Quality of life in climacteric women.

Health-related quality of life (HRQoL) refers to the effects of an individual's physical state on all aspects of psychosocial functioning. For postmenopausal women, HRQoL is the only global criterion that is decisive for their daily well-being. Symptoms experienced during menopause and sociodemographic characteristics affect quality of life in postmenopausal women. In younger, symptomatic, postmenopausal women, HRQoL may be significantly diminished. However, quality of life after menopause is influenced by many additional, non-menopausal factors. In the last decades, more specific symptom lists or other questionnaires have been developed. Such scales would qualify as standardized or disease-specific by fulfilling four criteria: (1) they have been constructed on the basis of a factor analysis; (2) they consist of several subscales, each measuring a different aspect of a specific symptomatology; (3) the scales possess sound psychometric properties; and (4) they have been standardized using adequate populations of women. A variety of instruments currently dominating international practice are here reviewed. Therapeutic approaches that treat climacteric symptoms and all measures ameliorating unfavorable non-hormonal factors could improve HRQoL among postmenopausal women. This includes partnership and sexual counseling as well as psychosocial measures. Menopausal hormone therapy (MHT) may reverse this deterioration of HRQoL if it is due to postmenopausal estrogen deficiency. On the contrary, when MHT is prescribed to asymptomatic younger and older postmenopausal women, no gain in HRQoL can be obtained.

Progesterone--promoter or inhibitor of breast cancer.

Based on the results of a French cohort of postmenopausal women, it has been claimed that micronized progesterone does not enhance breast cancer risk. The impact of reproductive factors on breast cancer risk and a high prevalence of occult breast carcinomas at the time of menopause suggest an involvement of endogenous progesterone in the development of breast cancer. High mammographic density in the luteal phase and during treatment with estrogen/progestogen combinations reflect a change in the composition of mammary stroma and an increased water accumulation in the extracellular matrix which is caused by hygroscopic hyaluronan-proteoglycan aggregates. Proteoglycans are also involved in the regulation of proliferation, migration, and differentiation of epithelial cells and angiogenesis, and may influence malignant transformation of breast cells and progression of tumors. Reports on a lack of effect of estrogen/progesterone therapy on breast cancer risk may be rooted in a selective prescription to overweight women and/or to the very low progesterone serum levels after oral administration owing to a strong inactivation rate. The contradictory results concerning the proliferative effect of progesterone may be associated with a different local metabolism in normal compared to malignant breast tissue. Similar to other progestogens, hormone replacement therapy with progesterone seems to promote the development of breast cancer, provided that the progesterone serum levels have reached the threshold for endometrial protection.

Assessment of health-related quality of life in menopause and aging.

There is a great need for the accurate assessment of health-related quality of life (HRQOL) in clinical practice, research, health interventions and health planning. The menopause transition and special issues influencing the health of women as they age can affect quality of life. The assessment of these effects requires a variety of validated instruments to capture their influence in a variety of populations and for a variety of outcomes. This review identifies the important measurement properties of HRQOL instruments, determinants of health status and the currently available measures of HRQOL. Specifically, the reliability, validity and applicability of HRQOL instruments designed for use at the climacteric are individually discussed. It is important to choose validated and appropriate instruments depending on the individual or population being assessed and the relevant HRQOL issues.

Hormones and progeny of breast tumor cells.

