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A 25-year-old woman with menarche at 13 years and menstrual periods until about 1 year ago complains of hot flushes, skin and vaginal dryness, weakness, poor sleep, and scanty and infrequent menstrual periods of a year’s duration. She visits her gynecologist, who obtains plasma levels of follicle-stimulating hormone and luteinizing hormone, both of which are moderately elevated. She is diagnosed with ­premature ovarian failure, and estrogen and progesterone replacement therapy is recommended. A dual-energy absorptiometry scan (DEXA) reveals a bone density t-score of < 2.5 SD, ie, frank osteoporosis. How should the ovarian hormones she lacks be replaced? What extra measures should she take for her osteoporosis while receiving treatment?


The ovary has important gametogenic functions that are integrated with its hormonal activity. In the human female, the gonad is relatively quiescent during childhood, the period of rapid growth and maturation. At puberty, the ovary begins a 30- to 40-year period of cyclic function called the menstrual cycle because of the regular episodes of bleeding that are its most obvious manifestation. It then fails to respond to gonadotropins secreted by the anterior pituitary gland, and the cessation of cyclic bleeding that occurs is called menopause.

The mechanism responsible for the onset of ovarian function at the time of puberty is thought to be neural in origin, because the immature gonad can be stimulated by gonadotropins already present in the pituitary and because the pituitary is responsive to exogenous hypothalamic gonadotropin-releasing hormone. The maturation of centers in the brain may withdraw a childhood-related inhibitory effect upon hypothalamic arcuate nucleus neurons, allowing them to produce gonadotropin-releasing hormone (GnRH) in pulses with the appropriate amplitude, which stimulates the release of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) (see Chapter 37). At first, small amounts of the latter two hormones are released during the night, and the limited quantities of ovarian estrogen secreted in response start to cause breast development. Subsequently, FSH and LH are secreted throughout the day and night, causing secretion of higher amounts of estrogen and leading to further breast enlargement, alterations in fat distribution, and a growth spurt that culminates in epiphysial closure in the long bones. The change of ovarian function at puberty is called gonadarche.

A year or so after gonadarche, sufficient estrogen is produced to induce endometrial changes and periodic bleeding (menarche). After the first few irregular cycles, which may be anovulatory, normal cyclic function is established.

At the beginning of each cycle, a variable number of follicles (vesicular follicles), each containing an ovum, begin to enlarge in response to FSH. After 5 or 6 days, one follicle, called the dominant follicle, begins to develop more rapidly. The outer theca and inner granulosa cells of this follicle multiply and, under the ...

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