Hormonal shifts throughout a woman's life — from first periods through menopause — can play a meaningful role in mood and depression risk. This review brings together research on how estrogen and progesterone influence mental health at each major stage, including the menstrual cycle, contraceptive use, pregnancy, and the transition to menopause.
For those living with PMDD, an important takeaway is that the review confirms the condition is not caused by having too much or too little of any hormone. Instead, it appears that some women's brains are more sensitive to normal hormonal changes, particularly the rise and fall of progesterone and its brain-active byproduct, allopregnanolone, during the luteal phase. About 5-8% of women are affected by PMDD. Animal studies have shown that mimicking the progesterone drop that happens before a period can produce depression-like and social withdrawal behaviors, supporting what many people with PMDD experience firsthand.
The review also highlights connections across life stages. Women who are sensitive to hormonal shifts at one point in life — such as during the menstrual cycle — may face higher risk during other transitions like pregnancy or menopause. A personal history of depression is consistently the strongest predictor of future mood episodes during any hormonal transition. On a hopeful note, newer hormonal treatments are emerging: brexanolone, an injectable form of allopregnanolone, was approved in 2019 for postpartum depression and showed lasting benefits, and certain contraceptive formulations like drospirenone have shown promise in easing premenstrual mood symptoms.
While this review doesn't provide all the answers — the authors note that a definitive direct link between hormone levels and depression still needs more research — it offers a useful big-picture view of how reproductive hormones and mood are connected throughout life.
Key findings
- PMDD affects approximately 5-8% of women and is linked to sensitivity to physiological changes in progesterone and allopregnanolone during the late luteal phase, rather than absolute hormone deficiency or excess
- A Danish nationwide cohort study of 1,061,997 women found a positive link between hormonal contraceptive use, especially progestin-containing contraceptives, and induced depression and antidepressant use, with the association strongest in adolescents
- The risk of depression during menopause transition is 2-5 fold greater than in late menopause, driven by day-to-day hormonal fluctuations rather than low estrogen levels per se
- Brexanolone (injectable allopregnanolone) showed superiority over placebo for postpartum depression in phase 3 trials, with 94% of responders having no relapse at 30 days, and was FDA-approved in March 2019
- Women with a history of postpartum depression had a 20-fold increased risk of developing postpartum depression again, and responded differently to abrupt sex hormone withdrawal
- Transdermal estradiol combined with intermittent micronized progesterone prevented depressive symptoms during menopausal transition (17% developed mood symptoms vs. 32% on placebo over 12 months)
Methods, briefly
Narrative review synthesizing evidence from epidemiological studies, randomized controlled trials, animal studies, and cohort studies examining the relationship between sex hormones and depression across the female lifespan. No systematic search protocol or meta-analytic methods described. References include studies with sample sizes ranging from 69 to over 1 million participants.
Limitations to keep in mind
- Narrative review without systematic search methodology, introducing potential selection bias in included studies
- No quality assessment of included studies was performed
- The review acknowledges that a direct causal link between sex hormone levels and depressive disorder has not been definitively established
- Much of the evidence on oral contraceptives and depression is observational, making it difficult to establish causation
- Limited discussion of confounding variables across the reviewed studies
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