Dr. Jerilynn Prior is a Professor and physician at the University of British Columbia and Celeste Wincapaw is a Vancouver woman and member of the Community Advisory Council for the Centre for Menstrual Cycle and Ovulation Research. Because Celeste is interested for personal reasons and has questions about “polycystic ovary syndrome” (also called PCOS but which CeMCOR calls Anovulatory Androgen Excess or AAE) they decided together to explore new and helpful information about this mysterious condition.
Celeste: Why do you use the term Anovulatory Androgen Excess (AAE) instead of Polycystic Ovarian Syndrome (PCOS)?
Jerilynn: For a start, PCOS puts the focus on cysts in the ovary rather than on the lack of ovulation that is the real problem when women have unwanted facial hair, acne, far-apart periods and head hair loss. Ovarian cysts do not make a disease! Ovarian cysts are simply round cavities filled with fluid that are present in any woman who doesn’t release an egg each menstrual cycle. All that the presence of cysts on an ovary ultrasound mean is that a woman’s reproductive system is out of balance temporarily and not releasing eggs.
I use the term “Anovulatory Androgen Excess” (AAE) because it focuses on the key issues for women. These include trouble releasing an egg (ovulating, called “anovulation”), periods farther apart than 35 days (officially called oligomenorrhea), difficulties with getting pregnant, unwanted facial hair (hirsutism), pimples (acne), thinning of head hair (alopecia), and sometimes sugar cravings or being overweight. Usually the diagnosis is clear if there are any signs of excess male hormones and changes in the menstrual cycle and ovulation.
Celeste: Is AAE inherited? And if so, can there be anything done to help women with AAE?
Jerilynn: Yes, AAE is genetic but it is highly treatable. Women can have children, eliminate blemishes, reduce facial hair and lower their risk for developing insulin resistance, type 2 diabetes (a disease of adults in which blood sugars are too high because insulin is not working effectively) and heart disease. AAE is thought to lead to insulin resistance through inherited risks for it and to heart disease because of the increased risks for diabetes and the negative effects of the male hormones on cholesterol and blood vessels. Although the treatment is complex and involves exercise and healthy eating plus several therapies taken over long periods of time, I’ve worked with women for many years and seen them improve and even be able to stop therapy.
Celeste: That’s news to me! Are you doing something I’ve not read about?
Jerilynn: I use cyclic progesterone therapy as the heart of treatment for anovulatory androgen excess.
Celeste: Why do you do that?
Jerilynn: Progesterone is the hormone made by the ovary after an egg is released. The fundamental problem with AAE is not making progesterone for two weeks every cycle. This lack of progesterone leads to an imbalance in the ovary, causes the stimulation of higher male hormones and leads to the irregular periods and trouble getting pregnant. Progesterone is usually missing—replacing it therefore makes sense.
Progesterone talks back to the hypothalamic and pituitary (brain) hormones that control the ovary, and stops them from stimulating the ovary to make too much testosterone. Taking progesterone for two weeks every month (called cyclic progesterone) may help the brain to develop the normal cyclic rhythm that is missing in AAE. Progesterone also counterbalances the steadily high estrogen levels that the AAE ovary produces even if you have no periods. Progesterone will prevent estrogen over-stimulation of the uterine lining (endometrial hyperplasia) and heavy flow. It may also interfere with the action of high estrogen on the breasts, therefore preventing tenderness and “lumpiness” and perhaps even the risk for breast cancer.
Finally, and most doctors don’t realize this, progesterone antagonizes and inhibits the enzyme (called 5-alpha reductase) that is needed to make testosterone into dihydrotestosterone. Dihydrotestosterone is the powerful male hormone that talks hair follicles into making coarse hair and too much oil that causes acne.
Celeste: Wow! Why have I never heard of progesterone therapy for AAE before?
Jerilynn: I don’t know why except that progesterone is commonly ignored. I think 25 years ago I started using cyclic progesterone because I wanted to see if women with AAE would have regular periods.
Celeste: The Pill has a manufactured kind of progesterone in it—does that work for AAE treatment?
Jerilynn: Although the Pill does help women with AAE to some degree, my goal for AAE is to return the brain-pituitary-ovary system to a normal balance. The goal of the Pill is the opposite—it must suppress the brain-ovary system to prevent pregnancy. To be able to suppress the system, the Pill contains high dose estrogen, and a synthetic and often male-hormone-like progesterone derivative (progestin). Although the Pill (especially Diane-35 a pill with an anti-male hormone progestin in it) will often help with hirsutism, it doesn’t help to restore that basic balance for women with AAE. (Obviously the Pill is not desirable for older women with AAE or for any women who smoke because of its increased risks for blood clots and strokes.)
Celeste: If I wanted to start using cyclic progesterone treatment how would I begin?
Jerilynn: First of all, your doctor must decide it will help you and provide you with a prescription. The Cyclic Progesterone Therapy handout [1] [1]tells you and your doctor exactly what you need to know.
