Blog of the Society for Menstrual Cycle Research

Hot Flash—Progesterone is an Effective Alternative to Estrogen

July 19th, 2010 by Elizabeth Kissling

Guest post by Jerilynn Prior, Centre for Menstrual Cycle and Ovulation Research

hot flash hellIt’s been two weeks since Chris Hitchcock and I returned from San Diego’s recent Endocrine Society meetings. We are feeling incredibly happy with the success of our protracted, intense commitments to a controlled trial of oral micronized progesterone (marketed in the USA and Canada as Prometrium®) for night sweats and hot flushes/flashes. At the Endocrine Society we presented the first-ever trial showing that the molecularly identical progesterone by mouth is effective treatment for vasomotor symptoms (VMS = hot flushes/flashes and night sweats)(1). We were also invited to present our data at an Endocrine Society-sponsored press conference.

Why did a scientific study require so much from us? First, this trial started in 2003 as the initial scientific venture of the newly founded Centre for Menstrual Cycle and Ovulation Research–thus CeMCOR’s reputation became tied to this trial. Second, despite concerted efforts, we were never able to obtain peer reviewed funding for this study—we successfully supported it with individual private donations. Finally, because of the “estrogen myth” and its corollary negatives about progesterone, I wanted to gain additional accurate information about how Prometrium® works in women’s cardiovascular system from this same study. For that reason we decided to enroll only very healthy women who were within 1-10 years since their final flow—they had to be non-smokers, without obesity, diabetes, or high blood pressure, and further to have normal measured waist circumference, blood pressure, cholesterol, and fasting blood sugar levels. Therefore many women were interested but few were eligible.

Late last fall when we broke to code on this study, we were ecstatic to discover that our trial was highly successful. After only three months’ therapy with Prometrium® (300 mg at bedtime daily) the 127 (of 133 randomized) women’s vasomotor symptoms score (VMS Score, combination of number of flushes times their intensity during the day and during sleep) was decreased by about 60% on progesterone compared to less than 30% decrease on placebo.

In early June we learned the answer to another important question: Does progesterone effectively treat intense VMS? The answer is yes! Although less than half all the treatment-seeking women in our study met the FDA’s criteria for more than 50 moderate-intense VMS/week, the 30 women who did who were randomized to Prometrium® showed significantly more improvement in hot flushes than did women on placebo.

What were the reactions to this news? Some local doctors said they already knew that progesterone was good for VMS! Others people were curious, or skeptical but many realized the importance of providing women with an effective alternative to estrogen for VMS. Other reactions were predictable—many questions about whether this couldn’t really be explained, somehow, by estrogen (Prometrium® is converted into estrogen—not!). And there were several questions about side effects and alleged serious health risks from progesterone (wrongly attributed because of confusion of progesterone with synthetic progestins). Happily I was able to respond that participants had no serious negative effects—more placebo-treated than Prometrium®-treated women dropped out before completion. And it is likely that in estrogen-treated women progesterone decreases breast cancer risk rather than increasing it as medroxyprogesterone does (2). Because of Prometrium®’s significant sleep benefit (3), some women who entered the trial sleep-deprived experienced short-lived morning drowsiness. But the estrogen myth-related mood, bloating, weight gain, migraine headaches, and breast tenderness did not occur.

An epic journey for me, Chris, and CeMCOR ends in triumph. Now that the dust has settled, I am so grateful that CeMCOR’s many researchers over the last six years dedicated themselves to a world class trial, that local donors made the trial possible, and that the Prometrium® and placebo were provided by Schering Canada (for the first two years) and subsequently by the world-wide manufacturer, Besins Healthcare of Belgium.  Continue reading...

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Posted in Menopause, New Research, Pharmaceutical | 1 Comment »

Hooked on Estrogen

May 13th, 2010 by Elizabeth Kissling

Guest Post by Jerilynn Prior, M.D.,  Centre for Menstrual Cycle and Ovulation Research

Estrogen moleculeYes! I’m sure you can hear my whoop of excitement and vindication. Finally, something negative about estrogen and positive about progesterone in the mainstream media. According to this article by Emily Anthes in the current issue of Scientific American: Mind,  women’s risk for addiction, and potential for successful withdrawal, are both linked to our menstrual cycle hormones. Estrogen increases women’s addictive behaviors while progesterone assists with successful addiction recovery.

