Comparison of metabolic effects of the progestational androgens dimethandrolone undecanoate and 11β-MNTDC in healthy men

Abstract

Background: Dimethandrolone (DMA) and 11β-methyl-19-nortestosterone (11β-MNT) are two novel compounds with both androgenic and progestational activity that are under investigation as potential male hormonal contraceptives. Their metabolic effects have never been compared in men.

Objective: Assess for changes in insulin sensitivity and adiponectin and compare the metabolic effects of these two novel androgens.

Materials/methods: In two clinical trials of DMA undecanoate (DMAU) and 11β-MNT dodecylcarbonate (11β-MNTDC), oral prodrugs of DMA and 11β-MNT, healthy men received drug, or placebo for 28 days. Insulin and adiponectin assays were performed on stored samples. Mixed model analyses were performed to compare the effects of the two drugs. Student's t test, or the non-parametric Kruskal-Wallis test as appropriate, was used to evaluate for an effect of active drug versus placebo.

Results: Class effects were seen, with decrease in HDL-C and SHBG, and increase in weight and hematocrit, with no statistically significant differences between the two compounds. No changes in fasting glucose, fasting insulin, or HOMA-IR were seen with either compound. There was a slight decrease in adiponectin with DMAU that was not seen with 11β-MNTDC. An increase in LDL-C was seen with 11β-MNTDC but not with DMAU.

Discussion: There were no significant changes in insulin resistance after 28 days of oral administration of these novel androgens despite a mild increase in weight. There may be subtle differences in their metabolic impacts that should be explored in future studies.

Conclusion: Changes in metabolic parameters should be carefully monitored when investigating androgenic compounds.

Trial registration: ClinicalTrials.gov NCT01382069 NCT02754687.

Keywords: androgen; male hormonal contraception; progestin.

© 2021 American Society of Andrology and European Academy of Andrology.

Figures

Fig. 1.

Participant Disposition: (A) DMAU, (B) 11β-MNTDC

Fig. 1.

Participant Disposition: (A) DMAU, (B) 11β-MNTDC

Fig. 2.

Changes in weight from Day 1 to Day 28. There was a significant dosage group effect seen (pth and 75th percentiles; whiskers display the smallest and largest values at most 1.5 times the interquartile range (IQR) of the hinge. Values more than 1.5 IQR are shown as specific points in the graph.)

Fig. 3.

Changes in metabolic parameters from Day 1 to to Day 28. (A) Fasting glucose: There was no significant effect of dosage group, androgen type, or dosage-drug interaction. (B) Fasting insulin: Two participants with biologically implausible insulin levels were excluded. There was no significant effect of dosage group, androgen type, or dosage-drug interaction. (C) Fasting insulin resistance as calculated by HOMA-IR. Two participants with biologically implausible insulin levels were excluded. There was no significant effect of dosage group, androgen type, or dosage-drug interaction. (D) Adiponectin: There was no significant effect of dosage group, androgen type, or dosage-drug interaction. There was a decrease in adiponectin in participants receiving DMAU active drug compared to placebo (p

Fig. 4.

Changes in lipids from Day 1 to Day 28. (A) HDL-Cholesterol: There was a significant dosage group effect seen (p

Fig. 5.

Changes in parameters affected by androgens from Day 1 to Day 28. (A) Hematocrit: There was a significant dosage group effect seen (p