Endocrine Abstracts (2002) 3 OC37

Demonstration of progesterone receptor mediated gonadotrophin suppression in men

BM Brady1, RA Anderson2, D Kinniburgh1 & DT Baird1

1Contraceptive Development Network, The University of Edinburgh, Scotland, UK; 2MRC Human Reproductive Sciences Unit, Edinburgh, Scotland, UK.

Synthetic C19 gestogens which are used in combination with testosterone as hormonal contraception in men bind to both the androgen and progesterone receptor. The relative contribution of these two components is unclear. In this study, we have compared the effect of a synthetic gestogen (desogestrel) with naturally occurring progesterone on the pattern of secretion of LH and FSH in healthy volunteers. Twenty men aged 18-40 were randomised to receive either progesterone (gestone) 50 mg im or desogestrel 300mcg orally daily for 7 days. Frequent blood sampling (15 minute intervals) was performed for 12 hours pre and post-treatment, with administration of 100mcg GnRH iv after 10 hours. There was a significant decline in overall mean gonadotrophin levels with both treatments. LH fell from 2.92±0.71 to 1.57±0.32 (p=0.001) after progesterone and from 2.58±0.39 to 1.42±0.36IU/L (p=0.002) after desogestrel. FSH fell from 2.14±0.22 to 1.09±0.15 (p=0.003) after progesterone and from 2.88±0.34 to 1.48±0.2IU/L (p<0.0001) after desogestrel. Progesterone treatment also resulted in a significant decrease in LH pulse frequency (number of pulses/10hrs) from 4.7±0.4 to 3.8±0.4 (p=0.002) and pulse amplitude from 2.4±0.5 to 1.6±0.4IU/L (p=0.02). Similarly, after desogestrel there was a decrease in pulse amplitude from 1.9±0.2 to 1.3±0.3IU/L (p=0.04) however there was a non-significant decrease in pulse frequency from 3.50±0.2 to 3.0±0.3 (p=0.3). There was a significant attenuation of the gonadotrophin response to GnRH in the progesterone group from 16.3±4.3 to 10.5±2.6IU/L (LH, p=0.0003) and from 3.6±0.3 to 2.0±0.2 (FSH, p=0.0006) with a non-significant decline following desogestrel. There was a significant fall in mean testosterone concentrations with both treatments. These results indicate that progesterone inhibits gonadotrophin production at both the hypothalamus (pulse frequency) and anterior pituitary. In addition to interacting with the androgen receptor, synthetic gestogens also mediate their antigonadotrophic effect through the progesterone receptor.

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