Why am I feeling vindicated? Because I recently declared that hot flushes/flashes and night sweats are estrogen addiction (1). That wild but supportable hypothesis is based on the evidence that prolonged or high-dose estrogen exposure is required for hot flushes to occur. But, it is the subsequent abrupt decrease in estrogen levels that triggers vasomotor symptoms. Drug exposure—drug withdrawal symptoms. And do women feel high on estrogen? Perhaps. Clearly the withdrawal is miserable—as one woman said, “I continued to take it only because I couldn’t stand being off the hormone. I really couldn’t function.” (p. 2130 (2). Just ask any woman taking estrogen for hot flushes who has tried to stop it.

Rat brains are not the focus of my research—and I generally think rodents aren’t much like women. However, the animal evidence showing that estrogen increases addictive behaviours is strong and extensive. About a year ago I had occasion to visit a recovery facility for women with addictions—it suddenly struck me that most of the women there were perimenopausal. They were experiencing estrogen’s highs and the roller coasters and because normal ovulation is rare in perimenopause they were not having enough progesterone—and battling drug dependence. Sure enough, as Anthes states, hundred of experiments show that female rats become addicted more quickly than male rats, are less likely to become addicted without their ovaries but the quick-dependence problem returns when they are given estrogen (3).

As Anthes reports, it is exciting from animal data that progesterone assists to prevent or treat addictions. However, even more important is the notion that progesterone can assist in addiction recovery—not just in rats but in women. The data strongly suggest that progesterone aids women trying to stop cigarettes (4). Progesterone also appears to decrease the drug “high,” and certain actions of cocaine such as fast heart rate in women who are addicted (5). That was true whether cocaine was administered in the luteal phase (when progesterone is normally high) compared with the estrogen-dominant follicular phase, or when progesterone or placebo were administered to women in the follicular phase (5).

The effect of stress can add another layer of understanding to the addiction arena. We know that estrogen amplifies the responses of the stress hormones ACTH, cortisol and norepinephrine to social stress (ironically, based on a randomized, placebo-controlled trial in men) (6). Could that be one of the reasons estrogen increases women’s addiction susceptibility? It is known but rarely discussed that stress makes both addictive behaviors and hot flushes worse. Progesterone’s positive role in both addictions and hot flush treatment may be because of its effects to improve sleep and decrease anxiety. Two different randomized, placebo-controlled, double masked (neither researchers nor participants knew the identity of the pills) trials show that oral micronized progesterone (Prometrium—300 mg at bedtime) improves sleep without a morning hangover (7), and decreases anxiety in women with premenstrual symptoms (8). These actions may play important roles in progesterone’s potential use as a treatment for addictions and for hot flushes.  Continue reading...

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Posted in anatomy, magazines, Menopause, New Research | 4 Comments »

Neurology and steroid hormones – where is progesterone in this discussion?

April 23rd, 2010 by Chris Hitchcock

Recently the New York Times published a long article entitled the Estrogen Dilemma. It’s an article rich with many issues, and previous blogs have critiqued its uncritical acceptance of the timing hypothesis, and its failure to distinguish between the transient symptoms of perimenopause, early menopause, and the rest of your long, healthy, post-menopausal life.

But it is quite remarkable to me that, when speculating about potential hormonal treatment for poor memory and issues of staying on task, the only steroid hormone that seemed to be on anyone’s radar was estrogen. The writer had a lot of space (7600 words) and gave the scientist a lot of freedom to speculate, so I’m guessing that the absence of progesterone in the article is a true representation of her conceptual blind-spot. Progesterone was mentioned a few times, in the context of protection from uterine cancer, and in the context of using MPA (a synthetic relative) as a possible scapegoat in interpreting the WHI randomized hormone therapy trial data. But never did I see any suggestion that progesterone might be anything other than a necessary evil.

In fact, there are some intriguing new research areas that look at progesterone as therapy in neurological domains.

So, in a free-wheeling article about how scientists are exploring possibilities, it’s interesting that the possibilities seem to be limited by a cultural bias towards estrogen.

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The Great Perimenopause Cover-Up

April 19th, 2010 by Elizabeth Kissling

Guest Post by Jerilynn C. Prior, Centre for Menstrual Cycle and Ovulation Research

I just read “The Estrogen Dilemma” in Sunday’s New York Times Magazine,  and I feel like weeping—in sorrow and deep sadness. This article by Cynthia Gorney is about energetic, intelligent women who feel they must take estrogen in order to survive perimenopause yet have deep worries about its risks. I know personally the anguishing changes that erupt during perimenopause. “The Estrogen Dilemma” also evoked my frustration and even rage. It is wrong that symptomatic women in the midst of the long and stormy midlife transition have to face a conundrum—to take estrogen or not. It arises from a Nixonian-style cover-up of three proven and important-for-women truths: 1)    Perimenopause causes higher and not lower estrogen levels. (By perimenopause I mean the transition from fertile menstrual cycles to menopause, or the life phase beginning one year beyond the final menstrual flow.) 2)    Progesterone, estrogen’s essential partner hormone, in contrast to estrogen, truly is lower in perimenopause. 3)    Women survive perimenopause and “graduate” into a less symptomatic menopause.

