Data on optimal hormone formulations routes
Data on optimal hormone formulations, routes of administration, doses and duration of hormone use in young women with POF are lacking (Box 1). Transdermal Bcl Family Set I administration, which avoids the first-pass hepatic circulation and the increase in inflammatory markers such as C-reactive protein, while maintaining beneficial effects on the vascular endothelium, might be more appropriate than oral estrogen therapy for young women with POF.
Of note, the normal premenopausal ovary is an important source of estrogen as well as androgen production. Young women with POF often have lower androgen levels compared with normal ovulatory women . In these young women, testosterone replacement might be important for the development and maintenance of normal muscle mass, the preservation of bone mineral content and normal sexual function . This raises the possibility that the addition of testosterone to the standard cyclical estrogen and progestogen therapy might be necessary for the management of women with POF (Box 1). Although the cardiovascular effects of testosterone therapy in these women are not known, transdermal testosterone has been shown to improve endothelial function in postmenopausal women already receiving standard hormone therapy . A three-year, prospective, double-blind, randomized, placebo-controlled study at the National Institutes of Health is presently being conducted, comparing standard estrogen and progestogen versus estrogen, progestogen and testosterone treatment. The primary outcome parameter is bone mineral density, and secondary outcomes include cardiovascular risk factors, cognition, mood, well-being and sexual function .
Conclusions Women who experience POF are at increased risk for cardiovascular morbidity and mortality 8, 9, 10, 11, 12, 13. Impairment of vascular endothelial function is an early marker of atherosclerosis . POF has been associated with significant endothelial dysfunction, which is restored following six months of cyclical hormone replacement therapy . These findings indicate that the process of atherosclerosis starts early in these women and might contribute to the increased risk of cardiovascular disease. Hormone replacement therapy in young women with POF restores normal physiology and might also have beneficial effects on the cardiovascular system. Further research is required to investigate whether long-term hormone therapy improves prognosis in young women with POF and to assess the effect of different formulations, routes of administration, doses and duration of hormone use in these women.
Introduction Alzheimer’s disease (AD) is a progressive major neurocognitive disorder. It accounts for 60–80% of dementia cases and thus, it is a key determinant of health care costs. Therefore, identifying means for preventing and/or delaying its onset is important ,  Women account for two thirds of AD cases, which has been suggested to be due to, for example, increased life expectancy, or depletion of female sex steroid hormones (estrogen and progesterone mainly) at menopause , . Menopause can be natural (average age 51 years) or induced (anytime between onset of menarche and age of natural menopause); both differ with respect to hormonal senescence which is gradual over years in former and abrupt in latter , . Estrogen is the main hormone of female reproductive system, produced from functional ovaries and has well-established neuroprotective effects as evidenced in basic science and animal studies, though findings from human studies are inconsistent , , . Cell and tissue specific estrogen receptors are distributed throughout human body and brain especially in those areas which relate to AD pathogenesis ,  and same is true for progesterone . These factors promote a plausible association between hormone depletion and higher risk of AD among women. Findings from clinical trials are not supportive of use of hormone therapy (HT) to prevent AD or dementia and consequently a recent Cochrane review concluded that HT is not indicated for preventing dementia or cognitive decline in postmenopausal women . Over 65year old HT users had higher risk of dementia in the Women’s Health Initiative Memory Study (WHIMS) ,  while no significant harmful or beneficial effect was seen with use of menopausal hormone therapy in another study . However, some observational studies suggest that HT is related to decreased risk of AD, if started early after menopause , . Postmenopausal HT use has also been related to adverse outcomes such as cerebrovascular events, cancer, and mortality. Thus, it is important to consider both harms and benefits surrounding HT use , .