Hypothalamic Dysfunction Gonadotropin Secretion and Weight Loss

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It is now recognized that the amenorrhea of underweight and excessively lean women is due to hypotha-lamic dysfunction. Hypothalamic dysfunction has also been implicated in the amenorrhea of athletes. Consistent with the view that this type of amenorrhea is adaptive, the pituitary-ovarian axis is apparently intact and functions when exogenous gonadotropin-releasing hormone (GnRH) is given in pulsatile form or in a bolus.

Women with this type of hypothalamic amenor-rhea have both quantitative and qualitative changes in the secretion of the gonadotropins, luteinizing hormone (LH) and follicle-stimulating hormone (FSH), and of estrogen:

1. Levels of LH, FSH, and estradiol levels are low.

2. The secretion of LH and the response to GnRH are reduced in direct correlation with the amount of weight loss.

3. Underweight patients respond to exogenous GnRH with a pattern of secretion similar to that of prepubertal children; the FSH response is greater than the LH response. The return of LH responsiveness is correlated with weight gain.

4. The maturity of the 24-h LH secretory pattern and body weight are related. Weight loss results in an age-inappropriate secretory pattern resembling that of prepubertal or early pubertal children. Weight gain restores the postmenarcheal secretory pattern.

5. A reduced response or absence of response to clomiphene, a pituitary hormone which stimulates ovulation, is correlated with the degree of the loss of body weight and hence of fat. A normal response occurs after weight gain to the normal range.

Supportive of the view that this type of hypotha-lamic amenorrhea is adaptive is the finding of one study that women in whom ovulation had been induced had a higher risk of having babies who were small for their age, and this risk was greatest (54%) in those who were underweight. The authors of this study concluded that the most suitable treatment for infertility secondary to weight-related amenorrhea is dietary rather than induction of ovulation.

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