Are estrogen levels low in perimenopause? No. Taking all perimenopausal women together (a meta-analysis of published levels comparing within-center young with perimenopausal women) estrogen levels are 26 percent higher (1). For symptomatic perimenopausal women like Cynthia Gormley and myself, estrogen swings to Everest-like peaks and may intermittently be a 1000-fold greater. Perimenopause, for some of us, is estrogen’s storm season (2).

Despite that, ever since estrogen was first discovered in 1926, anything ailing women has been deemed “estrogen deficiency.” And often inappropriately so treated. Thus, estrogen levels must be dropping and low in perimenopause when women become symptomatic—it makes sense because we know that perimenopausal women are running out of their store of ovarian follicles that, after all, make estrogen. That perimenopause-dropping-estrogen idea fits with the fact that perimenopausal women begin to have night sweats. But it doesn’t fit with the reality that night sweats begin while women are still having regular menstrual cycles (3) and thus still have adequate estrogen levels (but the misunderstanding of what causes hot flushes is yet another story).

The evidence that perimenopausal estrogen levels are higher than in the sexiest 20-something is strong and consistent (1;4-9). Why are media articles, consensus documents and authorized definitions still talking about dropping estrogen levels? A cover-up. The first clear evidence for higher estrogen was published from a Melbourne epidemiology study in 1995 (10). The back-story here is telling—the authors measured estrogen levels that were variable but at least a quarter of them were much higher than expected. However, their interpretation was that estrogen levels were dropping. That’s because levels in the 45-55 year old women with regular cycles (whom they wrongly called premenopausal) were higher than in those who’d been without flow for three to 12 months (10). That illustrates the power of what I call “the estrogen myth.” I, who at the time was suffering with puzzling sore breasts, heavy but regular flow and mood swings, was ecstatic to see data that explained my experiences. However, I was horrified at the erroneous interpretation—my colleagues and I wrote an impassioned letter to the editor demanding that the authors “let the data speak” (11).

Now to the second cover-up—lower perimenopausal progesterone. If this were a world where women’s health was guided by science rather than by power-over-women, we would all know that perimenopause, besides being a time of higher estrogen, is a life phase in which progesterone is too low. You ask, “Why are lower progesterone levels important? I thought it causes PMS and breast cancer.” This ignoring or blaming of progesterone is the second major cover-up, and not just for 15 years, but since estrogen’s discovery in the 1920s. Framing women’s reproduction only in terms of estrogen creates the postulate that “Estrogen’s what makes a girl, a girl.” The estrogen myth further asserts that estrogen is the female hormone, much as testosterone is the only important male hormone.  Continue reading...

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Posted in Menopause, New Research, Newspapers, Pharmaceutical | 2 Comments »

Bioidentical Balderdash

January 1st, 2010 by Chris Hitchcock

The bioidentical hormone therapy industry has been getting a bad rap lately in the US, and this press release is an example of why. Among other things, the writer confuses estrogen and progesterone, in one paragraph saying their product is a “safe and scientifically-proven, all-natural estrogen delivery cream[]“, and in the next describing it as a “natural progesterone cream” (emphasis is mine). Moreover, the press release springboards from another estrogen-positive press release that claims that estrogen may be the cure for female depression, citing an ob/gyn author of a book, and promoting a soon-to-be-launched web page.

So, in one breath the product is an estrogen delivery cream that will help with low estrogen, but in the next breath (on the linked product page) it is argued that it will help with estrogen that is too high (which is more accurate). The product website emphasizes that  it is “without dangerous pharmaceuticals”:

This remarkable product contains NO risky synthetic estrogens or progestins. [Product] Cream is similar to the progesterone your body naturally produces, so there are no worries about dangerous interactions or nasty side effects.

It’s been said that there are no side effects, there are just effects. It is odd to marry this claim that their product won’t have nasty side effects (because it is like the progesterone in your body) with the claim that progesterone cream will balance out the nasty effects of your own high estrogen levels.

Progesterone cream may well be better tolerated, but just because it’s natural, doesn’t make it so.

And, interestingly, despite being anti-big Pharma, the article adopts the pharmaceutical industry’s language of menopause as “estrogen deficiency” that has been so helpful to those who would market “hormone replacement therapy” as a cure for all female ageing. As is still common, it is assumed that perimenopause (the transition leading up to the last period) is a time of dropping estrogen. There’s also the assumption that the challenging issues of midlife are necessarily hormonal (rather than multi-faceted, including not only biological changes, but also cultural views of ageing, social context, socioeconomic issues, divorce-related poverty, even spiritual and psychological development).