The rudimentary human glandular breast, with the approach of puberty, starts to grow both at glandular and stromal sites. Full differentiation is a gradual process and takes many years, and is only fully attained by pregnancy. The risk of breast cancer is inversely related to parity. Women during adolescence have the highest susceptibility to breast cancer development. This appears to be the period when the mammary gland has the highest number of stem cells. Stem cells may represent important targets for transformational events. Immunohistochemistry allows for identification of the lineage-specific precursor glandular and myoepithelial cells and their differentiated progeny. Both estrogen receptor subtypes are found in epithelial cells of alveoli and ducts as well as in stromal cells. Immunophenotypia of benign proliferative breast disease favors a fundamentally different epithelial composition from that of most malignant epithelial proliferations such as atypical ductal hyperplasia, ductal carcinoma in situ, lobular neoplasia and invasive breast carcinoma. Immunophenotypical characterization of these lesions assists in distinguishing benign from malignant disease. Based on the observation of bilateral risks and frequent multifocality with atypical ductal hyperplasia, atypical lobular hyperplasia and lobular carcinoma in situ, it is suggested that these may represent risk factors as well as precursors. One should, however, realize that ductal as well as lobular premalignant breast lesions ultimately arise from stem cells in the terminal duct lobular units. Estrogen receptor-beta (ERbeta)-positive and ERalpha-negative expression characterizes the highest levels of proliferative cancer cell activity. Point mutations and alterations of co-activators and co-repressors will also determine hormone sensitivity. There is evidence for different genetic pathways in the development of ductal carcinoma in situ and lobular carcinoma in situ. While they share recurrent 16q losses, a second hit in the E-cadherin gene explains the advent of lobular lesions and their common existence with the primary ductal type. Based on our immunocytochemical observations, the most likely target cell of malignant transformation is the Ck18/18-positive and ER-negative transient cell of normal breast epithelium. Pregnancy confers a different genomic imprint to breast epithelial stem cells. Further elucidation of this mechanism may assist in developing appropriate means of breast cancer prevention. This paper is the Pieter van Keep Memorial Lecture given by Professor Hermann Schneider at the 11th World Congress on the Menopause, October 18-22, 2005, in Buenos Aires, Argentina.

The World Veterinary Association and animal welfare.

The World Veterinary Association, as the global representative of the veterinary profession, recognises the global influences on animal welfare and the changing role of the veterinarian in response to the changing attitudes of the human population. While urban populations are now dictating animal welfare standards, many practices still have a cultural and even religious basis. Veterinarians recognise these influences, but base their recommendations for animal welfare on scientifically justified practices. Veterinarians work not only for urban clients with their companion animals, but also very importantly with rural clients who provide the source of animal-based foodstuffs and goods sought by an increasingly demanding human population. The controversial areas of intensive animal production and the transportation that is required to move large numbers of animals around the world require veterinary supervision to ensure that animal welfare is preserved. The development of animal welfare standards is an ongoing process, with the major international effort being led by the World Organisation for Animal Health.

IARC monographs program on carcinogenicity of combined hormonal contraceptives and menopausal therapy.

The World Health Organization International Agency for Research and Cancer (IARC), in June 2005, has classified combination hormone contraception and menopausal therapy as carcinogenic in humans. The IARC's distinction is to identify potential carcinogens associated with nutrition, environment and pharmaceutical products. They do not produce risk-benefit analyses for any country or population. Their conclusions are highly controversial in that no proof is presented for a causal relation of estrogens with reproductive cancer, be it plausibility according to mechanisms of action or experimental evidence in the animal model. Equating natural compounds like estradiol with defined carcinogens like asbestos, tobacco smoke as well as indispensable drugs such as aspirin and tamoxifen is of no substantial clinical relevance. Thus, there are no new reasons to change current management principles with combination hormone contraception and therapy.

Pulsed estrogen exposure selectively modulates tissue response: a hypothesis.

All postmenopausal hormone replacement therapies (HTs) aim to provide a steady mid-follicular serum concentration of estrogen, with the exception of pulsed estrogen therapy, which concentrates hormone exposure in the few hours following administration. This alteration in the kinetics of estradiol exposure does not change the beneficial effect of HT on climacteric symptoms or bone loss, but does reduce the stimulation of the breast and uterus leading to less mastalgia and bleeding. The following hypothesis provides a plausible pharmacological explanation as to how estradiol kinetics can selectively modify tissue response. Pulsed estradiol exposure influences the relative abundance of estrogen receptors (ERs) alpha and beta, via a tissue-dependent non-genomic signaling pathway, resulting in selective upregulation and activation of ERbeta in breast and endometrium, but not in bone. In addition, pulsed estrogen exposure also increases local concentration of 2-methoxyestradiol, a specific estradiol metabolite with proven anti-tumor properties.

