Hormone therapy may increase the risk of breast cancer. Thus, especially the addition of synthetic progestins may play a decisive role according to the results of clinical studies. Overexpression of a special receptor, i.e. the progesterone receptor membrane component-1 (PGRMC1), may offer a potential new pathway to explain the observed increase in breast cancer risk in the combined arm of the Women's Health Initiative. PGRMC1 is expressed in breast cancer tissue and may be important in tumorigenesis. The expression of PGRMC1 in breast cancer tissue is significantly different from that in normal mammary glands. Certain synthetic progestins can increase the proliferation of PGRMC1-overexpressing breast cancer cells and may thus be involved in tumorigenesis, while progesterone and certain synthetic progestins such as nomegestrol or chlormadinone acetate react neutrally. Our investigations point towards an important role of estrogen receptor-α in the signaling cascade, resulting in the proliferative effect induced by progestins. Thus, activation of PGRMC1 may explain the increased breast cancer risk observed during treatment with certain progestins. Very recently, PGRMC1 was investigated in serum samples of lung cancer patients and matched healthy patients; significantly higher concentrations were shown in the cancer patients. Therefore, PGRMC1 might be a predictor for other cancers as well but, according to clinical trials, its importance for a possible screening tool, particularly for breast cancer risk during hormone therapy, seems of interest.

ABSTRACT

Objective This study sought to determine whether postoperative hormone replacement therapy has a negative influence on the progression-free and overall survival of epithelial ovarian carcinoma patients. Methods A retrospective chart review identified 77 patients with invasive epithelial ovarian cancer who had received hormone replacement therapy after primary surgical treatment from January 1995 to December 2010 at Peking Union Medical College Hospital. A 1:1 cohort of patients with the same diagnosis who did not receive hormone replacement therapy were matched by age and stage. An analysis of both progression-free survival and overall survival was performed using Cox proportional hazards models. Results According to the univariate analysis, hormone replacement therapy did not significantly influence progression-free or overall survival. Similarly, different types of hormone replacement therapy (estrogen alone, tibolone alone or an estrogen-tibolone combination) had no significant effect on the prognosis of epithelial ovarian-cancer patients. The FIGO stage, differentiation, histological type and resection status were significantly correlated with progression-free survival, and except for histological type, these factors also significantly influenced overall survival. Finally, the multivariate analysis demonstrated that the strongest independent variable in predicting both progression-free survival and overall survival was the FIGO stage of the disease. Conclusion This study supports the hypothesis that postoperative hormone replacement therapy does not have a negative effect on the progression-free and overall survival of epithelial ovarian cancer patients. However, a multicenter study is needed to support and extend our findings.

Abstract Osteoporosis is responsible for fragility fractures, which are associated with decreased physical and social function. The GINERISK study was a cross-sectional epidemiological study conducted in 4,157 Spanish post menopausal women initially diagnosed with osteoporosis according with WHO criteria within the last two years. The aim of the study was to explore the impact of osteoporosis on health-related quality of life (HRQoL). Menopause-specific and generic HRQoL were assessed, respectively, with the specific Cervantes Scale and the generic SF-12v2 Health Survey. The impact of osteoporosis on HRQoL was ultimately evaluated in 3,328 (80.1%) women who had measurements for both bone mineral densitometry (BMD) and HRQoL. Menopause-specific or generic HRQoL, respectively, was worse in women with current osteoporosis and prior osteoporotic bone fracture (BF) in comparison with current osteoporosis without BF or whose T-score had increased above -2.5 on the BMD after receiving osteoporosis drug therapy. Impaired HRQoL was found both in Spanish post menopausal female populations and the Spanish general female population. Women with osteoporosis with BF had physical and mental summary component scores in the 20(th) and 30(th) percentiles, respectively, of the Spanish general population. Higher risk for cardiovascular death was also associated with greater HRQoL impairment. The use of selective estrogen receptor modulators (SERMs) in women with a BMD T-score ≤ -2.5 was associated with lower impact of osteoporosis on HRQoL, particularly in the domains of physical health and sexuality.

