Hormone replacement therapy in menopausal women: Past problems and future possibilities.

Oral administration of conjugated equine estrogens (CEE) with and without the synthetic progestin medroxyprogesterone acetate (MPA) in postmenopausal women is associated with side-effects that include increased risk of stroke and breast cancer. The current evidence that transdermal administration of estradiol may provide a safer alternative to orally administered CEE is reviewed. Transdermally administered estradiol has been shown to be an efficacious treatment for hot flushes possibly without the increase in blood clotting that is associated with administration of oral CEE. Further, natural progesterone may have a more beneficial spectrum of physiological effects than synthetic progestins. The substantial differences between CEE compared with estradiol and estriol, as well as the differences between synthetic MPA and natural progesterone, are detailed. Estriol is an increasingly popular alternative hormone therapy used for menopausal symptoms. There is evidence that estriol, by binding preferentially to estrogen receptor-beta, may inhibit some of the unwanted effects of estradiol. New clinical trials are needed to evaluate the safety and efficacy of topically or transdermally administered combinations of estradiol, estriol and progesterone. Future studies should focus on relatively young women who begin estrogen supplement use near the start of menopause.

Is bio-identical hormone replacement therapy safer than traditional hormone replacement therapy?: a critical appraisal of cardiovascular risks in menopausal women.

Recent clinical trials have demonstrated an increase in the risk of cardiovascular disease (CVD) in women using oral hormone replacement therapy (HRT). Bio-identical HRT (BHRT) is widely used by alternative healthcare practitioners for the treatment of symptoms of menopause, with the prevailing assumption that BHRT provides the benefits of HRT while attenuating the risks. However, considering the serious risks of HRT, the use of any form of HRT, including BHRT, without sufficient scientific evaluation may create considerable risk.The main hormone found in BHRT is estriol. Estriol is used alone or in combination with estradiol and estrone. The total daily oral dose of BHRT used is, on average, ten times higher than that used in HRT, and both oral and topical forms are used for bio-identical hormone administration. The clinical trials that have examined cardiovascular outcomes associated with estriol therapy are limited, and there is evidence to demonstrate variable effects on markers associated with cardiovascular risk.Based on the current evidence, the same cardiovascular risks that have recently been found to be associated with oral HRT may also be associated with the administration of oral estriol in BHRT. The use of oral bio-identical hormones cannot be promoted until further evidence is available to demonstrate its safety.

The potential of 5-hydryoxytryptophan for hot flash reduction: a hypothesis.

Hormone replacement therapy (HRT) is contraindicated in women with a history of breast cancer or a high risk of breast cancer development. Recent results from large clinical trials, such as the Women's Health Initiative, have demonstrated increased risks of thromboembolic events and a moderate increased risk of breast cancer in women using conjugated estrogens and progestogens. There is a need for viable non-hormonal alternative treatments to HRT, such as nutritional and botanical therapies, in this population of women, who tend to experience more significant vasomotor symptoms. Safe and effective therapies that do not stimulate breast cell proliferation could prove extremely useful for the management of such symptoms for women in both low- and high-risk breast cancer populations. As a non-hormonal treatment, anti-depressants, such as selective serotonin reuptake inhibitors (SSRIs), have been shown to improve hot flash symptoms in women. The proposed mechanism is related to an increase in serotonin allowing for an increase in the set point of the brain's thermoregulator. In small clinical studies, the administration of tryptophan and 5-hydroxytryptophan (5HTP), the precursors of serotonin, have been shown to reduce depressive symptoms, possibly by enhancing the synthesis of serotonin. Thus, increased serotonin levels may have the ability to decrease hot flashes in a mechanism similar to that of SSRIs without the risks of breast cell stimulation. This would be particularly desirable for menopausal women with breast cancer or with risks of breast cancer. This article discusses the background information on hot flashes, SSRIs, tryptophan, and 5HTP, and possible clinical application of 5HTP for menopausal women with breast cancer risk.

A pilot study to examine a combination botanical for the treatment of menopausal symptoms.

OBJECTIVE: Hormone replacement therapy has become a controversial treatment for symptoms of menopause, leading many women and their physicians to search for safer, effective alternatives. Certain botanicals are known to contain phytoestrogenic activity, which may be helpful in alleviating menopausal symptoms. We report the results of a study using a combination botanical supplement to treat menopausal symptoms. DESIGN: Prospective pilot study. SETTING/LOCATION: Family practice medical center, Phoenix metropolitan area. SUBJECTS: Eight (8) women with moderate vasomotor and somatic symptoms of menopause. INTERVENTION: Combination botanicals daily for 3 months. OUTCOME MEASURES: Modified Kupperman Index (KI), daily hot flashes severity, and overall quality of life (QoL) using the SF-36 index, which were collected at enrollment, during treatment, and at the end of treatment. RESULTS: Mean KI total symptoms decreased from 30.3 +/- 7.5 to 22.9 +/- 8.4 (95% CI, 25-34), p = 0.0028. Daily hot flashes decreased from 68.1 +/- 14.3 to 39.6 +/- 9.7 (95% CI, 38-46), p = 0.0003, and the overall QoL also improved at the end of treatment. CONCLUSIONS: This pilot study demonstrates the potential benefit of a combination botanical for improving moderate menopausal symptoms in women. The efficacy and role of combination botanicals for long-term use to reduce menopausal symptoms requires further exploration.