Along with our conversation here that will provide information for women, I am gathering data and writing an article for physicians that I will soon post on the Health Care Provider portion of this website. At present I am using information I’ve gathered from many studies and relying on my long experience taking care of women with AAE. In the future I’m also hoping to do research with specialists in dermatology to compare the usual therapy with my approach to prove that what I’m suggesting here is both effective and safe.
Celeste: You mentioned you use several therapies, what are the others besides cyclic progesterone?
Jerilynn: The second key therapy after cyclic progesterone is aimed to block the action of that dihydrotestosterone hormone in hair follicles. The medicine I use is called spironolactone. It is a drug that was designed as a blood pressure pill to block the salt-retaining hormone, aldosterone. It turned out to also be a strong blocker of male hormones (anti-androgen). Because humans have been treated with it for over 30 years, we know that it is safe and effective. It has similar anti-androgen actions as the medicine called “cyproterone acetate” that is in the Pill called “Diane-35â.”
Spironolactone is now generic and costs about fifty cents for a 100-mg pill, which is the usual daily dose. This medicine doesn’t cause the blood pressure to go too low in people with normal blood pressure. Its major side effect in women is that it causes irregular and frequent periods that are prevented by also taking cyclic progesterone.
Celeste: What changes and experiences could I expect if I took cyclic progesterone and spironolactone for three months?
Jerilynn: It takes a long time for the face hair follicles to learn to make coarse, dark hair. Therefore it also takes a long time for them to forget how! In three months you would already see that acne and pimples were controlled, and you would also see that the facial hairs are starting to thin. It takes about six months before facial hairs begin to become less coarse or dark. It takes many years before they disappear altogether. The first places that hair disappears are in the sideburns, arms and legs and under the arms. The slowest and most stubborn places are on the inner thighs and at the point of the chin.
Celeste: What if I wanted to use electrolysis or laser therapy so I would feel better about how I look while these medicines do their work?
Jerilynn: Laser and electrolysis therapies are a good idea because the hair changes from these hormonal therapies take a long time. It is important to know that laser therapy doesn’t work if your unwanted hair is blond. Also, be careful to choose a skilled and highly recommended person to do electrolysis because otherwise it can cause pitting of the skin. You also want to be absolutely sure that an HIV prevention protocol is followed.
Celeste: So I could do some laser and also start cyclic progesterone and spironolactone. But first I need to know whether there any side effects from spironolactone.
Jerilynn: Some early safety studies with spironolactone showed an increased risk for breast cancers in beagle dogs. We now understand that that is a genetic risk specific to that breed and not relevant to women.
In the first weeks of taking spironolactone it acts as a water-pill (diuretic) and will make you urinate more. That’s a bonus to women who want to lose weight! That diuretic effect goes away, but nevertheless I caution women to drink enough water and avoid dehydration.
We initially learned about spironolactone’s anti-androgen action because men treated with large doses for high blood pressure had decreased sex drive and developed bigger and sore breasts. Blocking male hormones may allow women’s breasts to “grow up” if they are not mature. In my experience, with the lower doses most women need and lower than were used in men, breast tenderness and enlargement are not problems.
Celeste: We know that diabetes is a health risk related to AAE. I can see health and beauty in women of all sizes. I also keep hearing about the heart health risks of being an overweight, apple-shaped person. How does a large, apple-shaped woman with AAE decrease her risks for developing diabetes?
Jerilynn: Happily we now know that regular, moderate exercise can prevent diabetes. I have a close relative with diabetes so that is a message I also take to heart!
But all of us need reminders to live healthily and be active! I always ask my patients what exercise they are regularly doing. I also remind them and myself that 30-minutes a day of walking or other activity is perfect.
As a way we can monitor our own risks for insulin resistance (meaning our bodies are making too much insulin, but it isn’t working very well) I suggest measuring waist circumference. A waist circumference of over 88 cm (about 33 inches) in women has been associated with insulin resistance. As insulin levels get higher and do not work as well, fat begins to accumulate in our abdomens.
The good news, bringing us back to exercise, is that muscle activity allows sugar to get into cells, makes insulin levels go down and decreases our food cravings. Often exercise will also eliminate belly fat and decrease waist circumference before any general weight loss. I’ve seen my own waistline decrease several centimetres without any change in weight.
If a woman with AAE has a waist circumference over 88 cm or a relative with type 2 diabetes, I also ask her to get a fasting blood sugar test every six months.
Celeste: For me, as a large, apple-shaped woman with AAE, it would be detrimental to my health to measure my waist! I see it as an emotionally loaded action that will show that I don’t measure up to our society’s idea of what a normal, healthy woman should be. The key ways I cope with AAE are to refuse to trigger my self-loathing by weighing, measuring, or dieting. Instead, I focus on being fully present, self aware, and mindful of my own internal compass.
Jerilynn: I value your honesty about my enthusiastic suggestion. It’s just that I’m the kind of person who wants to do something. Seeing that my waist is not getting bigger or is gradually shrinking is a satisfying reinforcement for me to keep exercising and trying to avoid sweets.
