Abstract
The current understanding of androgen estrogenand gonadotropin metabolism in menopausal women is reviewed. In young women the principal ovarian androgen is androstenedione (mean concentration 1500 pg/ml; range 500-3000 pg/ml; and production rate 3 mg in 24 hours). During the menstrual cycle its concentration is 15% higher at midcycle. Increased ovarian secretion is thought to cause this increase. In blood androstenedione is bound loosely to albumin and minimally to sex-hormone-binding globulin (SHBG). The circulating level of testosterone ranges from 200 to 600 pg/ml. Its mean concentration is 20% higher at midcycle. Testosterone is bound extensively to globulin. The average production rate of testosterone is 250 mcg in 24 hours. Of circulating androstenedione 14% is converted to testosterone accounting for 50% of circulating testosterone. After ovariectomy androstenedione of adrenal origin accounts for most of the testosterone. The remainder is the result of direct adrenal secretion of testosterone. In normal postmenopausal women the mean androstenedione concentration is half the concentration found in intact premenopausal women and is similar to that in younger patients after ovariectomy. The clearance rate is the same in older and in younger women. In postmenopausal women ovariectomy results in a small but significant decrease in circulating androstenedione. The adrenal glands secrete comparable amounts of androstenedione before and after the menopause. For testosterone the mean concentration is lower in postmenopausal women but higher than after ovariectomy in young women. The clearance rate does not change. In young women the principal circulating estrogen is 17beta-estradiol. Its level fluctuates widely during each cycle with the highest level prior to ovulation. Estradiol is also bound to SHGB. The production rate varies greatly during each cycle. Most estradiol is secreted by the ovary. Postmenopausal estradiol levels are low and the clearance level is reduced. Estrone levels vary during the menstrual cycle. It is not bound to the SHGB. The metabolic clearance rate is rapid and the production rate changes during the cycle. In postmenopausal women the clearance rate of estrone is lower. The source is then from the peripheral conversion of androstenedione. In postmenopausal women with endometrial cancer or endometrial hyperplasia excessive conversion has been shown with increased estrone production. In cancer patients excessive body weight seemed to be a factor in increasing circulating levels of these hormones. As women approach the menopause follicle stimulating hormone levels rise while luteinizing hormone (LH) levels tend to remain the same. In postmenopausal women both levels are significantly elevated. Marked pulsatile variations in gonadotropin release have been observed. Low estrogen levels are thought to cause increased responsiveness of the pituitary to LH-releasing factor. Endometrial cancer patients may have different gonadotropin activity.
Published Version
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