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Randomised trial, 2006

Do women with PMDD and depression process progesterone differently than others?

Yes. Women with prior depression convert progesterone to its active form less efficiently. Women with PMDD and no depression history show unusual patterns of this conversion, suggesting altered metabolic pathways.

Moderate study design 23 women with premenstrual dysphoric disorder and 29 without, about half of each group with prior depression history

What they did

23 women with PMDD and 29 without PMDD (about half in each group had prior depression) received a double-blind placebo-controlled 300 mg dose of oral micronized progesterone. Researchers measured progesterone and its metabolite allopregnanolone at four time points (160, 190, 225, and 255 minutes after dosing).

What they found

Women with prior depression had lower allopregnanolone levels and marginally lower progesterone levels after the dose, especially non-PMDD women with depression. PMDD women without prior depression had unusually high allopregnanolone-to-progesterone ratios. All women reported increased confusion, fatigue, and reduced confidence after progesterone administration, even accounting for placebo effects.

What it means for you

Depression history may reduce how efficiently the body converts progesterone into its active form, which could explain why some women with PMDD don't respond well to progesterone treatment. The temporary mood worsening from the progesterone dose itself is concerning and needs further study. This was a small acute-dosing study.

23

women with PMDD

29

women without PMDD

300 mg

progesterone dose

About the study

Original title
Associations of histories of depression and PMDD diagnosis with allopregnanolone concentrations following the oral administration of micronized progesterone
Authors
Klatzkin RR, Morrow AL, Light KC et al.
Journal
Psychoneuroendocrinology
Year
2006
Study design
Randomised trial
What was tested
Single 300 mg oral dose of micronized progesterone under double-blind placebo-controlled conditions

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