Progesterone has anti-androgen benefits and can promote ovulation. Which makes progesterone therapeutic for polycystic ovary syndrome, as described in my recent paper The central role of ovulatory disturbances in the etiology of androgenic polycystic ovary syndrome (PCOS)—Evidence for treatment with cyclic progesterone.
By “progesterone,” I mean real progesterone, also called body-identical progesterone or oral micronized progesterone (OMP), available as products like Prometrium, Utrogestan, Teva, and Famenita, depending on your country . Progestins, on the other hand, are not progesterone and do not provide the same ovulation-promoting effect. And while some progestins (eg drospirenone) are anti-androgenic, others (eg levonorgestrel) are androgenic or testosterone-like and can worsen the androgen excess and insulin resistance of PCOS.
PCOS starts in the brain
Much of the evidence points to a “neuroendocrine” basis for PCOS, which means that dysfunction in the brain, or more specifically, in the hypothalamus, is the primary cause of ovarian androgen excess. It works like this:
In a normal, healthy menstrual cycle, the hypothalamus releases pulses of GnRH (gonadotrophin-releasing hormone), first slowly, then more rapidly, and then slowly again after ovulation. In turn, those pulses stimulate the pituitary hormones (FSH and LH) that coordinate ovulation and promote healthy production of estrogen and progesterone.
A key feature of a healthy neuroendocrine system is the beneficial effect of progesterone slowing the pulsatility of GnRH. In other words, progesterone (produced by ovulation) causes a beneficial negative feedback in the hypothalamus, thereby reducing androgens and promoting future ovulation.
In PCOS, rapid GnRH pulses result in chronic LH surges, androgen excess, insulin resistance, and ultimately, progesterone deficiency due to anovulation.
Unfortunately, the lack of progesterone promotes a vicious cycle of impaired feedback to the hypothalamus, leading to continued rapid GnRH pulses and further anovulation.
👉🏽 Tip: High GnRH pulsatility is caused by a combination of genetics and epigenetics resulting from in-utero exposure to androgens and environmental toxins. High insulin or insulin resistance also contributes to high GnRH pulsatility.
Cyclic progesterone therapy to lower androgens
According to Professor Jerilynn Prior, “Cyclic progesterone therapy is treatment using the natural progesterone hormone (oral micronized progesterone, Prometrium® or compounded in oil) in a way that mimics the normal pattern (14 days in the last half of the menstrual cycle) and amount (300 mg at bedtime).”
In our paperProfessor Prior and I explain four mechanisms by which cyclic progesterone therapy may improve androgenic PCOS:
- By inducing withdrawal bleeds, progesterone can prevent endometrial hyperplasia, atypia, and endometrial cancer. Tip: If cyclic progesterone doesn’t cause withdrawal bleeds, it’s probably not PCOS.
- By competing for the enzyme 5-alpha-reductase, progesterone reduces dihydrotestosterone (DHT), the active form of testosterone, thus relieving acne, hirsutism, and androgenic alopecia. This is the same enzyme that converts progesterone to the calming neurosteroid allopregnanolone, which is why progesterone is often good for mood.
- By increasing the metabolic rate, progesterone can promote weight loss.
And above all:
- Cyclic progesterone “addresses the central pathophysiology of androgenic PCOS by slowing the pulse frequency of both GnRH and LH to allow normal FSH and follicle growth and to promote normal reproductive cyclicity, ovulatory menstrual cycles, and fertility .”
By slowing GnRH pulsatility and lowering androgens, cyclic progesterone therapy can also help improve insulin resistance.
How to take cyclic progesterone therapy
Many of my PCOS patients have had success with cyclic progesterone at a lower dose of 100 mg at bedtime. Takes the cycle two weeks in, two weeks vacation.
👉🏽 Tip: It is best to take progesterone at bedtime because oral progesterone can be very sedating. Taking it during the day can cause grogginess and depression.
If cycles are irregular and anovulatory, the starting dose is two weeks on and two weeks off until regular ovulation is established.
When cycles become ovulatory, switch to taking progesterone in just two weeks of the luteal phase (ie, starting a day or two after ovulation). After six or more ovulatory cycles, you can stop taking progesterone as you are now taking it.
To get oral micronised progesterone, you will need a prescription from your doctor. You can try saying:
“Can I try a few months of Prometrium for PCOS? According to this Canadian endocrinology professor, progesterone can cause withdrawal bleeds and improve androgen symptoms.
Show your doctor a printed copy of our paper The central role of ovulatory disturbances in the etiology of androgenic polycystic ovary syndrome (PCOS)—Evidence for treatment with cyclic progesterone and say “you want to try it for three months.” If your doctor is hesitant, offer to leave it to him and come back for a second appointment. Email me for a PDF copy of the full paper.
Is progesterone safe?
Unlike progestins, which are associated with mood effects and an increased risk of breast cancer, progesterone is safe for the body. For example, progesterone is generally beneficial for mood and sleepand according to Professor Prior, Natural progesterone may even help reduce the risk of breast cancer.
As discussed in my blog post “Guide to progesterone,” cyclic progesterone therapy can also be helpful for perimenopause, heavy periods, endometriosis, adenomyosis, migraines, and premenstrual mood symptoms, including PMDD.
In conclusion, cyclic progesterone therapy is potentially beneficial for PCOS. It can be safely combined with other PCOS treatments, such as metformin, spironolactone, and inositol. Ask me in the comments.
