This project is designed to determine the response to varying degrees of GnRH receptor blockade in normal men and women, postmenopausal women and patients with reproductive endocine disorders. This has been an extremely active protocol and a significant number of publications have resulted from these studies. In the past year, the investigators have completed their studies in GnRH deficient men, a model in which it is possible to quantitate the relationship between GnRH and GnRH receptor blockade. Two manuscripts resulting from these studies are currently in review. This study provides important validation for previous studies in which the investigator has used submaximal GnRH receptor blockade to estimate the overall amount of endogenous GnRH sereted in subjects across the menstrual cycle and at the midcycle surge. In addition, in this past year the investigators have published their studies in patients with polycystic ovarian syndrome (PCOS) in which they showed that the LH response to incomplete receptor blockade was not different than in women in the follicular phase. These data suggest that the increased frequency of pulsatile GnRH secretion, which they had previously found in PCOS, is not associated with an overall increase in the amount of GnRH secreted. Complete GnRH receptor blockade was used to examine the effect of LH on androgen secretion in acute and short-term studies. Results provided further evidence for dependence of androgen secretion on LH, but also indicated that testosterone levels decreased by only 40%, even with 7 days of LH inhibition.
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