Menopause pathophysiology

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Rahmah Al-Edresi, M.D.[2]

Menopause is natural amenorrhea that is happened without any pathological causes, but premature menopause/early menopause is caused by pathological diseases in ovaries and other organs such as premature ovarian failure (Primary ovarian insufficiency, POI), Adrenal insufficiency, type1 diabetes mellitus, autoimmune thyroid disease, Fanconi’s anemia, and Congenital adrenal hyperplasia. Cardiovascular disease and osteoporosis are most important conditions associated with menopause. Women who had genetic disorders ( Fragile X syndrome, Turner’s syndrome) more prone able to early menopause. The histopathological analysis include ovaries‘s cortex becomes thinner and it has fewer follicles and the medulla develops fibrosis and scars. Decrease of ciliated cells of Fallopian tubes and Uterus. And atrophy of vaginal mucosal layer .

• Menopause happens normally as women age and the main cause of the menopause is the natural shortage of the primordial follicles (oocytes) that stored in the ovaries and the decrease of the response of ovaries to anterior pituitary gonads hormones that include Follicle Stimulating Hormone (FSH) and Luteinizing Hormone(LH).
• These hormones stimulate the ovaries to produce estrogen and progesterone hormones in a cyclic method under the control of the hypothalamus that produces the gonadotropin-releasing hormones which stimulate anterior pituitary gonads hormone secretion and inhibin-B that plays role in the feedback mechanism.
• The anterior pituitary gonads hormones is decreased during the menopause transition result from decreased ovarian feedback of inhibin and are manifested primarily as elevations in follicle-stimulating hormone (FSH).^[1]

Premature menopause/early menopause is caused by several pathological diseases include:

• Pathological disease in ovaries include premature ovarian failure termed as primary ovarian insufficiency (POI). It is the loss of ovarian function lead to amenorrhea because of ovarian failure to respond for gonads hormone ( FSH, LH) and deficiency production of estrogen and progesterone hormone.
• Pathological disease in other organs such as Adrenal insufficiency, type1 Diabetes mellitus, Autoimmune thyroid disease, Fanconi’s anemia, Congenital adrenal hyperplasia due to 17α-hydroxylase deficiency.^[2][3]

There are genetic disorders involved in the premature menopause/early menopause include:

• Fragile X syndrome is a genetic disorder characterized by reduction of ovarian function, women that have Fragile X Syndrome go through early menopause an average 5 years early than other women.^[4]
• Turner’s syndrome: women born with missing X chromosome can go through menopause early, due to their ovaries do not form normally at birth.^[5]

The most important Conditions associated with Menopause include:

• Cardiovascular disease: during menopause, estrogen deficiency causes vasoconstriction of the vessel wall. menopause is linked to the increased risk of cardiovascular disease.

• Osteoporosis is a disease of the bones that causes bones to become weak and break easily. During menopause, estrogen deficiency increases osteoclastic activity.^[6]

On microscopic histopathological analysis of menopause include:

• Ovaries: the ovaries’s structure are change, the difference between the cortex and medulla is less evident. The cortex becomes thinner, it has fewer follicles. And there are invaginations of the surface epithelium of the cortex.The medulla develops fibrosis and scars, also undergoes the hyalinization of vessel walls.
• Fallopian tubes and Uterus: both endometrial and tubal mucosa demonstrated a gradual decrease in the number of ciliated cells and the non ciliated cells of the uterus.

• Vagina: the mucosa layer begins to atrophy due to decreased estrogen that causes this layer to become drier and thinner.^[7][8]

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