Menopause

Menopause is the permanent cessation of menstruation resulting from the loss of ovarian function. Throughout reproductive life the number of follicles decreases. This process accelerates in the late thirties. Inhibin levels produced by the granulosa cells gradually reduce leading to rise in FSH. Raised FSH leads to increased estradiol production by the ovaries for a few years preceding actual menopause, which can cause menstrual irregularities. More cycles become anovulatory. Mean follicular phase and menstrual cycle length may be reduced before menopause. At first, the luteal phase is of normal duration, but luteal dysfunction eventually may occur because of a fall in progesterone levels. Finally, estradiol and inhibin levels decline while FSH and LH remain elevated. Gonadotropin levels greater than 30 mIU/ml are typically diagnostic of menopause, with the ratio of FSH to LH being greater than 1.

The estrogen produced after menopause is primarily from the peripheral conversion of adrenal androgens and occurs in the liver, kidney, brain, adrenal, and peripheral adipose tissue. Estradiol is present in low levels too, from peripheral conversion of estrone. Obese women have a higher concentration of free estradiol because of decreased sex hormone-binding globulin and an increased rate of aromatization.

Menopause is associated with vasomotor disturbances characterized by hot flashes, genital atrophy and psychologic symptoms. The decline in estrogen also causes an increased risk of osteoporosis. Vasomotor instability appears to arise not from a lack of estrogen but rather from its withdrawal. Flashes appear to be more severe at times of stress and more frequent and severe at night, when they are called night sweats. Hot flashes are accompanied by pulses of LH and increase in the levels of ACTH, cortisol, dehydroepiandrosterone and androstenedione.

Common risk and protective factors for osteoporosis

Unavoidable Risk Factors	Avoidable Risk Factors	Protective Factors
Genetic predisposition	Lack of physical exercise	Obesity
Low bone mass	Insufficient calcium intake	Multiparity
Slender build	Smoking	Muscular habitus
White or Asian race	Excessive alcohol intake	Black race
Premature ovarian failure	Excessive caffeine intake	Prolonged oral contraceptive use
Surgical menopause	Estrogen deficiency	Hormone replacement therapy
Glucocorticoid therapy	Anorexia nervosa
Nulliparity	Excessive exercise
	Excessive thyroid replacement

Testicular function

Testosterone is secreted by the Leydig cells of the testes. The testicular enzyme 17 beta hydroxysteroid dehydrogenase converts androstenedione to testosterone. The enzyme 5 alpha reductase converts testosterone to dihydrotestosterone or DHT. Testosterone circulates in the plasma bound to sex hormone binding globulin and albumin. Only free hormone is biologically active. Pulsatile release of GnRH stimulates the release of FSH and LH from the anterior pituitary. FSH stimulates spermatogenesis and Sertoli cell function. LH stimulates Leydig cells to synthesize testosterone. Testosterone has both paracrine and endocrine effects. It supports Leydig cell function and promotes spermatogenesis. Testosterone exerts negative feedback on both the hypothalamus and anterior pituitary to inhibit the secretion of GnRH and LH respectively. Sertoli cells secrete inhibin which inhibits FSH secretion from the anterior pituitary. Sertoli cells also secrete AMH or anti-mullerian hormone which causes atrophy of the mullerian ducts.

Actions of testosterone

Differentiation of male internal genitalia - the epididymis, vas deferens, seminal vesicles
Stimulates growth and development of the Wolffian ducts
Increase in muscle mass
Pubertal growth spurt, closure of epiphysis, deepening of voice
Libido
Stimulates spermatogenesis

Actions of DHT

Differentiation of male external genitalia
Male pattern hair distribution, male pattern hair loss
Prostate growth
Acne and increased sebaceous gland activity