Many women with PCOS realize that they have significant hormonal dysfunctions, manifesting in many ways, including menstrual irregularities, thyroid problems, insulin resistance and glucose dysregulation, weight loss resistance, sleep problems, and infertility.
Among the many hormones which can be dysfunctional is progesterone. Of particular concern are an increased risk for miscarriages, pregnancy complications and preterm delivery, irregular cycles, PMS and mood swings, and significantly elevated risk for uterine lining (endometrial) overgrowth (hyperplasia) and uterine cancer!
The elevated uterine (endometrial) cancer risk arises from infrequent and irregular ovulation and from progesterone receptor resistance. The continuous estrogen production characteristic of PCOS results in an imbalanced situation in which there is chronic, unopposed exposure of the uterine lining (endometrium) to estrogen, without the balancing effects of progesterone. The progesterone receptor resistance issue compounds the problem by not allowing the progesterone which is produced to have the desired effects upon progesterone receptors throughout the body. And of course, by not properly impacting the receptors on the uterine lining, the effects of estrogen dominate; increase the cancer risk, with the result being frank endometrial cancer developing, in some cases. Shockingly, such cancers can occur at surprisingly young ages!
Progesterone receptors reside throughout the female body. Among the other progesterone receptors which have received much attention are those in the breasts. In fact, there is now much written that in the event of radiation exposure, both large and small, progesterone can possibly affect certain breast stem cells, now known as cancer stem cells, stimulating them to develop into florid cancer cells.
Of great interest in our evolving understanding of progesterone as a critical regulator has been research into the functioning of the progesterone receptor. As inferred above, several studies in humans have indicated that, in women with PCOS, there is receptor resistance to progesterone in the cell nucleus within those organs which possess progesterone receptors. Progesterone resistance means there is a reduced responsiveness in target tissues to the available progesterone. Gene expression analysis of PCOS endometrium reveals progesterone resistance, but the mechanisms and sensitivity are not yet completely understood.
It is clear, though, that PCOS women with endometrial hyperplasia are more likely than non-PCOS women to proceed further into trouble and have a higher likelihood of developing endometrial carcinoma. There are two forms of the progesterone receptor, A and B, and they are not functionally equivalent. Some animal studies suggest that the A receptor may be key to normal uterine function. Most likely, however, both the A and B forms contribute to the diverse and indispensable actions of progesterone involving cellular events in humans. Progesterone in human females also acts through another set of receptors; these are different from the nuclear receptors. They are membrane-bound progesterone receptors, and these receptors appear to be regulated in normal human endometrium in a cycle-dependent manner, but the precise mechanisms of each membrane progesterone receptor also has yet to be determined.
With the widespread dissemination of information now available, affording a degree of understanding by many women with PCOS that they have significant issues with their progesterone, some have wondered if adding progesterone cream into their PCOS treatment regimen makes sense. Perhaps this could reduce their risk for endometrial (uterine) cancer? Perhaps such hormone use would aid proper sleep, and improve mood and fertility? Perhaps so! There are progesterone products which can be readily purchased over the counter (OTC), without any medical supervision. Does it make sense for a woman with PCOS to buy and use them?
These are excellent questions, and the answer is: maybe “yes” to the use of progesterone as a therapeutic modality, but a resounding “no” to the use of any OTC versions of progesterone.
The biological effects of progesterone depend on the dose, the duration of the stimulus, and the presence, levels, and function of other hormones such as 17 Beta Estradiol, testosterone, thyroid, melatonin, DHEA-S, cortisol, and oxytocin. The woman’s age can also play a role. The application of progesterone as a therapeutic modality is complex and is absolutely not one which should be undertaken without medical supervision. The prescription should be individualized as far as its dose, and absolutely should be formulated by a quality pharmacy. Additionally, the goals involved with its use should be clearly delineated, and the woman using the progesterone must be closely followed and monitored. Depending on the specific needs and situation of the patient, other hormones may be indicated to be prescribed as well.
We live in a world filled with toxins, and some behave as endocrine mimics or so-called endocrine disruptors. Such ubiquitous chemicals play additional havoc with our endocrine systems, creating individualized needs and responses. This adds another layer of complexity which must be considered as therapies are planned. Often a several week detox program prior to the start of progesterone therapy is warranted.
It should always be acknowledged that progesterone is an important and powerful hormone with many effects throughout the body. An over-the-counter product is not able to provide a consistent and therapeutic dose of progesterone, as the actual dosing is truly unknown when such products are utilized and reproducibility does not exist.
I would urge all of you who read this who suffer from PCOS to locate a qualified and caring doctor to work with you, one who will carefully measure your hormone levels and your inflammation markers, and truly look at your total medical picture. If I can personally help any of you on your quest for health, please let me know, as I have created special programs for women who live a distance from my practice in Southern California.
Happily, through lifestyle changes, detoxification, and nutraceutical use, one’s intrinsic hormones can often be improved and this may happily negate the need for prescription hormones. Should that goal not be attainable, it truly is essential that you use only quality, commercially prescribed or compounded progesterone, and not an OTC product, containing unknown ingredients and dosage, and without the critical supervision of a caring and knowledgeable physician.