Wild Yam and Progesterone Creams
By Adriane Fugh-Berman, MD, and Anthony R. Scialli, MD
Topical transdermal progesterone and wild yam creams have been promoted for treating osteoporosis, hot flashes, and PMS, as well as for preventing breast cancer. Additionally, some alternative medicine practitioners recommend transdermal progesterone creams as the progestin component of hormone replacement therapy, often in conjunction with estriol or tri-estrogen (estrone, estradiol, and estriol, typically in a 1:1:8 ratio). "Natural" (micronized) progesterone is derived from diosgenin in soybeans (Glycine max) or an inedible Mexican wild yam (Diascorea villosa).
Hot Flashes
Progesterone decreases vasomotor symptoms, and topical progesterone cream (20 mg progesterone/d) reduced hot flashes in a study of 102 healthy postmenopausal women with a primary endpoint of bone mineral density.1 There was no effect on bone (see Alternative Therapies in Women’s Health, April 1999).
Diosgenin is not converted to progesterone in the human body, so oral or topical wild yam preparations would be expected to be ineffective for hormonal purposes. There is a question among herbalists of whether wild yam has estrogenic effects, but a recent double-blind, placebo-controlled crossover trial that tested wild yam cream against placebo for three months in 23 symptomatic menopausal women found no benefit for wild yam in reducing hot flashes or night sweats (both improved slightly in both groups).2 Additionally, there were no changes from baseline in body weight, blood pressure, serum estradiol levels, serum or salivary progesterone, total cholesterol, triglyceride, HDL, follicle-stimulating hormone, or glucose.
Progesterone Cream Bioavailability
A favored theory of progesterone cream proponents is that high salivary levels reflect bioavailable hormone better than serum levels, and that erythrocytes transport progesterone to target tissues.3 Both of these theories have been discredited by recent studies.
Although endogenous salivary progesterone levels appear to be related to serum levels, with serum free progesterone levels five-fold those found in saliva,4 this relationship apparently does not hold with exogenous application. A randomized, double-blind, placebo- controlled, three-armed trial in 24 postmenopausal women found that topical progesterone cream (up to 80 mg/d) caused very high and variable progesterone levels that were unrelated to plasma levels.5 Another study showed that salivary, but not serum, progesterone levels rose after a single 64 mg progesterone cream application.6
The Lewis study is the only one to compare serum, salivary, and red blood cell levels; although daily doses of progesterone approximated daily peak luteal phase production, neither absorption nor excretion of progesterone approached luteal phase levels, and while plasma progesterone levels were low, erythrocyte progesterone levels were even lower. O’Leary has pointed out that the theory that progesterone is taken up by erythrocytes goes against data showing that progesterone distributes equally between a phosphate buffer dialysate and red blood cell membranes.
High salivary progesterone levels in conjunction with low serum levels were noted in the O’Leary and Lewis studies; both investigators note the possibility of lymphatic transmission of progesterone into saliva. Lewis conducted an experiment that excluded spurious entry of progesterone into saliva; results were not affected. In an effort to determine whether conversion of progesterone to 5 a-reduced progestins could contribute to low systemic progesterone levels, one investigator ingested a 5 a-reductase inhibitor (finasteride, 5 mg daily ´ 9 days), but this enzyme inhibitor did not affect results.
Although studies are consistent in showing that topical progesterone cream is absorbed, even high doses result in serum progesterone levels that are only about a third of those achieved by oral ingestion (Click here to see Table 3). This amount of progesterone absorption is insufficient to prevent estrogenic stimulation of the endometrium. In fact, the one study that looked at endometrial effects found no evidence of a secretory endometrium after application of transdermal progesterone cream up to 64 mg/d for 14 days.
Conclusion
Transdermal progesterone should not be used as the progestin component of hormone replacement therapy, and does not preserve bone. There is limited evidence that transdermal progesterone, but not wild yam cream, may be helpful in treating hot flashes. Salivary measurements of progesterone do not reflect serum levels and should not be trusted. The use of progesterone creams should be discouraged or should be used only in conjunction with the topical application of snake oil.
References
1. Leonetti HB, et al. Transdermal progesterone cream for vasomotor symptoms and postmenopausal bone loss. Obstet Gynecol 1999;94:225-228.
2. Komesaroff PA, et al. Effects of wild yam extract on menopausal symptoms, lipids and sex hormones in healthy menopausal women. Climacteric 2001;4: 144-150.
3. Lee JR. Use of Pro-Gest cream in postmenopausal women. Lancet 1998;352:905.
4. Wang DY, Knyba RE. Salivary progesterone: Relation to total and non-protein-bound blood levels. J Steroid Biochem 1985;23:975-979.
5. Lewis JG, et al. Caution on the use of saliva measurements to monitor absorption of progesterone from transdermal creams in postmenopausal women. Maturitas 2002;41:1-6.
6. O’Leary PO, et al. Salivary, but not serum or urinary levels of progesterone are elevated after topical application of progesterone cream to pre- and postmenopausal women. Clin Endocrinol 2000;53:615-620.
7. Carey BJ, et al. A study to evaluate serum and urinary hormone levels following short and long term administration of two regimens of progesterone cream in postmenopausal women. BJOG 2000;107:722-726.
8. Burry KA, et al. Percutaneous absorption of progesterone in postmenopausal women treated with transdermal estrogen. Am J Obstet Gynecol 1999;180(6 Pt 1):1504-1511.
9. Cooper A, et al. Systemic absorption of progesterone from Progest cream in postmenopausal women [research letter]. Lancet 1998;351:1255-1256.
10. Wren B.G, et al. Micronised transdermal progesterone and endometrial response. Lancet 1999;354:1447-1448.
Fugh-Berman A, Scialli AR. Wild yam and progesterone creams. Altern Ther Women's Health 2002;4:54-56.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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