br Pathophysiology of premature ovarian
Pathophysiology of premature ovarian failure By the age of 40 years, 1% of women spontaneously develop POF . The normal menopause occurs at an average age of 51 years  and results from ovarian follicle depletion , whereas POF is a heterogeneous disorder and can result from either follicle dysfunction or follicle depletion . Indeed, a wide spectrum of pathogenic mechanisms can lead to POF, including chromosomal, genetic, autoimmune, metabolic and iatrogenic causes (Table 1). The incidence of familial cases varies from 4–30% in several studies . In most cases, no etiology of ovarian failure can be identified, hence the use of the term ‘karyotypically normal spontaneous POF’. At one time, POF was considered to be irreversible and was described as ‘premature menopause’. POF is not an early natural menopause; these women produce 7ACC2 intermittently and might ovulate, despite the presence of high gonadotropin concentrations . Pregnancies have occurred in 5–10% of women after the diagnosis of POF, even in women with no follicles on ovarian biopsy . POF is defined by the presence of at least four months of amenorrhea and two or three serum follicle-stimulating hormone values greater than 40IU/l (obtained at least one month apart) in women younger than 40 years of age . The main presenting complaint in these women is the cessation of menses. POF can present as either primary amenorrhea (absence of menses in a girl who has reached the age of 16 years) or secondary amenorrhea (cessation of menses in a woman previously menstruating for six months or more). Primary amenorrhea is not associated with vasomotor symptoms of estrogen withdrawal. Women who experience secondary amenorrhea commonly report hot flashes, night sweats, atrophic vaginitis, dyspareunia, fatigue and mood changes. In general, these women have normal fertility before the disorder develops. The clinically indicated ‘workup’ should include tests for the diagnosis of possible associated autoimmune disorders such as hypothyroidism, diabetes mellitus and Addison\'s disease , whereas ovarian biopsy and anti-ovarian antibody testing have no proven clinical benefit in POF . Baseline bone mineral density testing should be performed in all women with POF but mammography should be performed annually only after the age of 40 years according to standard guidelines. Early loss of sex steroids in women with POF has been associated with a twofold increase in age-specific all-cause and cardiovascular mortality . Women with POF should be treated with hormone replacement therapy to compensate for the decreased ovarian production of sex steroids. Furthermore, they should be monitored annually for their compliance and response to treatment.
Evaluation of endothelial function in the assessment of cardiovascular function Endothelial dysfunction is considered to be the first step in the process of atherosclerosis . The endothelium, the innermost layer of cells in the vascular wall, is an important regulator of vascular homeostasis, maintaining the balance between vasodilation and vasoconstriction; inhibition and stimulation of smooth muscle cell proliferation and migration; and thrombogenesis and fibrinolysis. The endothelium regulates vascular tone through the release of vasodilators, such as nitric oxide (NO), prostacyclin and bradykinin, and vasoconstrictors, such as endothelin and angiotensin II, in response to physical and chemical stimuli. NO mediates many vasoprotective effects of the endothelium; apart from being the most potent vasodilator, NO also inhibits leukocyte adhesion and infiltration, low-density lipoprotein (LDL) oxidation, vascular smooth muscle cell proliferation, and platelet adherence and aggregation . Reduced NO bioavailability, because of reduced production and/or increased inactivation of NO by reactive oxygen species, disturbs the balance between vasoconstrictors and vasodilators, and endothelial dysfunction occurs, initiating a series of processes that promote atherosclerosis.