It’s unfortunate that bioidentical has come to be associated with fuzzy thinking and poorly supported claims, because there are good, solid, well-researched arguments in favour of using naturally occurring molecules for therapy, particularly for hot flushes and night sweats. We’re analyzing data from the first randomized placebo-controlled trial of oral micronized progesterone for hot flushes and night sweats in early menopause, and we should have some data later this year to report.

It’s also worth noting that other countries do it differently – Canadians can buy progesterone cream such as this, but they do it with a prescription, at a specified dose, and for a particular issue. And people who try to sell it over the counter in a health store are prosecuted.


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Taking Women’s Health Seriously

December 8th, 2009 by Elizabeth Kissling

Here’s one way that Canada shows some concern for risks to women’s health: the owner of a New Brunswick health food store was fined $7500 for smuggling a progesterone-laced cream from the U.S. The cream, called Aim Renewed Balance, is purported “to help restore balance between the hormones that cause premenstrual syndrome and menopause symptoms, such as hot flashes and mood swings.” It is not approved for use in Canada.

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Hot Flushes Relief Needn’t Enter the Bio-Identicals Fray

November 5th, 2009 by Elizabeth Kissling

Guest Post by Jerilynn Prior, Centre for Menstrual Cycle and Ovulation Research

pharmacy_clipAs a clinician scientist with expertise in hormones and women’s health, I sit in Canada and look at the hype and dis-sing going on about “bio-identicals” in the USA and shake my head. If we don’t want estrogen that is not FDA approved to be used to treat hot flushes, the simple answer is to regulate appropriately. The perpetual debate about bio-identical hormones has now hit USA Today with a headline: “Bioidenticals: Estrogen without FDA approval for menopause?”

In Canada, all hormonal preparations require a prescription. Full stop.  And the pharmacists who compound estriol or progesterone do so with my prescription for a specific dose and clear purpose. Those compounding pharmacists are also regulated the same way as pharmacists who dispense FDA/Health Canada approved medications. End of story.

What bothers me is that I believe there is an intrinsic advantage to  hormones that are molecularly the same as our bodies produce. They are certainly better, a priori than those that are natural for horses or are “similar-but-different.” When oral micronized progesterone (molecularly identical, Prometrium®) is prescribed with estradiol (there are multiple FDA-approved brands of molecularly identical estrogen), there is no increased breast cancer risk.[1] On the other hand, medroxyprogesterone (a similar synthetic derivative of progesterone) with estradiol increases the risk for breast cancer by 79%.[1] That’s called a nasty surprise.

When a hormone treatment is the same as a native hormone we know exactly how it will act, be metabolized, and be excreted. We can learn, if we don’t know, how it interacts with other important factors like age, weight, kidney function, and in relationship to heart disease or breast cancer. So the fact that Wyeth “suggested” that the FDA take compounding and bio-identical hormones to task for false advertising, was simply an effort to regain market share in a legal drug war. They were reeling from the negative results of the Women’s Health Initiative. That’s why they also planned, wrote and published monthly Premarin-positive or estrogen-positive editorials and reviews in house at Wyeth and had them ghost authored by prominent scientists. A turf war.

As a physician, I believe the best treatment for severe vaginal dryness causing repeated bladder infections in older menopausal women is vaginal estriol in a dose of 0.5 mg twice a week.[2] However, there is no FDA/Health Canada approved estriol product. It’s just not available. So, I can prescribe that estriol—the weakest of the three estrogens our bodies make—and a local compounding pharmacist will make it for my patient. And that is a dose and kind of estrogen hormone that doesn’t cause a risk for endometrial (uterine lining) overgrowth or cancer as Premarin cream can (especially if delivered with that ridiculous vaginal applicator and in the doses that are commonly recommended).

What makes me feel both sad and angry is that this bio-identical “tempest in a teapot” (as my grandmother would say) is ignoring the distress of women with severe hot flushes. They are the reason for the popularity of compounded hormones, of the “experts” like Suzanne Somers and those who publicize and back her exuberant and likely imprudent self-medication. I have been cheering since Dr. Leonetti showed that 20 mg twice a day of progesterone cream significantly improved hot flushes.[3] If compounded hormones are evidence-based, as estriol and progesterone cream are for the conditions mentioned, who would fault women for wanting them? Especially when there is sufficient reason to doubt the hormone promises of Big Pharma?  Continue reading...

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Readers should note that statements published in re: Cycling are those of individual authors and do not necessarily reflect the positions of the Society as a whole.