Dr. Antoinette M. Lee (Ph.D.)
Department of Psychiatry The University of Hong Kong, Hong Kong

The climacteric represents an important stage of a woman's life. Hormonal changes interact with a variety of psychosocial events make this phase a potentially distressing period not only for menopausal women but also for their significant others. Much of the research on menopause is conducted in the West. Although Chinese women make up one-fourth of the world's female population, little is known of their menopausal experiences. The common wisdom is that menopausal symptoms are either absent or have limited impact on Chinese women. The present study documented the existence and severity of menopausal complaints among Chinese women. Indeed, it was found that 63.8% of perimenopausal and 50.7% of postmenopausal women experience 10 or more symptoms, and 25.5% of perimenopausal and 2 1.1% of postmenopausal women experience 20 or more symptoms. The latter group of women may very well need help and benefit from treatment.

The study also highlighted that in addition to vasomotor and other somatic symptoms, emotional, cognitive, and sexual complaints are also common. In this regard, the psychosexual dimensions of menopause should not be neglected. Treatment that encompasses the whole spectrum of menopausal complaints is much needed in the quest for providing quality care for perimenopausal and postmenopausal women. Addressing the psychosexual aspects of menopause will help in alleviating the suffering of both menopausal women and their significant others, and improve their quality of life.

Victor W. Henderson, MD, MS
Departments of Geriatrics, Neurology, and Pharmacology & Toxicology; Donald W. Reynolds Center on Aging, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA

Estrogen has a number of genomic and nongenomic actions that affect brain processes relevant to long-term memory and to dementia caused by Alzheimer's disease. These effects include modulation of the cholinergic system (acetylcholine is a neurotransmitter important to memory), enhancement of long-term potentiation (a physiological process thought to be involved in memory formation), growth of new neurons within the hippocampus, and reduced production of beta-amyloid (an abnormal protein found in Alzheimer brain). However, evidence from human studies to support or refute a clinically important role for estrogen is sparse. This is particularly so for data derived from randomized, placebo-controlled, double-blind trials of estrogen in postmenopausal women. Results of short-term clinical trials suggest that estrogen helps preserve long-term memory in women with the abrupt loss of ovarian function. There are almost no long-term clinical trial data on preventing age-associated memory loss despite a pressing need for valid data from such trials. With respect to dementia, observational data indicate an association between estrogen therapy after the menopause and a lower risk of developing Alzheimer's disease. Randomized controlled trials are underway to examine this reported association. For women who already show symptoms of Alzheimer's disease, results from three recent randomized controlled trials failed to demonstrate convincing effects of estrogen monotherapy on cognitive abilities or overall function. The possibility that estrogen might augment effects of cholinergic therapy in Alzheimer's disease remains to be evaluated in randomized clinical trials. Few clinical studies have yet examined effects of tissue selective estrogenic compounds on memory or dementia.

Susan R Davis MD PhD
The Jean Hailes Foundation, Clayton, Vic Australia

Sex steroids influence mood, well-being and libido. In addition both estradiol and testosterone modify vascular function such that insufficiency of either or both may potentially have unfavorable effects on pelvic blood flow and sexual function. Estrogen levels fall precipitously at menopause where as testosterone levels appear to decline gradually with age from the mid reproductive years. Complete post menopausal hormone therapy should be seen as estrogen with consideration of the need for testosterone for all women, plus progestin for endometrial protection as indicated.

A new generation of hormone therapy options have become available, thus increasing the choices for postmenopausal women. Tibolone is a compound that can be selectively metabolized by individual tissues to its oestrogenic, progestogenic or androgenic metabolites and thus exhibits tissue specific hormonal effects. Tibolone alleviates climacteric vasomotor symptoms and displays a dominant progestogenic effect on the endometrium. Tibolone also appears to improve mood and libido with potential mechanisms including lowering of SHBG and increased bioavailable endogenous sex steroids, increased ßendorphins and direct steroid receptor effects of its various metabolites. As women increasingly present in their postmenopausal years with the problem of diminished libido viable treatment options need to be available. Tibolone is a therapeutic alternative that will suit many women.

Dr. FA Helmond, PhD
Organon International, Oss, The Netherlands

Tibolone is a unique tissue-specific compound with positive effects on climacteric symptoms and bone without stimulating endometrium and breast tissue. After oral administration tibolone is rapidly converted by the enzymes 3_/ß-hydroxysteroid-dehydrogenases into 3_ and 3ß-OH metabolites. These hydroxyl-metabolites bind specifically to the alpha isomer of the estrogen receptor. Another important metabolite is the Δ4-isomer of tibolone which can be formed in the endometrial tissue by the enzyme 3ß-hydroxysteroid dehydrogenase-isomerase. This metabolite has strong binding capacities to the progesterone and androgen receptor but not to the estrogen receptor. The estrouenic activity of tibolone on the central nervous system has been demonstrated in a number of studies showing a reduction of the number of hot flushes and sweats and positive effects on mood, libido and sexual function. Tibolone prevents bone loss in estrogen-deficient conditions and the mode of action of tibolone appears to be via the estrogen receptor. Tibolone maintains bone mineral density in a similar way as estrogens and markers for bone resorption and formation all decrease pointing to a decreased bone turnover similar to estrogens. It has been found that tibolone and its Δ4-isomer have a strong progestogenic effect on human endometrial fragments. A low incidence of endometrial proliferation and hyperplasia has been demonstrated in endometrium biopsies collected in clinical trials further establishing tibolone's safety on the endometrium. The incidence of vaginal bleeding is in general low with tibolone and during the first 3-6 months even significantly less compared to continuous combined preparations. It has also been shown that tibolone does not increase mammographic density and has a lower incidence of breast pain in comparison to conventional HRT. This is most likely the result of the inhibition of tibolone and its metabolites of the enzyme sulfatase. In conclusion: Tibolone is a unique tissue-specific compound with positive effects on climacteric symptoms and bone without stimulating endometrium and breast tissue.