Hormone changes and their utility for diagnosis of menopause

During the menopause transition, the ovaries produce less and less oestradiol and progesterone, causing an increase in follicle-stimulating hormone, and a later lesser increase in luteinizing hormone  levels. After the menopause, levels of circulating oestrogen (mainly oestrone, average concentration 20 pg/ml) are much lower and are derived from the peripheral aromatization of adrenal androgens, not from the ovary. The low blood levels of oestradiol (average 13 pg/ml) in postmenopausal women are not further reduced by oophorectomy.

Although the postmenopausal ovary does not produce oestrogen, it does produce testosterone. Testosterone levels are only slightly lower in postmenopausal women with intact ovaries than in premenopausal women. Testosterone levels are much lower in women who have had bilateral oophorectomy, and somewhat lower after hysterectomy with ovarian conservation.

The menopause transition can be diagnosed clinically in the majority of women based on age, menstrual pattern, and vasomotor symptoms. Oestradiol levels are not diagnostic because striking episodic increases in oestradiol occur during this period, and postmenopausal levels may not be seen until 6 months or longer after the onset of amenorrhoea. Two serum follicle-stimulating hormone levels greater than 30 IU/ml obtained at least one month apart document that ovarian function has ceased, but this test is rarely necessary unless the woman is less than 40 years of age, has hot flushes after a hysterectomy with one ovary conserved, or her oophorectomy status is unknown. Evaluation of menopause-like symptoms accompanied by menstrual irregularities or amenorrhoea in a sexually active heterosexual woman of reproductive age should include a pregnancy test.

Symptoms

Some women sail through the menopause with no complaints; others are miserable; and most have symptoms that are somewhat bothersome. More severe symptoms follow an induced menopause. Not all symptoms that occur during the menopause transition are due to hormone changes; symptoms may in reality reflect problems with work, personal relationships, inadequate social supports, or another medical condition. The only symptoms unequivocally associated with oestrogen deficiency are those that have been consistently shown to respond better to oestrogen than to placebo in clinical trials  –  these are vasomotor and urogenital symptoms. Other common symptoms including mood swings, depression, and disturbed sleep are less consistently improved by oestrogen in controlled clinical trials.

Specific symptoms and their severity vary by ethnicity and culture, even within countries. For example, the Study of Women’s Health Across the Nation (SWAN) in the USA found that Japanese- and Chinese-American women reported menopause symptoms less frequently than Americans of northern European ancestry, while African-American women reported more vasomotor symptoms and vaginal dryness. In another North American study, symptoms were more common in women of lower socioeconomic status, women who smoked cigarettes, women who were less physically active, and (contrary to popular opinion) in overweight women. In a study of Australian women, hot flushes were reported by 27%, night sweats by 17%, vaginal dryness by 17%, and trouble sleeping by 17%.

Menses

During the menopause transition, ovarian follicles become less sensitive to circulating gonadotrophins, shortening the follicular phase and the menstrual cycle length. Nearly all women experience changes in menstrual cycles for 4 – 8 years before menopause, and any menstrual pattern is possible. Cycles become irregular and bleeding may be increased or decreased. Heavy, painful, or irregular bleeding may reflect stimulation of the endometrium by unopposed oestrogen. Sometimes women of late reproductive age miss several menstrual periods and then restart apparently normal menses.

Vasomotor symptoms

A hot flush (also called a hot flash) is a sudden wave of heat sensation, typically spreading over the upper body and face. The aetiology of hot flushes is unknown. In the USA and UK, about 30% of still regularly cycling women as young as age 35 report hot flushes. At some point in the menopause transition, hot flushes are experienced by about 75% of women. Without oestrogen therapy, hot flushes typically become less severe but persist for several years. Some women continue to report hot flushes in old age. Severe hot flushes can cause embarrassing visible changes in skin colour and sweating. Severe night sweats require change of bedding and interfere with sleep.

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