Androgens and antiandrogens.

The role of androgens in women's health has been generally neglected. Currently available assays are lacking in sensitivity and reliability at the lower ranges. Circulating androgens as prohormones for other steroids (e.g., androgens) have an ubiquitous role on diverse physiological and behavioral systems. Clinical assessment of both androgen production and androgen availability can be achieved by measurement of two or three essential values. These include either total T and sex-hormone binding globulin (SHBG), free T and SHBG, or free T and total T. The free testosterone index (total T/SHBG) correlates well with free or bioavailable T and can be used as a substitute. DHEA-S is the most useful measure of adrenal androgen production in women. Androgen insufficiency in women is not a specific consequence of natural menopause, but may occur secondarily to the age-related decline in both adrenal and ovarian androgen production. Since estrogen effects are also strongly linked to mood, psychological well-being, and sexual function in women, the diagnosis of androgen insufficiency should only be made in women who are adequately estrogenized. Before initiating a trial of androgen replacement therapy, a comprehensive clinical assessment should be performed in all cases. Approved androgen replacement therapy is not yet available in most countries for treatment of female sexual dysfunction. This would include T supplements or DHEA. Several new progestins have been synthesized in the last decade. Dienogest is a hybrid progestin that is derived from both the pregnane and the estrane groups with a 17alpha-cyanomethyl radical; drospirenone is derived from spirolactone. Somehow, the molecules available have demonstrated antiandrogenic properties. Cyproterone acetate (CPA) is the most potent antiandrogenic progestin, followed by dienogest, drosperinone, and chlormadinone acetate. Nomegestrol acetate and medrogestone also exert some antiandrogenic properties and are similar to chlormadinone acetate in antiandrogenic potency. While androgens act positively on libido in women, antiandrogenic properties in doses used in HRT do not appear to have a negative effect. Progestins used in HRT have varying pharmacological properties that are associated with different adverse effects. The new progestins with antiandrogenic properties avoid many of the androgenic side effects related to testosterone-derived progestins. They also have the potential of not counteracting beneficial estrogen effects, for example, on the cardiovascular system or mental tone.

Hormone therapy: the European women's perspective.

OBJECTIVES: To identify and describe the knowledge and attitudes of European women towards hormone therapy (HT) and to determine the key data of HT use in Europe. METHODS: A total of 8012 women aged 45-75 years were interviewed via standardized computer-aided telephone interviewing. The main outcome measures were history of HT use, opinions and knowledge of HT, reasons for HT use or for the rejection of it. RESULTS: A total of 73% of all interviewed women were aware of HT as a treatment option for menopausal symptoms; 16% were currently using HT, 16% were former users and 68% of respondents had never used an HT product. The most frequently mentioned benefit of HT was relief of hot flushes (22%), followed by improvement of general well-being and quality of life (17%) and prevention of osteoporosis (16%). Cancer, and particularly breast cancer, was considered as a major risk of HT by 35% of the women. Ranking second in risks was weight gain (10%), followed by thrombosis or blood clots (7%). CONCLUSIONS: The findings of this survey demonstrate the preponderant differences in awareness of benefits and risks in HT users. To a large extent, users are satisfied with their HT and willing to pursue its use for longer periods of time.

[Reliability of the Menopause Rating Scale (MRS): Investigation in the German population]. / Reliabilität der Menopause-Rating-Skala (MRS) - Untersuchung für die deutsche Bevölkerung.

The Menopause Rating Scale (MRS) is a well accepted instrument to measure the severity of menopausal symptoms. As yet, however, investigations had not specifically been directed towards short-term test-retest reliability of the scale. The MRS was twice applied in a random sample of 45-65 years aged women of the German Cohort Study of Women's Health with a distance between the measurements of 14 days. The response rate in the sample was 70 %. The correlation coefficient (Pearson) of the sum-score of the two measurements was r = 0.82. The high repeatability of the test results confirms our clinical experience and emphasizes excellent practical applicability. The MRS can be recommended for the clinical practice as a reliable scale both for the measurement and long-term surveillance of menopausal complaint dynamics.