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Luteinizing hormone releasing hormone analogues for contraception.

Peptide contraception based on LH-RH analogues is an interesting, fundamentally new lead to fertility control in women and men. A major advantage of using peptides instead of steroids for contraception is the fact that the hypothalamic peptides exert specific actions on the hypothalamic-pituitary-gonadal system and lack systemic effects. They are therefore less likely to cause metabolic derangements and other generalized adverse effects. Antagonistic analogues of LH-RH have been synthesized but until recently they have not been potent enough for clinical trials. However, chronic treatment with low doses of superactive stimulatory analogues of LH-RH paradoxically results in desensitization of the pituitary processes responsible for gonadotrophin release. This leads to a reversible inhibition of gonadal function. In women, ovulation can be inhibited by continuous intranasal LH-RH agonist treatment. In men, higher doses of LH-RH agonists have to be administered to suppress the gonadotrophin secretion enough to affect spermatogenesis. Optimal gonadotrophin suppression is, however, accompanied by a depression of the serum concentration of testosterone with loss of libido and impotence. The superagonists of LH-RH therefore have to be administered in combination with testosterone to induce oligo- or azoospermia without impotence. The overall results of clinical trials with superagonists of LH-RH for induction of inadequate corpus luteum function, luteolysis or early abortion in women are not impressive. The contraceptive effectiveness of these approaches to peptide contraception remains to be demonstrated in the human female. Inhibition of normal ovulation can, however, be consistently achieved by daily intranasal superagonist administration in women. This approach to fertility control has already been shown to provide safe and effective contraception in women.