Celeste: Ok, I’ll admit there are different ways we as women approach our lives. I also think women as a whole, particularly large women, need no encouragement to link their a sense of emotional well being to a number on a tape measure or a scale. The bigger challenge is to help create opportunities for large people to be active in size-positive spaces. A good example here in Vancouver is the In Grand Form program at the YWCA. I also use the gym and pool late at night when it’s not so busy. Speaking of exercise, do you have any additional suggestions for women who are both fit and fat?
Jerilynn: Although regular exercise is the single most important thing to do to decrease the risk for diabetes by making insulin work better, I might start treatment with metformin if a woman was becoming discouraged at not losing weight. Metformin is a medicine (in pill form) that improves insulin action and decreases insulin resistance. Exercise is stronger than metformin, but together they can be a powerful combination.
Another good news thing is that, while we are taking 300 mg of progesterone a day, we will be burning 300 more calories—we can eat 300 more calories without gaining weight! Progesterone makes us burn about 300 kcal more a day because it takes that much energy to raise our body temperature, as progesterone does, about 0.2 degrees Celsius.
Celeste: What are the pros and cons of metformin?
Jerilynn: Metformin is another of those old medicines that has been widely used and for which its adverse effects are well known. Nausea, decreased appetite and diarrhea are the most common side effects. To decrease these I recommend starting with a low dose. I suggest beginning with half a 500-mg tablet with supper. If that goes well after a few days to a week, then increase to a full tablet at supper for another week. If that amount is well tolerated, the next week add 500 mg at breakfast. Some women may require 500 mg with every meal to a maximum dose of 2000 mg, or two tablets with supper and one tablet at both breakfast and lunch.
Metformin’s side effect of decreased appetite is helpful for many women! Some people on metformin will experience loose bowel movements for a short while. A few women will have sufficient diarrhea that they cannot take metformin. If this happens, a similar, but more expensive medicine called “Roziglitazone” (Avandia) can be substituted in a dose of 4 mg a day.
Celeste: All this new information about AAE is a lot to take in all at once. Can you explain this in a nutshell?
Jerilynn: The basic problem with AAE is an inherited tendency for disturbed ovulation, excess male hormone production and insulin resistance. The therapy that I have found successful is cyclic progesterone that helps counteract and to lower chronically high estrogen levels, balances the ovary-brain feedback, produces monthly cycles and decreases the skin effects of the higher male hormones. The second part of the therapy is spironolactone that blocks the male hormone action at the hair follicles and oil glands. The final part of treatment is regular exercise, good nutrition and avoiding sweets; metformin can be added if needed for diabetes risk and excessive insulin production.
Celeste: Thank you Jerilynn. Talking with you always feels like a great new lesson in endocrinology education.
Jerilynn: Given that medical treatment is just one part of being healthy, what have you learned about having AAE that might be helpful for others?
Celeste: I have felt the entire spectrum of emotions about my AAE body including a bit of self- hatred that has made me feel “never good enough.” Probably my most treasured result of having AAE is that I am learning to trust rather than to try to control my body. It seems like a simple concept but it’s not. I think most women are encouraged to follow someone else’s “top ten tips” rather than to dig deep into themselves to find what they intuitively know about what makes them healthy. For me that has meant whole, natural foods, love, friendship, and an unwavering commitment to physical activity. I reduce my exposure to unrealistic images by getting rid of my cable TV and hanging out with other powerful, active, large women. I also refuse to either make a big deal of or hide the fact that I have embarked on a life-long personal diabetes prevention project.
Jerilynn: Me too! What helpful resources have you found about AAE that you want to share with others?
Celeste: There’s an amazing American website www.pcosupport.org [2] with resources, places to chat, and even a yearly conference. I also like the common sense approach toward healthful food shown in naturopathic medicine and have enjoyed www.ovarian-cysts-pcos.com [3], a website by Nancy Dunne, a Montana naturopath who specializes in PCOS. I also like www.doctormurray.com [4], a website with good stuff about diabetes prevention by another American naturopath, Michael Murray.
Jerilynn: Thank you for that useful information.
Celeste: Recent publicity is increasing the warnings that AAE increases a woman’s risk for heart attack and death from bad things like heart attacks, diabetes and breast cancer. Do you agree?
Jerilynn: I really don’t know. There is one long (30 year) follow-up study of patients looking at causes of death. It did not show an increased risk for death from heart attack but did show increased death related to diabetes and also an increased risk for breast cancer. I guess the best answer to your question is to say that we need more and better research to know what health risks really are associated with AAE. Most women with AAE should have a yearly medical check up for blood pressure, weight, waist circumference, breast examination and a lab test for fasting blood sugar.
Celeste: I heard that there is a new Vancouver initiative that will help us learn about health risks related to AAE. Dr. Sheila Pride and others at the University of British Columbia are beginning a registry for PCOS/AAE and want to follow women for long periods of time documenting the true risks. That registry is not yet ready but we will post information about it on this website when it becomes available.
Jerilynn: That’s a good idea. We will look forward to more information about AAE registry.
Celeste: Obviously the best way to deal with AAE is to work hard to prevent problems from developing in the first place.
Jerilynn: I totally agree!
