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Menopause

Menopause is a process of permanent cessation of menstruation at an end of reproductive life that is cause by loss of ovarian follicular activity. It is when the last and final menstruation occurs. Clinical diagnosis can be confirmed after following stoppage of menstruation (amenorrhea) for 12 consecutive months with no other pathology. This is the time a woman is declared to reach menopause only retrospectively. Premenopause refers to the period prior to menopause, postmenopause to the period after menopause and perimenopause to the period around menopause (40–55 years).

Climacteric is the period of time during which a woman passes from the reproductive to the nonreproductive stage. This phase covers 5–10 years on either side of menopause.

Perimenopause is the part of the climacteric when the menstrual cycle is likely to be irregular.

Postmenopause is the phase of life that comes after the menopause.

Age at which menopause occurs is genetically predetermined. The age of menopause is not related to age of menarche or age at last pregnancy. It is also not related to number of pregnancy, lactation, use of oral pill, socioeconomic condition, race, height or weight. Thinner women have early menopause. However, cigarette smoking and severe malnutrition may cause early menopause. Age of menopause ranges around 45–55 years, average about fifty years.

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Few years prior to menopause, along with depletion of the ovarian follicles, the follicles become resistant to pituitary gonadotropins. As a result, effective folliculogenesis is impaired with diminished estradiol production. There will be a significant reduce with the level of serum estradiol from 50–300 pg/mL before menopause to 10–20 pg/mL after menopause. This decreases the negative feedback effect on hypothalamopituitary axis resulting in increase in FSH. The increase in FSH is also due to diminished inhibin. Inhibin, a peptide, is secreted by the granulosa cells of the ovarian follicle. The increase of LH occurs subsequently.

Disturbed folliculogenesis during this period may result in anovulation, oligo-ovulation, premature corpus luteum or corpus luteal insufficiency. The sustained level of estrogens may even cause endometrial hyperplasia and clinical manifestation of menstrual abnormalities prior to menopause. The mean cycle length is significantly shorter. This is due to shortening of the follicular phase of the cycle.

Luteal phase length remaining constant. Ultimately, no more follicles are available and even some exist, they are resistant to gonadotropins Estradiol production drops down to the optimal level of 20 pg/mL → no endometrial growth → absence of menstruation.

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Following menopause, the predominant estrogen is estrone and to a lesser extent estradiol. Serum level of estrone (30–70 pg/mL) is higher than that of estradiol (10–20 pg/mL). The major source of estrone is peripheral conversion (aromatization) of androgens from adrenals (mainly) and ovaries. The aromatization occurs at the level of muscle and adipose tissue. The trace amount of estradiol is derived from peripheral conversion of estrone and androgens. Compared to estradiol, estrone is biologically less (about one-tenth) potent.

When the sources fail to provide the precursors of estrogen for around 5–10 years after menopause, there will be a significant reduce in estrogen and trophic hormones. Then it can be confirmed that the woman is in a state of true menopause.