Now that HRT has been largely discredited, millions of women embarking on the menopause are on the lookout for natural alternatives. One of the favourites is so-called 'natural' progesterone, popularised by the late Dr John Lee. Yet, although the progesterone in progesterone cream is called 'natural' because it is derived from yams, all such progesterone is made in the test tube. Chemists take the sterol diosgenin from yam and manipulate it in the lab, adding extra molecules here and there to approximate what is made by female ovaries.
There are no controls over the amount of progesterone in various brands. Because progesterone cream is sold as a 'cosmetic', it is not subject to strict regulations. Surveys of the most popular brands reveal that these creams can contain anything from no progesterone at all to 700 mg/oz. Indeed, one survey showed that nearly half had 2 mg/oz or less (Townsend Lett Docs, 1996; July: 125-7).
* Absorption is highly individual. Not everyone absorbs progesterone in the same way, and absorption may vary within the body, pooling in just those areas where you've rubbed in the cream (Mauvais-Jarvis P et al. Percutaneous Absorption of Steroids. Academic Press, 1980: 259-65). Even when extraordinarily high doses are used, very little of the hormone actually enters the bloodstream (Lancet, 1999; 354: 1447-8). Although fans of progesterone cream claim that saliva levels, rather than blood tests, yield a more accurate picture of circulating levels of progesterone, high saliva results may be paradoxical and not reflect what is circulating in the body (Maturitas, 2002; 41: 1-6).
* It may not alleviate symptoms. Research shows that progesterone has no effect on vasomotor activity (causing hot flushes), blood levels, bone mineral levels or mood (Menopause, 2003; 10: 13-8). Even high doses of progesterone cream don't increase circulating blood progesterone enough to causes any favourable changes in the endometrium (lining of the womb) (Lancet, 1999; 354: 1447-8).
* It may cause breast cancer. Conventional wisdom also has it that 'natural' progesterone prevents breast cancer. A single study showed that, when women with tumours rubbed on cream, there was a reduction in cell division associated with cancer. However, it included only 40 women and ran for less than two weeks (Fertil Steril, 1995; 63: 785-91). The only other research supporting a protective effect showed that breast cancer survivors taking 50 mg of progestins (medroxyprogesterone acetate) had half the rate of disease reccurrence, contradicting all the evidence from the use of progestogens in HRT showing that progestin actually causes the disease (Lancet, 2004; 363: 453-5).
* Progesterone is a listed carcinogen in many chemical handbooks (IARC Monographs on the Evaluation of Carcinogenic Risk of Chemicals to Humans, December, 1979), and high doses are considered a risk factor for breast cancer (J Clin Endocrinol Metabol, 1983; 57: 82-6). Studies show that women with the highest levels of progesterone have a more than eightfold increased rate of developing the disease (BMJ, 2001; 322: 586-7).
Some proponents, such as Dr David Zava, argue that the effect of progesterone is dose-related, causing breast cancer at low doses, but preventing it at high ones. But even if this were true, no one knows the precise level at which this carcinogen becomes a preventative. Even tried-and-tested hormone treatments like tamoxifen, used in high doses to block oestrogen-sensitive cancers, can cause other cancers, like ovarian cancer.
* There is no evidence that progesterone cream prevents osteoporosis. Dr Lee built his platform on this claim but, as critics point out, Lee's own study was not much more than a hypothesis, based on observation of his patients without proper scientific controls. There is no evidence anywhere that progesterone protects bones (Lancet, 1998; 352: 905-6). In fact, what evidence there is shows that it actually causes the condition (BMJ, 1993; 303: 13-6). One study of women taking the cream found no effect on bone density after an entire year of use (Obstet Gynecol, 1999; 94: 225-8).
What about plant oestrogens?
The other HRT substitutes are soy isoflavones and a number of products derived from plant oestrogens. Phytoestrols are compounds similar to oestrogen, with comparable effects, albeit weaker. The phytoestrogen family includes isoflavones (found mainly in beans such as soybeans, and includes subgroups like genistein), lignans (in seeds, nuts and grains, such as flaxseed) and coumestans (mainly in sprouts). Although these can be ingested as foods, many manufacturers now produce highly concentrated supplements. For example, genistein can be bought over the counter in potent dosages that are virtually equivalent to those in hormone replacement therapy.
* They may not work. Of 11 studies using soy or isoflavone supplements for hot flushes, only three of eight trials lasting more than six weeks showed any signs of improvement (Ann Intern Med, 2002; 137: 805-13), and the longest study showed the same improvement (of 50 per cent) after six months in women given a placebo, suggesting that the effect was probably 'mind over matter'. Other studies of dong quai, evening primrose oil, vitamin E alone, acupuncture, Chinese herbal mixtures or red clover all show no evidence that these can get rid of hot flushes.
* Plant oestrogens may also cause breast cancer. Dr Zava has just completed a study of more than 250 herbal extracts and their ability to bind to hormone receptors in breast tumour cells (Proc Soc Exp Biol Med, 1998; 217: 369-78). Those binding to oestrogen receptors acted as tumour promoters, even at low doses. These included soy, liquorice, red clover, thyme, turmeric, hops and verbena. The highest oestrogen-binding agent was soy isoflavones.
Although research shows that soy and other phytoestrogens protect against cancer, newer studies are weighing in with evidence that concentrated phytoestrogens in pill form are as potent as other types of hormone replacement in causing cancer (Cancer Epidemiol Biol Prev, 1996; 5: 785-94). Even small doses of genistein can promote tumour growth in the breast, causing the authors to caution women with breast cancer not to consume soy (Environ Health Perspect, 1997; 105 [Suppl 3]: 633-6).
Zava and others believe that high doses are needed to suppress the growth of breast and other tumours. But exactly how much is anyone's guess.
As Fredi Kronenberg and Adriane Fugh-Berman wrote in an exhaustive analysis of all natural menopause treatments: 'Supplementing the diet with beans or bean products is a benign intervention. No such presumption of safety can be made for the isolated, often high-dose, isoflavones that are currently sold over the counter' (Ann Intern Med, 2002; 137: 805-13).