Menopause

Definitions

Climacteric – phase in aging process of women marking transition from reproductive to non-reproductive stage

Menopause – final menstrual period occurring after the loss of ovarian activity; defined by loss of period for ³ 1 year.

Perimenopause – periods immediately before and after the menopause

Climacteric Syndrome – symptoms associated with climacteric. See below.

Epidemiology/Demography

Age range of menopause is 48-55 years, with median age 51 years. 1% of women get it < 40 years

Causes of early menopause–smoking, poor nutrition, high altitudes, thin, hysterectomy (compromised ovarian vasculature)

Do not cause early menopause – oral contraception, socioeconomic status, martial status, age of menarche, race, parity (# of children), height

Endocrine Changes at Menopause

Pre-Menopause (2-8 years before menopause)–Endocrine Markers: Ý FSH, ß Inhibin, Normal Estradiol and LH

Ý length of menstrual cycle, fewer follicles grow during each cycle; resolves when supply of follicles is depleted

because ovulation and corpus luteum formation may occur, pre-menopausal woman can still get pregnant

Menopause – Endocrine markers: Ý FSH (10-20x), Ý LH (3x), FSH>LH, ß Androstenedione, ß Testosterone, ß Estradiol, Estrone>Estradiol, Ý Androgen:Estrogen ratio (can cause hirsutism)

Why are FSH levels higher than LH? Because FSH has a longer half life than LH (4 hrs vs 30 mins).

Why are Androstenedione and Testosterone reduced? Adrenal gland is now the only source of androstenedione

while total testosterone is reduced because there is less conversion from androstenedione, the amount of testosterone secreted from the ovarian stroma is increased because of the elevated levels of FSH and LH.

Why is the androgen:estrogen ratio increased? Peripheral conversion of androstenedione to estrogen is now the principal source of estrogen. Though this may be significant (especially in women with Ý body weight due to aromatization of fat to androgens), it does not compare to the estrogen levels previously produced by ovary

Post-Menopause – eventually ovarian stroma is exhausted and no longer responds to FSH/LHÞ steroidogenesis stops

with age, adrenal production of estrogen precursors becomes insufficient to sustain 2^o tissues

Short-term Symptoms of Menopause

Disturbances in menstrual pattern – anovulation in pre-menopausal women, extragonadal endogenous estrogen, or estrogen administration in post-menopausal women may cause dysfunctional uterine bleeding due to excessive estrogen unopposed by progesterone; raises concern of endometrial neoplasia

Vasomotor instability – "hot flashes" are the hallmark of menopause, experienced to some degree by most women

"hot flash" – sudden onset of reddening of skin over head, neck, and chest, accompanied by feeling of intense body heat and concluded by profuse perspiration
hot flash duration – seconds-minutes (rarely an hour); frequency – can be rare or every few minutes
more severe at night and stress, less severe in cool environment
50-75% of women get hot flashes for 1-2 years, with rest > 5 years.

Physiology of Hot Flash – Not understood. Probably originates in hypothalamus as result of declined estrogen

Coincides with surge of LH (not FSH) but not dependent upon LH; same hypothalamic event that causes hot flashes also stimulates elevated LH (via GnRH)

Atrophic Changes

Vaginal Atrophy–atrophy of mucosal surfaces; accomp.by vaginitis, pruritus, dyspareunia (pain during intercourse), stenosis

Genitourinary Atrophy–mucosal thinning of urethra and bladder; leads to urethritis with dysuria, urgency, incontinence, Ý urinary frequency

Skin Atrophy - ß skin collagen and ß skin thickness.

Psychophysiologic effects – Fatigue, nervousness, headaches, insomnia, depression, irritability, joint and muscle pain, dizziness, and palpitations are associated with early post-menopause

hot flashes during sleep may disturb REM sleep leading to emotional instability during wake hours

Long-term Consequences of Menopause

Osteoporosis – Progressive loss of bone mass leading to Ý in fractures

after menopause up to 5% of trabecular bone and 11.5% of total bone mass lost per yr (slower in African-Americans)

risk of fracture depends on bone mass at time of menopause and rate of bone loss following menopause.

ß bone mass with: Ý age, ß parity, early menopause, race (white>black), small frame, family history, lack of physical activity, smoking, EtOH, caffeine

Prevention–Ý wt bearing activities, stop smoking, minimize EtOH, ß body weight, adequate Ca²⁺ (1g/day), estrogen

Treatment – estrogen, calcitonin, Na⁺ fluoride, bisphosphonates, Vit D, Selective Estrogen Receptor Modulators (SERM)

Cardiovascular Disease – #1 killer of women in the U.S. Due to Ý LDL and total triglyceride levels, ß HDL levels.

beneficial actions of estrogens on cardiovascular disease:

(1) reverses lipid changes

(2) has direct antiatherosclerotic effects on arteries

(3) augments vasodilating and anti-platelet aggregation factors (NO, prostacyclin, etc.)

(4) has direct inotropic effect on heart

(5) improves peripheral glucose metabolism with subsequent ß circulating insulin

(6) inhibits lipoprotein oxidation