Effect of progesterone and its 5 alpha and 5 beta metabolites on symptoms of premenstrual syndrome according to route of administration.
Level 2 - randomized trial
Double-blind, placebo-controlled randomized crossover trial.
PubMed 8860884 · doi:10.3109/01674829609025661
What was done
Double-blind crossover trial comparing daily administration of 300 mg oral progesterone, 200 mg vaginal progesterone, and matched placebos given for 10 days premenstrually in women with premenstrual syndrome (PMS). Premenstrual distress and anxiety were assessed with validated questionnaires, and serum concentrations of progesterone and its 5-alpha and 5-beta pregnanolone metabolites were measured.
What was found
The trial was stopped early after 25 women completed treatment because statistical futility indicated no clinically meaningful difference would be detected even if sample size were doubled. Although there was an overall symptom reduction during treatment cycles, neither oral nor vaginal progesterone showed any superiority over placebo. Oral administration yielded supraphysiological levels of 5-alpha and 5-beta metabolites, and 5-alpha pregnanolone correlated negatively with anxiety, but this biological effect did not translate into greater symptom relief than placebo. Exact numeric values and confidence intervals were not reported in the abstract.
Why it matters
Shows that elevating circulating levels of neuroactive, anxiolytic progesterone metabolites via oral or vaginal progesterone does not provide symptom relief for PMS beyond the placebo response.
Limits
Small sample size (25 completers) resulting in early termination. The abstract does not report exact numerical effect sizes, variance, p-values, or baseline participant characteristics.
Cited by
- supports Topical progesterone administration does not provide the allopregnanolone neurosteroid benefit associated with other delivery forms.