Endogenous progesterone and the exogenous progestin norethisterone enanthate are associated with a proinflammatory profile in healthy men.
BACKGROUND
Inflammatory processes are related to atherosclerosis. Identification of inflammation triggers may furnish new therapeutic pathways. In women, progestins can have a marked inflammatory capacity.


OBJECTIVE
We investigated the effects of progesterone in men within the setting of two independent trials. First, the relation of endogenous progesterone levels to inflammation markers was assessed in 67 healthy nonsmoking Caucasian men (age, 20-50 yr) on a cross-sectional basis. Second, in a longitudinal controlled trial (52 wk) involving 28 healthy men receiving i.m. medication, we determined the effects of an exogenous progestin (norethisterone enanthate 200 mg) in combination with a long-acting testosterone preparation (testosterone undecanoate 1000 mg) administered to avoid androgen deficiency caused by pituitary-hypothalamic feedback. Controls received testosterone plus placebo.


RESULTS
In the cross-sectional study, progesterone levels were positively related to concentrations of IL-6 (r = 0.41; P < 0.001), C-reactive protein (r = 0.37; P = 0.007), soluble vascular cell adhesion molecule 1 (r = 0.28; P = 0.02), E-selectin (r = 0.45; P < 0.001), leptin (r = 0.42; P < 0.001), neutrophils (r = 0.62; P < 0.001), and serum protein fractions alpha-1 (r = 0.44; P < 0.001) and alpha-2 (r = 0.36; P = 0.002). During the pharmacological trial, the testosterone/progestin group exhibited a marked increase of IL-6 concentrations (P < 0.001), whereas these decreased in the testosterone/placebo group (P = 0.03). Antiinflammatory IL-10 levels decreased in the group receiving testosterone/progestin (P = 0.01) but did not change in the testosterone/placebo group.


CONCLUSIONS
Progesterone concentrations correspond to an inflammatory profile in healthy men, and external progestins elicit a similar effect. Men receiving regimens for hormonal male contraception involving progestins should be monitored for inflammatory effects. Speculatively, testosterone treatment decreasing endogenous progesterone production may facilitate beneficial effects on inflammation profiles even in eugonadal men.
Zitzmann
Michael
M
Institute of Reproductive Medicine of the University, Domagkstrasse 11, D-48129 Münster, Germany.
Erren
Michael
M
Kamischke
Axel
A
Simoni
Manuela
M
Nieschlag
Eberhard
E
D000328:Adult; D000728:Androgens / Q000378:metabolism*; D015415:Biomarkers / Q000097:blood; D003272:Contraceptive Agents, Male / Q000494:pharmacology; D018849:Controlled Clinical Trials as Topic; D003430:Cross-Sectional Studies; D004357:Drug Synergism; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000139:chemically induced / Q000209:etiology* / Q000378:metabolism; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009640:Norethindrone / Q000031:analogs & derivatives* / Q000494:pharmacology; D011374:Progesterone / Q000097:blood / Q000502:physiology*; D045167:Progesterone Congeners / Q000494:pharmacology; D013739:Testosterone / Q000031:analogs & derivatives* / Q000494:pharmacology; D045165:Testosterone Congeners / Q000494:pharmacology*
D000728:Androgens; D015415:Biomarkers; D003272:Contraceptive Agents, Male; D045167:Progesterone Congeners; D045165:Testosterone Congeners; D013739:Testosterone; D011374:Progesterone; C010792:testosterone undecanoate; C024319:norethindrone enanthate; D009640:Norethindrone