Hormone Therapy and Depression: What to Know and How to Cope

Hormone therapy can affect mood, and some people may notice depressive symptoms or mood swings while on treatment, although this does not happen to everyone. Mood changes, including anxiety or depression, have been reported as possible side effects depending on the type of hormone and individual risk factors. ^[1] Patient guidance for common hormone treatments lists mood swings and irritability among expected side effects, and dose or type adjustments may help. ^{[2] [3]}

How hormones can influence mood

• Estrogen fluctuations: Rapid drops or unstable estrogen levels can be linked to mood symptoms, especially during perimenopause. Depression risk can rise when estrogen levels are significantly reduced, with sleep problems, prior depression, and stress increasing vulnerability. ^{[4] [5] [6]}
• Progestins and mood: Some progesterone or progestin products list mood swings and irritability as common adverse reactions. ^[3]
• Testosterone changes: In men, low testosterone or testosterone-suppressing therapy (androgen deprivation) is associated with higher rates of depression, though benefits of replacement therapy for depression remain uncertain and individualized. [PM8]
• Cancer-related hormone therapies: For prostate cancer, mood changes such as anxiety and depression can occur with hormone therapy. ^[1]

How common is it?

The exact frequency varies by therapy and population. Many people do not develop depression with hormone therapy, but mood shifts can occur, and certain life factors (poor sleep, prior depression, stress) raise the chance. ^[4] In general patient guidance, mood swings are recognized as a side effect that may improve with adjustments to dose or formulation. ^[2]

Does estrogen help or worsen mood?

It can be both, depending on context:

• When estrogen is fluctuating (perimenopause), carefully selected estradiol therapy has shown antidepressant effects in some randomized trials, especially in women with recent stress or vasomotor symptoms (hot flashes). [PM29] [PM30] [PM19] [PM20]
• Estrogen is not a first‑line antidepressant, and evidence for combined estrogen‑progestin effects on mood is mixed and less certain. [PM19] [PM20]

Red flags: when to call your clinician

• Persistent low mood, hopelessness, loss of interest, marked fatigue, sleep or appetite changes, or thoughts of self‑harm are reasons to seek prompt care. ^[7]
• Any unusual vaginal bleeding during hormone therapy should be reported quickly. ^{[2] [3]}

Practical coping steps

• Talk to your prescriber before changing anything. Adjusting dose, route (oral vs transdermal), or switching products may reduce mood side effects. ^[2]
• Screen and monitor: If you’ve had depression or anxiety before, let your clinician know; closer monitoring is advised when mood issues are a known risk. ^[7]
• Prioritize sleep: Poor sleep amplifies mood symptoms; treat insomnia and manage hot flashes to improve rest. Interrupted sleep is a known contributor to depression risk during hormonal changes. ^[4]
• Lifestyle supports: Regular physical activity, structured routines, social connection, and stress management can help reduce depressive symptoms. [PM22]
• Evidence‑based therapies: For clinically significant depression, antidepressants and psychotherapy are front‑line treatments, with hormone therapy considered adjunctive in select perimenopausal cases. [PM19] [PM20] [PM18]
• Manage vasomotor symptoms: In perimenopause, addressing hot flashes and night sweats may improve mood; estradiol can help some women with both vasomotor and mood symptoms. [PM19] [PM20] [PM29]
• Safety planning: If you notice rapid mood decline after starting a new hormone, contact your clinician; some products list mood swings as common adverse reactions and warrant reassessment. ^{[3] [2]}

Special situations

• Prostate cancer hormone therapy: Expect possible mood changes; proactive mental health support and exercise programs can help resilience. Depression and anxiety are recognized side effects in this setting. ^[1]
• Diabetes and women’s health: Women have higher depression rates, and hormonal milestones (menstruation, pregnancy, postpartum, menopause) can raise risk, so screening is helpful if you also manage diabetes. ^[8]

Bottom line

Hormone therapy can influence mood, and a subset of people may experience depressive symptoms or mood swings. Most people will not develop clinical depression, but being aware of risk factors, monitoring symptoms, and using proven treatments (therapy, medications) alongside careful hormone adjustments can make a big difference. ^{[4] [2]} [PM19] [PM20]