benefit, including PCOS. So let’s investigate the potential here.

Elagolix is also an antagonist, meaning it blocks certain enzyme function. In this case, it antagonizes the function of gonadotropin-releasing hormone (GnRH), the hormone released by the hypothalamus in the brain to stimulate the pituitary gland to release not only LH, but also follicle-stimulating hormone (FSH). So, unlike the NK3RA class, which selectively targets LH and its downstream hormones, GnRH antagonism would shut down the entire reproductive axis. This effect is not unlike medications we have on the market currently, such as leuprolide (Lupron), which also results in a shutdown of the reproductive axis.

This type of suppressive approach is particularly beneficial to conditions that worsen in the presence of ovarian estrogen (which is secreted by the growing ovarian follicles in response to FSH). Hence, it makes sense that the initial trials are for endometriosis and fibroids, both conditions that improve with reproductive axis suppression.PCOS Diva supplement features

What impact could it have for women with PCOS?

Well, in general suppressive therapy comes with significant side effects – hot flashes, bone loss, etc. – so some form of “add-back therapy” is used, to add back protective ovarian steroid hormones (estrogen and progesterone) to prevent the unhealthy side effects of premature menopause. In the case of PCOS, it remains to seen what the benefits would be of suppression with add-back over just using a common add-back therapy like birth control pills.

One question I was asked to address was whether there could be healthier or more natural add-back options. In general, professional medical societies have been wary of the purported claims of “bio-identical” or compounded hormonal preparations, and there is not any scientific data to suggest that such hormones are better for most women needing them, and there can be much more variability (and less regulation) in how they are prepared. Regardless, young women with a uterus need both estrogen and progesterone supplementation to keep their heart, bones and uterine linings healthy, so however it is formulated, both hormones would need to be included. I don’t anticipate this approach being of particular assistance to PCOS women.

The second question I was asked was whether this suppression might also help quiet the adrenal production of androgens, particularly DHEAS. As many of you know, androgen hormones are made from both the ovary and the adrenal gland (a little gland that sits on top of the kidneys). Just like the ovary, the adrenal gland is stimulated by the hypothalamus and pituitary and is a parallel hormone axis to the reproductive. Though GnRH antagonism would reduce ovarian androgen production, multiple scientific studies have concluded that it does not suppress the adrenal axis. So for those women suffering from hyperandrogenic symptoms and a high DHEAS level, I do not believe that this approach would be of benefit.

In short, though Elagolix has potential benefit for women’s health, in that it’s an oral suppressive medication (making it potentially better than leuprolide, which is injectable), and may end up working well for women with hormonally-sensitive diseases, shutting down the reproductive axis does not to me seem (even with add-back therapy) a useful step in managing PCOS.

Of the drugs in development now, I would hypothesize that the NK3RA class, which targets the half of the reproductive axis especially overactive in PCOS women, is more likely to help. However, as both of these drugs move through trials, we will be staying tuned for results!

 

Dr. Rashmi Kudesia is a reproductive endocrinologist and infertility specialist who leads RMA of New York’s Brooklyn office. Dr. Kudesia specializes in treating couples who are trying to build their families.
Dr. Kudesia earned her medical degree from Duke University. She completed her residency in obstetrics and gynecology at New York Presbyterian Hospital/Weill Cornell Medical College. She completed her fellowship training in Reproductive Endocrinology and Infertility as well as a Masters of Science in Clinical Research Methods at Albert Einstein College of Medicine.

Dr. Kudesia has received numerous grants and awards for her academic accomplishments and medical research. She was awarded a Global Women’s Health certificate by Mount Sinai School of Medicine in 2011, and was nominated into the Duke Engel Society, which recognizes intellectual development, service and clinical excellence. Dr. Kudesia is the recipient of the Joan F. Giambalvo Scholarship Research Grant from the AMA Foundation in 2013, as well as multiple in-training research grants. Dr. Kudesia served as a Theme Issue Editor for the American Medical Association’s Journal of Ethics’ issue on Innovation in Reproductive Care, and has held multiple regional and national leadership positions within organized medicine.

Dr. Kudesia is an accomplished lecturer and author and has written numerous scientific research articles and manuscripts in leading medical journals. She has presented many of her research findings at national meetings, including the American Society for Reproductive Medicine (ASRM).

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  • 2iceblest

    Every Pharmaceutical drug I have been given for PCOS was a debacle for my body in other ways. How about curing through naturopathic means!

    • Marlene Oddie

      Agree! Loving hormonesbalance.com and thethyroidsecret.com for their informative approach. Everyone is unique, what you feed yourself impacts in a big way!

      • 2iceblest

        I will look into these. Thanks! I’ve been taking multiple supplements for 8 months now that are controlling the PCOS, but I’d like to reverse it if possible. Been dealing with it since my late teens. It came and went until I had my first child, then all h— broke loose and I’ve been struggling for the last 28 years – until last summer!

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