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Title: Studies in male hormonal contraception
Author: Hair, W. Morton
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2004
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To date androgens remain a central part of any hormonal contraceptive for men although understanding the heterogeneity of the suppression response within populations may require consideration of less orthodox hormonal regulatory systems. Development of minimally invasive, long acting androgen formulations is also necessary to provide an acceptable, convenient and reliable form of androgen delivery which men themselves can administer. Experimental studies in animals have established prolactin as a progonadal hormone in the testis and accessory glands. To explore the role of prolactin in men we investigated the localization and functional activation of the prolactin receptor in the human testis and accessory tissues by immunohistochemistry, RT-PCR and activation of the Janus Kinase/Signal Transducer and Activator of Transcription and Mitogen Activated Protein kinase and Extracellular signal-Regulated Kinase signalling pathways. Expression of prolactin receptor was localized to the Leydig cells and differentiating cells of the testis, the epithelium of vas deferens, epididymis, prostate and seminal vesicles. Functional activation of prolactin receptor was demonstrated in fresh samples of vas deferens. The second study investigated whether concomitant suppression of PRL with the dopamine receptor agonist quinagolide (Q), would enhance the efficacy of testosterone (T) as a contraceptive in men. Volunteers were treated orally with Q, to chronically suppress PRL secretion. A high and an intermediate dose of T was selected to establish whether PRL inhibition would allow use of a lower dose of androgen to induce azoospermia in men. Q did not seem to confer additional efficacy but difficulties in chronic suppression of PRL precludes definitive assessment. The final study describes a clinical trial employing a subject administered, non-invasive hormonal contraceptive regime. Men received transdermal T patches and the synthetic progestagen desogestrel orally in a down ward dose finding study. Transdermal T was less effective than injectable androgen formulations and the minimally effective dose of DSG is 150 mg/day.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available