Menopause pathophysiology

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

Overview

Menopause is natural amenorrhea that is happened without any pathological causes, but premature menopause/early menopause caused by pathological diseases in ovaries include premature ovarian failure termed as Primary ovarian insufficiency (POI), several medical condition such as Adrenal insufficiency, type1 diabetes mellitus, Autoimmune thyroid disease, Fragile X Syndrome, Fanconi’s anemia, Congenital adrenal hyperplasia, and Turner’s syndrome. The most important Conditions associated with Menopause are Cardiovascular disease and Osteoporosis. Under microscope the structures of the ovaries are change, The cortex becomes thinner and it has fewer follicles, the medulla develops stromal fibrosis and scars. The mucosa layer of the vagina begins to atrophy due to decreased estrogen.

Pathophysiology

Physiological menopause

• 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.

Decrease of anterior pituitary gonads hormones during the menopause transition result from decreased ovarian feedback of inhibin and are manifested primarily as elevations in follicle-stimulating hormone (FSH). Adrenal changes concurrent with the menopause transition include elevations in serum cortisol and transient elevations in dehydroepiandrosterone sulfate, androstenediol, and other adrenal androgens"

Pathological menopause

Premature menopause/early menopause caused by:

• Pathological disease in ovaries include premature ovarian failure termed as Primary ovarian insufficiency (POI).(POI) 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.
• Premature menopause is a result of several medical condition such as Autoimmune disease(Adrenal insufficiency, type1 Diabetes mellitus, Autoimmune thyroid disease), Fragile X Syndrome, Fanconi’s anemia, Congenital adrenal hyperplasia due to 17α-hydroxylase deficiency.

Genetic

• 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.
• Turner’s syndrome: "Women born with missing chromosomes or problems with chromosomes can go through menopause early, women are born without all or part of one X chromosome, so their ovaries do not form normally at birth and their menstrual cycles, including the time around menopause, may not be normal"

Associated Conditions

The most important Conditions associated with Menopause include:

• Cardiovascular disease: " Estrogen has a positive effect on the tunica intima of the artery wall, helping to keep blood vessels flexible. During menopause, estrogen deficiency causes vasoconstriction of the vessel wall and an accelerated increase of low-density lipoprotein (LDL). Thus, 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, such that there is an imbalance of osteoclastic and osteoblastic activity. This results in more bone being reabsorbed and overall bone loss.  Estrogen deficiency leads to the release of cytokines among them RANKK ligand (RANKL), which plays a critical role in the osteoclastogenesis cascade. During menopause, women experience an increased rate of bone loss of 3% to 5% per year for 5 to 7 years".

Microscopic Pathology

On microscopic histopathological of menopause:

• "Structures of the ovaries are change, the distinction between the cortex and medulla is less evident. The cortex becomes thinner, it has fewer follicles that is the tendency towards the fragmentation of the corpora arenacea. Additionally, there are invaginations of the surface epithelium of the cortex, and epithelial inclusion cysts are present".

• "The medulla develops stromal fibrosis and scars. The medulla also undergoes the hyalinization of vessel walls, with architectural changes of vessels".

• "There is also a significant change in the vagina during menopause, the mucosa layer of the vagina begins to atrophy due to decreased estrogen that causes this cell layer to become drier and thinner. As a result, the vaginal mucosa loses its elasticity and becomes fragile".