Hormonal fluctuations significantly impact women's mental health and may contribute to conditions such as premenstrual dysphoric disorder, postnatal depression, and menopausal depression. Recently, a research team conducted a thorough review examining the role of estrogen and progesterone in treating these disorders, highlighting both established and emerging therapeutic approaches; their findings were published in Frontiers in Pharmacology.
Premenstrual dysphoric disorder (PMDD) affects approximately 3.2% of women of reproductive age. While hormone levels remain within normal ranges, affected women exhibit heightened sensitivity to fluctuations, particularly in allopregnanolone (ALLO), a metabolite of progesterone that influences GABA-A receptor activity. Treatments include selective serotonin reuptake inhibitors and combined oral contraceptives, with formulations such as drospirenone/ethinylestradiol and newer options like nomegestrol acetate/17β-estradiol showing promise. For severe cases, gonadotropin-releasing hormone analogues suppress ovarian hormone fluctuations but require add-back therapy to mitigate side effects.
Postnatal depression (PND), which affects up to 17.22% of new mothers globally, is linked to a sharp postpartum drop in estrogen and ALLO, which disrupts neurochemical stability. Symptoms range from mood disturbances to severe anxiety and suicidal ideation. Brexanolone, a synthetic ALLO, provides rapid symptom relief within 60 hours by modulating GABA-A receptors. Zuranolone, an oral alternative, offers a more accessible option but remains costly. Transdermal estradiol has also been explored for PND, particularly in combination with progesterone.
Menopausal depression results from declining estrogen levels, affecting serotonergic and dopaminergic neurotransmission and leading to mood instability, cognitive changes, and increased anxiety. Up to 40% of women experience depressive symptoms during menopause. Investigators highlighted in their review that menopause hormone therapy with transdermal estrogen has proven effective for symptom reduction in this patient population. Selective estrogen receptor modulators, such as raloxifene and bazedoxifene, have also shown neuroprotective potential. Tibolone, a synthetic steroid, has demonstrated benefits in mood stabilization and cognitive function, while testosterone therapy is under investigation, though evidence of its benefit remains inconclusive.
The authors underscored the need for personalized treatment for patients with these mood disorders, as hormonal sensitivity varies widely among individuals. While hormone therapy presents a promising avenue for managing these conditions, long-term safety data and larger-scale trials are essential to refine protocols.
"Gonadal hormone therapies offer promising options for managing PMDD, PND, and menopausal depression by addressing hormonal imbalances that contribute to mood fluctuations," wrote lead author Eveline Mu, PhD, of the Department of Psychiatry, HER Centre Australia, Monash University, and colleagues.
The authors reported no conflicts of interest.