Phytotherapy Review & Comment
Alternatives to HRT: The Best Opportunity for Naturopathic Medicine in 2003
by Kerry Bone

On the 9th of July 2002 a press release announced that the National Institutes of Health (NIH) had stopped a major clinical trial investigating the risks and benefits of combined estrogen and progestin in healthy menopausal women. The planned duration of the trial was 8.5 years. After a follow-up at 5.2 years it was decided that the health risks outweighed the benefits. An independent data and safety monitoring board recommended stopping the trial because it found an increased risk of invasive breast cancer (in fact the number of cases of breast cancer had reached a prespecified safety limit).

The study also found increases in coronary heart disease, stroke and pulmonary embolism among study participants receiving the combined estrogen and progestin compared to women receiving placebo. The trial results was published in the Journal of the American Medical Association together with an editorial (JAMA 2002; 288: 321-333, 366-8) and both are freely available from its website (www.jama.com) – go to the Past Issues section, July 17, 2002 link.

Hot on the heels of the estrogen plus progestin trial the National Cancer Institute released the results of a trial studying estrogen alone. The study was also published in JAMA (JAMA 2002; 288: 334-341) but is not freely available from its website. This observational study investigated the association between estrogen-only hormone replacement therapy and ovarian cancer. More than 44,241 postmenopausal women were included in the study which spanned approximately 20 years (1979-1998). The mean age at the start of follow-up was 56.6 years.

Women who used estrogen-only HRT for 10 or more years had a significantly greater risk of developing ovarian cancer than women who did not use HRT. The risk increased with length of estrogen use.

The impact of these studies and the parallel recommendation from various health authorities around the world are still reverberating through our communities. As a phytotherapist I am receiving many more enquiries from patients or potential patients about herbal alternatives for the relief of menopausal symptoms. My experience as a clinician is that herbs can be successfully prescribed in the majority of cases for the alleviation of symptoms such as hot flashes, sweating, mild depression and irritability.

The recommendation now coming through is that HRT is only suitable for short-term treatment in most women. However, it could be argued that this approach to using HRT in fact only briefly delays menopausal symptoms. When the patient stops HRT after 6 or 12 months she will likely experience all the symptoms of estrogen withdrawal once again. There seems to be little point in delaying the inevitable by just 6 or 12 or even 18 months.

In contrast, the aim of herbal therapy is to assist with the adjustment to this important change, particularly to the estrogen withdrawal. It is often the case that herbs will need to be taken for a few years, but eventually the patient will adjust to her new estrogen levels and will be free of symptoms even when the herbs are withdrawn.

Many OTC herbal products are being promoted in the media and there is a particular emphasis now on black cohosh because its efficacy has been supported by clinical trials. But herbalists select from a much wider range of herbs than just black cohosh for menopausal symptoms. In fact, I find many of the other herbs that I recommend in my clinic are much more effective than black cohosh.

In particular, herbs containing steroidal saponins such as in wild yam, Tribulus and false unicorn root are very effective. The compounds in these herbs may exert estrogenic effects by binding with estrogen receptors in the hypothalamus, which are part of the negative feedback mechanism of estrogen control. In the low estrogen environment of peri- and postmenopause, such herbs might alleviate symptoms of estrogen withdrawal through the binding of their steroids to vacant receptors in the hypothalamus. Because some menopausal symptoms are thought to be initiated via the hypothalamus (especially hot flashes), this selective binding could be sufficient to reduce symptoms by convincing the body that more estrogen is present in the bloodstream than there actually is.

Wild Yam
The oral application of wild yam must be clearly differentiated from its use in creams. The use of such creams appears to have arisen from the confusion between the phytochemicals in wild yam and the hormone progesterone. This in turn follows from the fact that yams (Discorea species) are industrially used as a source of progesterone precursors.

Many species of Dioscorea have been cultivated for the industrial manufacture of steroidal hormones. Diosgenin is manufactured from the dioscin in the herb and then undergoes a series of reactions to produce progesterone or hydrocortisone.¹ Despite this well-known industrial process, there is no evidence to suggest that diosgenin is metabolized in the body to produce these steroidal hormones, particularly progesterone. Moreover, diosgenin does not normally occur in untreated wild yam rhizome.

Analysis of saliva samples from women who were using wild yam cream or tablets indicated that their progesterone levels, DHEA levels and total progestin activities were no different from those of untreated women. The women tested were taking products that did not contain added hormones and for the most part the specimens were collected within 12 to 24 hours of product usage assay.²

A trial published in 2001 found a wild yam cream to have little effect on menopausal symptoms. Twenty-three women completed treatment in this randomized, double-blind, placebo-controlled, crossover trial. After a 4-week baseline period, each woman was given active cream and matching placebo for 3 months each. Salivary progesterone levels did not on any occasion exceed the detection limit of the assay.³

Tribulus
One of the best-researched examples of the use of a steroidal-saponin containing herb is Tribulus. Tribulus terrestris leaf is a popular herb in Europe for the treatment of menopausal symptoms. Like wild yam and false unicorn, the leaf of this plant is rich in steroidal saponins.⁴

In an open study, 98% of 50 menopausal women experienced symptom improvement after Tribulus treatment, but not after placebo. Fifty-two percent of patients were experiencing natural menopause and 48% had postoperative symptoms after removal of their ovaries. Predominant symptoms included hot flashes, sweating, insomnia and depression. The dosage prescribed varied, but generally a maintenance dose of 500–750 mg/day of a standardized extract (corresponding to 20 to 30 g of original leaf) was reached after higher initial doses. Treatment did not result in significant changes in FSH, LH, prolactin, estradiol, progesterone and testosterone, although FSH tended to be lower.⁵ There are several other important uses of this wonderful herb which have been supported by clinical research, most notably its effects on both male and female infertility.