ABSTRACT

Objective To investigate the effect of either genistein, or exercise, or both, on parameters that are indicators of cardiovascular health. Methods We investigated the effect of genistein treatment (300 mg genisten/kg body weight/day), or exercise training, or combined genistein and exercise training, for a period of 6-weeks on physical characteristics, cardiovascular plasma markers, blood pressure, aortic morphology, cardiac structure and oxidative stress in the ovariectomized, OVX Sprague Dawley rat. Comparisons were made to intact rats. Results OVX (compared to intact) resulted in significant decreases in uterine weight (6-fold, P < 0.0001), insulin levels (4-fold, P = 0.0214), insulin/glucose ratio (3-fold, P = 0.0029), and TNF-α plasma levels (2-fold, P < 0.0001). Similarly, aortic blood pressure was significantly increased (by 8%, P < 0.0033) in OVX rats, without changes in aortic luminal or wall dimensions. Heart surface area was significantly increased (by 16%, P = 0.0160) in OVX rats and this was without changes in non-protein thiols levels (a marker of oxidative stress). Physical characteristics were not altered by treatment with genistein, or genistein with exercise, with the exception of increased uterine weight in OVX rats treated under these same conditions. There were no effects of genistein or exercise, on indices of blood pressure and aortic morphology in the OVX rat. However, right ventricular nuclei count was reduced in sedentary genistein-treated rats compared to non-treated control OVX rat. Conclusion Our results indicate that administration of genistein at this dose, treadmill running, or the combination of both, are not associated with any improvement in cardiovascular function and structure, and risk factors in OVX model of postmenopause.

Cutaneous aging is one of the major noticeable menopausal complications that most women want to fight in their quest for an eternally youthful skin appearance. It may contribute to some maladies that occur in aging which, despite not being life-threatening, affect the well-being, psychological state and quality of life of aged women. Skin aging is mainly affected by three factors: chronological aging, decreased levels of estrogen after menopause, and environmental factors. Aged skin is characterized by a decrease in collagen content and skin thickness which result in dry, wrinkled skin that is easily bruised and takes a longer time to heal. Cytokines play a crucial role in the manifestation of these features of old skin. The pro-inflammatory cytokine tumor necrosis factor-alpha inhibits collagen synthesis and enhances collagen degradation by increasing the production of MMP-9. It also lowers the skin immunity and thus increases the risk of cutaneous infections in old age. Deranged levels of several interleukins and interferons also affect the aging process. The high level of CCN1 protein in aged skin gives dermal fibroblasts an 'age-associated secretory phenotype' that causes abnormal homeostasis of skin collagen and leads to the loss of the function and integrity of skin. Further research is required especially to establish the role of cytokines in the treatment of cutaneous aging.

For many years it has been perceived wisdom that hormone replacement therapy for women with a uterus should include a progestin to prevent the proliferative effects of estrogen on the endometrium and endometrial cancer. But, with the reports from the Women's Health Initiative (WHI) and Million Women Study indicating that such regimens are associated with an increased risk of breast cancer, whereas unopposed estrogen may not increase this risk, or even reduce it, it is pertinent to reassess the merits of adding a progestin. In addition, the suggestion from the WHI that the effects of estrogen and progestins are a 'class effect' are clearly inaccurate, as there is particular evidence from the French E3N cohort studies of differential effects of progestins, with progesterone and dydrogesterone additions showing no increase in risk of breast cancer. The data are presented but an answer to the posed question remains unclear and as usual dependent on the circumstances and views of each individual woman and her medical adviser.

ABSTRACT

Interactions between genetic (genome) and environmental factors (epigenome) operate during a person's entire lifespan. The aging process is associated with several cellular and organic functional alterations that, at the end, cause multi-organic cell failure. Epigenetic mechanisms of aging are modifiable by appropriate preventive actions mediated by sirtuins, caloric input, diet components, adipose tissue-related inflammatory reactions, and physical activity. The Mediterranean lifestyle has been for many millennia a daily habit for people in Western civilizations living around the Mediterranean sea who worked intensively and survived with very few seasonal foods. A high adherence to the traditional Mediterranean diet is associated with low mortality (higher longevity) and reduced risk of developing chronic diseases, including cancer, the metabolic syndrome, depression and cardiovascular and neurodegenerative diseases. Reports indicate that some dietary components, such as olive oil, antioxidants, omega-3 and -6 polyunsaturated acids, polyphenols and flavonoids, mediate beneficial anti-aging effects (anti-chronic diseases and increased longevity). Equally, physical activity displays a positive effect, producing caloric consumption and regulation of adipose and pancreatic function. The predictive strength of some food patterns may be a way of developing recommendations for food and health policies. This paper will discuss several ways of improving health during mid-life, focusing on certain groups of functional foods and healthy habits which may reduce or prevent age-related chronic diseases.