Menopause / PCOS: Estrogen Loss and Aging

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Dr. Mark Perloe:  “This is Dr. Mark Perloe, and I’m here with Dr. Geoffrey Redmond at the Center for Health Research and the Women’s Hormone Center in Cleveland, Ohio.  Your presentation reviewed the issues surrounding PCOS and menopause.  Do we need to be concerned about polycystic ovary syndrome in a time when the ovary really isn’t functioning anymore?”

Dr. Geoffrey Redmond:  “It’s an important question because every woman with PCOS is going to go through menopause so it’s an unavoidable event that we need to give attention to.  We can’t assume that that event is the same for women with PCOS as it is for other women.  The most important point is that although the name refers to the ovary, the condition is a systemic one; it involves other systems.  Just because the ovaries are not functioning as much doesn’t mean that the other abnormalities won’t still be present.  Of course, we’re particularly concerned as women get older about cardiovascular health and so we need to check these women for insulin resistance, for unfavorable lipid patterns and hypertension, all of which seem to be increased in the older woman with PCOS.  Additionally, some of the troublesome appearance changes like hirsutism may persist, and hair loss or alopecia often gets worse peri-menopausally.  So even though the ovaries may have slowed down or may have been removed surgically, the condition still persists.” 

Dr. Mark Perloe:  “What about with hysterectomy, is that a factor in how we have to look at this?  Have we taken care of the condition if a hysterectomy has been carried out?”

Dr. Geoffrey Redmond:  “Absolutely not, we certainly removed one of the risks which is endometrial cancer but the other risks, as I say, for metabolic problems in the skin and hair changes which doctors often don’t focus on but the patients certainly do, those are likely to persist with or without ovaries.  So total abdominal hysterectomy for PSO does not stop the condition.”

Dr. Mark Perloe:  “One of the things that we know happens with menopause, and you showed in your slides, is that just about every androgen known to man will decrease as the woman goes through menopause yet at the same time she’s complaining of increasing hirsutism.  Why is that, and what ought our approach be to help her deal with the complaint of hirsutism?”

Dr. Geoffrey Redmond:  “As you say, our studies and those of other people clearly show that testosterone, androstenedione, DHEA, and DHEAS levels climb fairly sharply with age.  After menopause, most have low levels of testosterone, and a few with an uncommon condition called hyperthecosis have very high levels but that’s a small group with different kinds of problems.  However, what the hair follicle reflects is not necessarily the momentary androgen level but the long-term exposure to androgens.  It seems that androgens kind of prime the hair follicle so once it’s become more active as a result of exposure to testosterone, it continues to be more active and, therefore, hirsutism does not necessarily go away just because the androgen levels decline.”

Dr. Mark Perloe:  “What are the implications when we’re treating hirsutism in a younger level?  We put the woman on a pill or on spironolactone in combination with the pill, when are we going to start seeing changes?”

Dr. Geoffrey Redmond:  “First, in younger women there’s a little more chance that testosterone will be elevated but many hirsute women do not have high testosterone.  However, it’s very important to understand that testosterone is always the cause of hirsutism.  Without testosterone action, there’s no hirsutism.  It may be that some women have very sensitive follicles so a normal level of testosterone will give her much more hair growth.  As you’re alluding to in your question, it’s not entirely reversible; once the hair follicle gets active, it tends to stay active.  For example, in men who have their testicles removed for prostate cancer or whatever, they have a lot less hair growth but they don’t go back to looking the way they did when they were eleven in terms of facial hair.  So because it’s not completely reversible, I think early intervention and treatment with, as you suggested, birth control pills which will cut free testosterone levels about in half usually, and an androgen antagonist is appropriate not only to treat the problem as it is then but to lessen its progression and worsening.”

Dr. Mark Perloe:  “You talked at your luncheon conference about a new medication that may be available to address this situation where the hair follicle has been primed already and androgens may no longer be an issue.  Could you speak to that new opportunity?”

Dr. Geoffrey Redmond:  “The clinical trials on this new compound, Eflornithine, have been completed and they’ve been submitted to the FDA so we’re waiting for the FDA’s word on that.  But this compound has a different mechanism; it inhibits ornithine-D carboxylase, which is involved in hair growth.  It stops the hair growth process past the androgen step, it simply inhibits the activity of the hair follicle and, therefore, it slows down hair growth.”

Dr. Mark Perloe:  “Have any trials been done in combination with other approaches or do you see rationale for combination therapy?”

Dr. Geoffrey Redmond:  “I don’t think we know that.  Like most clinical trials, other drugs that might confuse the picture were excluded so somebody wouldn’t have been allowed in if they were on any antiandrogen or any other medication that might affect hair growth.  So we really don’t have any experience as to whether other things would add to efficacy.  Assuming the FDA approves it, it will be the only approved drug for treatment of excessive facial hair in women.  Whether other drugs added to it off label would be helpful or not, I think at this point is speculation.”

Dr. Mark Perloe:  “The medication would appear to be effective while you’re taking it according to the photos that you had shown.  Once a woman stops, what would be the expectation?”

Dr. Geoffrey Redmond:  “The clinical trials consisted of 24 weeks of administering the active Eflornithine or a placebo blinded course and then an 8 week watch out period.  At the end of that 8 weeks, the hirsutism had recurred to some degree so it would appear that one needs to use it continuously in order to keep getting the benefit.”

Dr. Mark Perloe:  “How is this marketed, and how is it used?  How often during a day does a person use it, and are they going to use it on their whole body?  What are the questions that patients are going to want to know?”

Dr. Geoffrey Redmond:  “The study was designed to answer whether it was safe and effective for facial hair growth.  So using it on other areas of the body, particularly covering more extensive area where more might be absorbed, is really something where the safety is not addressed by the data so it’s certainly not going to be recommended.”

Dr. Mark Perloe:  “We look forward to hearing more about that, and thank you so much for stopping by and talking with us.”