A Patient With PCOS
Cindy, a 34 year old flight attendant had been taking birth control pills for 17 years because of PCOS (Polycystic Ovary Syndrome). The chief complaint was acne and hirsutism from high testosterone levels, for which the birth control pills had been prescribed. Cindy had married a year ago, and was now ready to start a family, so she had discontinued the birth control pills on her own a few months before arriving to my office. Cindy had one normal menstrual period in the last four months since stopping the BCP’s. Cindy came for an office visit because she wanted a treatment that would restore normal menstrual cycles, fertility, as well eliminate the excess facial hair, acne and other androgenic effects of elevated testosterone levels.
Laboratory workup showed absent progesterone production on Day 19 of her cycle indicating anovulation. Her DHEA and testosterone levels were mildly elevated. Baseline 17 hydroxyprogesterone was normal. Treatment was started and three months later Cindy called to report that she was pregnant.
Treatment program for PCOS to induce ovulation:
1) Treatment was started with progesterone twice a day for days 12-26 of the cycle.
2) Metformin 500 mg tabs twice a day with meals.
3) Clomid 50 mg tabs for 5 days on days 3-7 of the cycle.
4) If the above is ineffective at inducing ovulation, Dexamethazone 2 mg per day for days 3-12 of the cycle.
The defining hallmark of PCOS is lack of ovulation, which in turn causes progesterone deficiency. Progesterone for PCOS was pioneered by John R Lee MD who wrote extensively about his experience treating PCOS with cyclic progesterone. This is covered in Part One of this article. Cyclic progesterone is thought to reset the hypothalamic-pituitary axis which controls ovulation, thus helping restart normal ovulation in the PCOS patient when taken over a 3-6 months of use.
Progesterone inhibits the enzyme that converts testosterone to its stronger metabolite, DHT), and thus may reduce hirsutism and serve as an anti-androgen. Spironolactone, (Aldactone 50 mg BID) another commonly used drug used as a blood pressure pill, diuretic pill, and also has anti-androgen effects, it inhibits 5 alpha reductase conversion of testosterone to DHT, and is commonly used to treat hirsutism in PCOS patients.
Metformin is an extremely helpful drug for PCOS patients, and should be considered as the first line of treatment. In obese women with the polycystic ovary syndrome, decreasing serum insulin concentrations with metformin reduces ovarian cytochrome P450c17 alpha activity and ameliorates hyperandrogenism. Metformin may decrease B12 levels, so make sure you take extra B12 supplements with your Metformin.
Some cases of anovulation are the result of a genetic enzyme deficiency in the adrenal gland with inadequate conversion of 17 hydroxyprogesterone into cortisol. This leads to overproduction of androgenic hormones such as DHEA and Testosterone. This genetic abnormality may be associated with anovulation and hirsutism in a clinical presentation which may mimic PCOS. In this scenario, Dexamethasone may be added to the Clomid. (Dexamethasone 2 mg per day for days 3-12 of the cycle.)
The Dexamethasone inhibits ACTH production by the pituitary and prevents the adrenal from making excess testosterone, and is in fact curative of the hirsutism and acne symptoms, and in many cases restores ovulation and fertility.
Clomiphene is the first drug of choice to induce ovulation in the PCOS patient. Clomid blocks the estrogen receptors in the hypothalamus, causing an LH, FSH surge, which induces ovulation. Clomid is usually given over 5 days during the luteal phase of the cycle, for days 3-7 or 4-8 at a dose starting at 50 mg per day. This may be increased by 100 mg if the lower dosage is unsuccessful and fails to induce ovulation.
OCP’s, Birth Control Pills and other Synthetic Hormones
OCPs are commonly prescribed to the PCOS patient to mask the androgenic symptoms of acne and hirsutism. This form of therapy is ill advised and misplaced, since it does not address the underlying problem of lack of ovulation with disordered hormone production. In other words, OCPs are symptomatic treatment which does not address the root cause of the problem, which is anovulation with imbalance in ovarian and adrenal hormone regulation. OCP’s further suppress and prevent ovulation, rather than restore this normal physiological function in the female.
The reader is advised to discuss the comments on these pages with his/her personal physicians and to only act upon the advice of his/her personal physician. Also note that concerning an answer which appears as an electronically posted question, I am NOT creating a physician — patient relationship. Although identities will remain confidential as much as possible, as I can not control the media, I can not take responsibility for any breaches of confidentiality that may occur.
This is Part Two of a Series, For Part One, Click Here and to read this article with full references please visit http://jeffreydach.com/2012/06/20/pcos-part-two-clomid-and-metformin-by-jeffrey-dach-md.aspx
There is a newly formed support group http://pcoscysterhooduk.org/Home_Page.php looking into the effects of PCOS. They aim to provide information about the condition and its effects and treatments while hopefully raising funds to do in-depth research into the condition and help women get the treatments they need, this support network is run by PCOS sufferers.