Sadly, many Tribulus products on the world market will not be effective for these uses because they are from the wrong plant part (fruit or root instead of leaf) and do not contain the required composition of steroidal saponins.⁶ This is despite what might be claimed on the label in terms of active or marker compounds. Inappropriate methods of analysis have been used and rigorous testing using HPLC will show the absence of protodoiscin and related steroidal saponins in many Tribulus products.

Soy
The value of soy products for treating menopausal symptoms has been questioned, but two recent clinical trials have provided positive evidence. One study examined the change in menopausal symptoms and cardiovascular risk factors in response to 4 months of 100 mg per day of soy isoflavones. The study found a decrease in menopausal symptoms and total cholesterol from soy intake when compared with the placebo group.⁷ In the other study a tofu which was high in isoflavones was compared against placebo for the relief of menopausal symptoms. A statistically significant improvement was observed in 12 of the 15 variables examined. Hot flashes decreased in 76% of treated patients versus 19% of those on the placebo. Significant decreases were also noted for palpitations (77% versus 17%), sleep disturbances (69% versus 16%) and nervousness (56% versus 14%). These results were achieved without any changes in the hormonal profile of patients or in the endometrial thickness.⁸

The safety of soy is controversial. In 2000, two US writers published concerns about the safety of soy in the Townsend Letter.^9,10 Such concerns were also picked up by the media. These issues were adequately countered by Nancy Beckham, who in her published letter in the Townsend Letter wrote: "This article contains incorrect referencing, misrepresentation, misunderstanding, quotes out of context, fractional truths and extreme bias… I have found 43 'misrepresentations' in this particular paper…".¹¹

Other Herbs
Phytotherapists also select other herbs for treating menopausal symptoms such as sage for sweating and St John’s wort for mild depression. The value of St John's wort standardized extract in treating the psychological and vegetative symptoms of menopause was recently assessed in an uncontrolled trial.¹² Substantial improvements in these symptoms were observed and sexual well-being also improved. These results need to be confirmed in a controlled clinical trial.

The use of chaste tree berry (Vitex agnus castus) to treat menopausal symptoms is popular amongst English herbalists.¹³ I have found this herb to be particularly useful for the alleviation of exaggerated PMS symptoms which can occur in the perimenopausal time period.

It should also be stressed that the aim of all herbal treatment is to ensure a comfortable adaptation to the lower levels of female hormones which accompany the climacteric. As such, these treatments are not recommended for indefinite use. Typical treatment times vary from 6 to 18 months, but treatment may be necessary for a few years in some cases.

What is now needed are properly designed clinical trials to objectively investigate the value of the traditional herbal treatments for menopause, particularly the steroidal-saponin-containing herbs. The generation of such evidence will provide a tremendous boost for naturopathic medicine in terms of meeting the need in the community created by the justified demise of HRT as a first line treatment for menopausal symptoms.

References
1. Bruneton J. Pharmacognosy, Phytochemistry, Medicinal Plants. Lavoisier Publishing, Paris, 1995.
2. Dollbaum C. Townsend Letter for Doctors and Patients 1996; 159: 104
3. Komesaroff PA, Black CV, Cable V et al. Climacteric 2001; 4(2): 144-150
4. Stuthe J, Fletcher M, Lambert L, Penman K, Lehmann R, Kitching W, De Voss J. Chemical Constituents of Chamaelirium luteum. Poster presented at 50th Conference Society of Medicinal Plant Research (GA) in Barcelona, Spain. Sept 2002
5. Zarkova S. Tribestan: Experimental and Clinical Investigations. Chemical Pharmaceutical Research Institute, Sofia, Bulgaria.
6. Lehmann R, Halloran K, Ozarko L, Penman K. Poster presented at 50th Conference Society of Medicinal Plant Research (GA) in Barcelona, Spain. Sept 2002
7. Han KK, Soares JM Jr, Haidar MA et al. Obstet Gynecol 2002; 99(3): 389-394
8. Yoles I, Kaplan B, Seidman DS et al. Obstet Gynecol 2002; 99(4 Supp 1): S58
9. Fallon S, Enig M. Townsend Letter for Doctors and Patients 2000; 204: 66-71
10. Fallon S, Enig M. Townsend Letter for Doctors and Patients 2000; 205: 56-58
11. Beckham N. Townsend Letter for Doctors and Patients 2001; 219: 100-103
12. Grube B, Walpart A, Wheatley D. St John's Wort extract: efficacy for menopausal symptoms of psychological origin. Adv Ther 1999, 16(4): 177-186
13. Christie S, Walker AF. Vitex agnus castus. A review of its traditional and modern therapeutic use, current use from a survey of practitioners. Eur J Herb Med 1997/1998; 3(3): 29-45

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