CAG repeat length in the androgen receptor gene and gonadotrophin suppression influence the effectiveness of hormonal male contraception.
OBJECTIVE
Nonuniformity in suppression of spermatogenesis induced by various hormones or hormone combinations has impeded the development of an effective hormonal male contraceptive. The basis for this heterogeneity in response remained unresolved to date; however, the presence of ethnic differences points to an involvement of genetic factors.


METHODS
In a retrospective analysis we investigated the impact of a CAG repeat polymorphism in the androgen receptor and polymorphic sites in the oestrogen and FSH receptor genes on spermatogenic suppression in 85 Caucasian men treated with different regimens of hormonal contraception.


RESULTS
Failure to reduce sperm concentrations below 3 million/ml was significantly associated with insufficient suppression of gonadotrophins. The extent of gonadotrophin suppression was not explained by any polymorphism but was primarily pharmacological, resulting from addition of gestagens to testosterone. When LH and FSH suppression was rapid and persistent none of the polymorphisms studied explained why some men failed to achieve azoospermia. In cases with incomplete gonadotrophin suppression the chances of becoming azoospermic were 2.5 times higher in men having more than 22 CAG repeats.


CONCLUSIONS
In summary, our analysis shows that in a subset of men, effective hormonal male contraception can be achieved even in the absence of complete gonadotrophin suppression.
Eckardstein
Sigrid V
SV
Institute of Reproductive Medicine of the University, Münster, Germany.
Schmidt
Anja
A
Kamischke
Axel
A
Simoni
Manuela
M
Gromoll
Jörg
J
Nieschlag
Eberhard
E
D000328:Adult; D016009:Chi-Square Distribution; D003272:Contraceptive Agents, Male / Q000008:administration & dosage*; D003278:Contraceptives, Oral, Hormonal / Q000008:administration & dosage*; D003864:Depression, Chemical; D047628:Estrogen Receptor alpha; D006065:Gonadotropins, Pituitary / Q000097:blood; D006801:Humans; D008297:Male; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D011944:Receptors, Androgen / Q000235:genetics*; D011960:Receptors, Estrogen / Q000235:genetics; D011962:Receptors, FSH / Q000235:genetics; D012091:Repetitive Sequences, Nucleic Acid; D012189:Retrospective Studies; D013076:Sperm Count; D013091:Spermatogenesis / Q000187:drug effects*; D018709:Statistics, Nonparametric
D003272:Contraceptive Agents, Male; D003278:Contraceptives, Oral, Hormonal; D047628:Estrogen Receptor alpha; D006065:Gonadotropins, Pituitary; D011944:Receptors, Androgen; D011960:Receptors, Estrogen; D011962:Receptors, FSH