Nearly every day we receive e-mails from women who ask what to tell their doctor when he or she demands studies proving that natural hormones are safe and effective. Granted, using natural hormones as recommended by Dr. Lee mimics closely what the body would do naturally, and granted there are hundreds of physicians happily using natural hormones safely and effectively, but it’s always good to have studies to point to.

We do have the studies of Helene Leonetti, M.D. showing that progesterone cream reduces hot flashes, and that it protects the uterus from the effects of estrogen. In Issue 4 of the Hopkins Health Watch, I told you about what’s being called the “Bassett Healthcare Study,” led by researcher Anne Hermann, M.D., which showed beyond a shadow of a doubt that progesterone cream is very well absorbed and utilized by the body. Ironically, this study is now being used as a justification for making progesterone cream a prescription item because (surprise surprise) it really works!

Now we have a newly published study from researchers at the College of Nursing and Health Sciences at The University of Texas at Tyler, led by Kenna Stephenson, M.D., which clearly shows that 30 women using 20 mg of progesterone daily, in a cream, had relief of their menopausal symptoms and didn’t have the side effects associated with the progestins such as Provera. The study was published in the November issue of Blood: The Journal of The American Society of Hematology.

According to a press release published on www.womeninbalance.org, Dr. Stephenson said, “In our study, we tested progesterone cream for safety, efficacy and any short term benefits or harmful effects, by looking at biomarkers. Biomarkers will show up right away as an indication of such serious diseases as cancer, heart disease, infections and dementia. With natural progesterone cream, we found no markers for inflammation or clotting-indicators for most of the serious diseases related to use of traditional hormone replacement therapy, like Provera and Prempro.”

Specific Biomarkers Look Good

Stephenson added that in women with higher than normal cortisol levels, there was a marked decline in the level of cortisol to normal range while they were using the progesterone cream as compared to placebo. Stress activates cortisol, and an abnormal cortisol pattern has been associated with an increased risk of heart attacks, cancer, obesity and other diseases.

The study specifically looked at night cortisol levels, and found that these decreased with the use of progesterone. Those of you who have read our interviews with Dr. David Zava of ZRT Lab will remember that high night cortisol is one of the risk factors for breast cancer.

Because PremPro and Provera have been shown to increase the risk of strokes and heart attacks, Stephenson and her team also looked specifically at blood factors that would predispose women to clotting (strokes, heart attacks), and to blood vessel spasm (heart attack). They found that these parameters remained normal in the women using progesterone cream.

“The results of the study are encouraging ,” Dr. Stephenson said, “because it is clinical evidence of the viable option of bioidentical progesterone cream for menopausal women in their search to relieve menopause symptoms.”

The Abstract of the Stephenson Study

Stephenson, Kenna, Price Carol, Kurdowska Anna et al , “Topical Progesterone Cream Does Not Increase Thrombotic and Inflammatory Factors in Postmenopausal Women,” Blood , Volume 104, issue 11, November 16, 2004 .

Postmenopausal women have an increased risk of cardiovascular disease, and heart disease is the leading cause of death in postmenopausal American women. Conventional hormone replacement therapy has been shown to result in an increase in thrombotic events in large prospective clinical trials including HERS I, and the recently halted Women’s Health Initiative.

One possible mechanism for this observed increase is the unfavorable net effects of conjugated equine estrogens and medroxyprogesterone acetate on the hemostatic balance and inflammatory factors. An estimated 50 million American women are peri or postmenopausal and clinical therapies for menopausal symptoms remain a significant challenge in light of the known thrombotic risks.

In this prospective blinded study, we examined the short-term effect of topical progesterone cream on menopausal symptom relief in 30 healthy postmenopausal women. Potential adverse effects of topical progesterone on hemostatic and inflammatory factors and cortisol levels were also examined. Subjects were randomized to first receive either 20 mg of topical progesterone cream or placebo cream for 4 weeks.

Following a subsequent 4-week washout period, subjects were crossed over to either placebo cream or active drug for an additional 4-week period. In each case, progesterone and cortisol levels were monitored by salivary sampling. Baseline values, 4-week follow-up values and end-of-study values were also obtained for the Greene Climacteric Scale, total factor VII:C, factor VIIa, factor V, fibrinogen, antithrombin, PAI-1, CRP, TNFá, and IL-6.

For subjects receiving 20 mg of topical progesterone cream for 4 weeks, Greene Climacteric Scale scores were consistently and significantly improved (decreased) over baseline, demonstrating significant relief from menopausal symptoms.

In addition, in a subpopulation of hypercortisolemic women, topical progesterone was associated with a favorable decrease in nocturnal cortisol. Surprisingly, and in sharp contrast to earlier studies with conventional hormone replacement therapy, topical progesterone had no effect on any of the hemostatic components examined: total factor VII:C, factor VIIa, factor V, fibrinogen, antithrombin, and PAI-1 levels were all unchanged. Levels of CRP, TNFá and IL-6 also remained unchanged.

From this study we conclude that administration of topical progesterone cream at a daily dose of 20 mg significantly relieves menopausal symptoms in postmenopausal women without adversely altering prothrombotic potential. Since the thrombotic complications that are typically observed with conventional hormone replacement therapy do not seem to occur with topical progesterone, this treatment should be seriously considered as an effective and safe alternative clinical therapy for women suffering from menopausal symptoms.

The Latest Scoop on Progesterone is that More is Not Better

George Gillson, M.D., gave two talks, one on insulin and metabolic syndrome (see Issue 5 of the Hopkins Health Watch), and one on the “Hormone Symphony” (Dr. Lee’s original metaphor for the complex interplay of hormones). Dr. Gillson pointed out-along with other speakers at the symposium-that the proper response when natural hormones aren’t working, or are causing side effects, isn’t to raise the dose, but to lower it. I was gratified to hear this emphasized, as it was a point that Dr. Lee was constantly trying to drive home. Both conventional physicians and compounding pharmacists seem to have a tendency towards overdosing with hormones-it’s the old, “if a little is good, more must be better,” approach, which is pretty much guaranteed to backfire when it comes to hormones.

The Stress Connection

Every speaker at this symposium emphasized the role of stress in illness and in hormone imbalances. There’s just no way around it: if you’re constantly stressed it’s going to affect every cell of your body in a negative way, and over time it’s sure to create illness. Poor diet, lack of sleep and not enough exercise are forms of stress on the body, but the most harmful type of stress is the mental/emotional kind caused by rushing around all day, financial worries, relationship issues, and all that goes along with trying to maintain our new millennium zoom zoom lifestyles. There’s a lot to be said for slowing down and simplifying; for introspection and contemplation designed to balance the mind/emotions; and for having a spiritual perspective on life that can help remind us what our real priorities are.

“Used with permission of The Hopkins Health Watch, www.johnleemd.com.”