Recent concerns surrounding HRT

Abstract

SummaryMillions of women are treated with hormone replacement therapy (HRT) for relief of menopausal symptoms, including vasomotor flushes and sweats for which oestrogen is uniquely and highly effective. Others may continue longer-term treatment in the hope that HRT will help to prevent chronic disease. The preservation of bone mass with continuing oestrogen therapy and reduction of subsequent risk of fracture is well established. Observational studies of the metabolic and vascular effects of oestrogens have suggested a potential benefit in reducing the risk of vascular disease, but recently published randomized controlled trials demonstrate no evidence of benefit in women with established vascular disease or in apparently healthy women. The increased risks of breast cancer and thromboembolic disease have been confirmed in these trials, with evidence of increased risk of stroke. Observational data suggest there may be a small increased risk of ovarian cancer associated with longerterm use of HRT. The premature termination of one arm of the Women's Health Initiative randomized controlled trial caused concern among patients, doctors and pharmaceutical companies. There are difficulties in extrapolating the results from trials using a specific HRT product to advise women on the wide range of other hormone products, doses, combinations and routes of administration. However, in the absence of evidence that other products are safer, the data suggest that for many women the risks associated with long-term use of HRT outweigh the benefits. There are nonhormonal strategies for the prevention and treatment of osteoporosis. HRT is not, and has never been, licensed in the UK for the prevention or treatment of vascular disease, and the data suggesting potential benefit should now be regarded as biased. The absolute incidence of an adverse event is low, and the risk in an individual woman in a single year is very small, but the risks are cumulative over time with long-term use. The risk-benefit balance of each woman needs regular reappraisal with continued use.

Modulation of the firing activity of female dorsal raphe nucleus serotonergic neurons by neuroactive steroids

“…Even if a clear link has not yet been firmly established, recent reports have suggested that hormonal replacement therapy (HRT) could induce undesirable side effects (see review by Armitage et al 2003), which has led many patients to stop their HRT treatments. Natural hormones might, therefore, not be the best candidates as long-term adjuvants for antidepressant treatments, which would have to be administered presumably for several years to patients suffering from refractory depression.…”

Expression of an estrogen receptor agonist in differentiating osteoblast cultures

“…An important role for 17␤E in various aspects of skeletal growth and integrity is well known, and replacement therapy with native or synthetic ER modulators has historically been a potent adjunct to maintain bone mass and prevent fractures in postmenopausal women. Increased incidence of metabolic disease with certain ER modulators in nonskeletal tissues instills valid concerns, however, and may limit the use of some of these agents (34,35). ER modulators have complex direct and indirect effects on gene expression that can differ in part from 17␤E and often appear tissue restricted (6,36).…”

Genistein, a Phytoestrogen, Attenuates Monocrotaline-Induced Pulmonary Hypertension

“…Contrary to genistein, an increase in the risk of breast cancer by estrogen treatment has been considered despite its protective effect on cardiovascular disease [29]. In addition, genistein is known to inhibit tyrosine kinase and has been reported to suppress proliferation of vascular smooth muscle cell(s) in an experimental model of hypertension [30,31,32].…”