Endogenous Progesterone and the Exogenous Progestin Norethisterone Enanthate Are Associated with a Proinflammatory Profile in Healthy Men
Open accessAbstract
CONTEXT: 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 AND DESIGN: 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. CONCLUSION: 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.
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Effects of testosterone on inflammation occur within 3-12 weeks.
“Effects on inflammation occur within 3–12 weeks.”
From Onset of effects of testosterone treatment and time span until maximum effects are achieved (2011) · cites this paper as [64]
Testosterone administration decreases IL6 after 3 weeks and after 16 weeks.
“Already after 3 weeks of testosterone administration, a decline was noted in IL6 (63) and in another study after 16 weeks (64).”
From Onset of effects of testosterone treatment and time span until maximum effects are achieved (2011) · cites this paper as [64]
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Self-citation
- Authors
- Zitzmann, M., Erren, M., Kamischke, A., Simoni, M., & Nieschlag, E.
- Affiliations
- University of Münster (DE)
- Corresponding author
- Nieschlag, Eberhard
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2005-12
- Volume
- 90
- Issue
- 12
- Pages
- 6603-6608
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- OpenAlex
- W2062689166
- Cited by
- 49
- References
- 42
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 1 · 2022: 1 · 2021: 1 · 2020: 2 · 2019: 1 · 2018: 3 · 2017: 3 · 2016: 3 · 2015: 2 · 2014: 2 · 2013: 4 · 2012: 4
- FWCI
- 1.64
- Type
- journal article
- Language
- en
- Open access
- green
- hdl.handle.net
- Licence
- cc-by
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- IRIS UNIMORE (University of Modena and Reggio Emilia) (submittedVersion, cc-by)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Keywords
- endogenous progesterone, norethisterone enanthate, progestins, inflammation, inflammatory markers, interleukin-6, C-reactive protein, soluble vascular cell adhesion molecule-1, E-selectin, leptin, neutrophils, testosterone undecanoate, androgen deficiency, male contraception, atherosclerosis risk
- MeSH terms
- Adult, Androgens, Contraceptive Agents, Male, Cross-Sectional Studies, Drug Synergism, Humans, Inflammation, Longitudinal Studies, Male, Middle Aged, Norethindrone, Progesterone, Testosterone, Biomarkers, Controlled Clinical Trials as Topic, Testosterone Congeners, Progesterone Congeners
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Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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