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dc.contributor.authorWalton, Melanie Janeen
dc.date.accessioned2018-03-29T12:20:49Z
dc.date.available2018-03-29T12:20:49Z
dc.date.issued2008
dc.identifier.urihttp://hdl.handle.net/1842/29411
dc.description.abstracten
dc.description.abstractThe principle of male hormonal contraception has been investigated for the past 20 years. This thesis reviews what is known already from the literature and presents the results of three new clinical trials investigating different aspects of this approach.en
dc.description.abstractThese trials were undertaken by myself as a member of the Contraceptive Development Network research group at the University of Edinburgh.en
dc.description.abstractMOIS: A clinical trial of male hormonal contraception with a treatment period of 48 weeks. Subjects (n=29) were randomised to receive either 2 MENT Ac implants or 600mg per 12 weeks testosterone pellets in conjunction with 2 etonogestrel implants and outcome measures of sperm count, and reproductive hormone data were collected to assess contraceptive effects. Haematology and biochemistry parameters, prostate volume, PSA, bone density and blood pressure measurements were recorded to assess safety and the effects on androgen dependent tissues. The spermatogenic suppression achieved was similar and effective in both groups. Thereafter, the MENT group failed to maintain suppression and 6 men nnoted loss of libido due to a decline in the release rate of the MENT implants. No adverse effects of MENT on the prostate or bone mass were demonstrated. A small but significant increase in systolic blood pressure was observed in the MENT group and the implications of this remain to be further qualified. In the testosterone group profound and consistent spermatogenic suppression was demonstrated and azoospermia was achieved in all men. An increase in haemoglobin and prostate size and reduction in HDL-C were noted. MENT with progestogen can achieve rapid suppression of spermatogenesis similar to testosterone, but this promising result was not sustained due to a reduction in the MENT release from the implants. This dose of testosterone, compared with previous studies using lower dose with a higher dose of etonogestrel, had non-reproductive side effects without any increase in spermatogenic suppression.en
dc.description.abstractConclusion: These data indicate the importance of the doses of progestogen and testosterone for optimum spermatogenic suppression while minimizing side effects.en
dc.description.abstractM016: A randomised controlled trial investigating the effects of gonadotrophin withdrawal and progestogen administration on hormone production, metabolism and action in the human testis. Thirty subjects were randomised to no treatment or gonadotrophin suppression by GnRH antagonist with testosterone (CT) +/- additional administration of the progestogen desogestrel (CTD) for 4 weeks before testicular biopsy. Gene expression was quantified by PCR. Both treatment groups showed similar suppression of gonadotrophins and sperm production and markedly reduced expression of steroidogenic enzymes. Addition of progestogen resulted in expression of 5a-reductase type 1 compared with both controls and the CT group. Inhibin-a and the spermatocytes marker acrosin-binding protein were significantly lower in the CTD but not CT groups, compared with controls, but did not differ between treated groups. Men who showed greater falls in sperm production also showed reduced expression of these three genes but not of the spermatid marker protamine 1.en
dc.description.abstractConclusion: These data provide evidence for direct progestogenic effects on the testis and highlight steroid 5a-reduction and disruption of spermiation as important components of the testicular response to gonadotrophin withdrawal.en
dc.description.abstractM017: Investigation of testicular function in normal men and those receiving a male hormonal contraceptive regimen. 20 subjects were recruited and hourly blood samples were taken over 24 hours for measurement of testosterone, inhibin B, LH, FSH and Cortisol. Urinary excretion of testosterone and the testicular steroid epitestosterone was also measured. In the controls, a diurnal variation in serum testosterone and LH but not FSH was detected. The treated group had similar testosterone concentrations but showed no diurnal variation. Periodicity was detected in inhibin B concentrations in 5 controls and in 9 of the treated group. Urinary testosterone excretion did not show a diurnal variation in either group, but this was apparent for epitestosterone with a morning peak in both groups despite the markedly lower excretion in the treated men.en
dc.description.abstractConclusion: The diurnal variation of testosterone in normal men is due to change in secretion rather than clearance and is largely LH driven. An endogenous rhythm in both testicular steroidogenesis (epitestosterone) and Sertoli cell function (Inhibin B) is also present.en
dc.publisherThe University of Edinburghen
dc.relation.ispartofAnnexe Thesis Digitisation Project 2018 Block 17en
dc.relation.isreferencedbyAlready catalogueden
dc.titleNovel approaches to male hormonal contraceptionen
dc.typeThesis or Dissertationen
dc.type.qualificationlevelDoctoralen
dc.type.qualificationnameMD Doctor of Medicineen


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