RecruitingPhase 3ACTRN12624000475549

A randomised double-blinded interventional trial of Estradiol and Zoloft to treat Menopausal Depression

A randomised double-blinded interventional trial of the efficacy of Estradiol and Zoloft in treating Menopausal Depression

Sponsor

Monash University

Enrollment

120 participants

Start Date

Jun 22, 2025

Study Type

Interventional

Conditions

Menopause Depression

Summary

Depressive symptoms are prevalent among middle-aged women, especially during the menopausal transition. However, the impact of menopause on depression is often overlooked, leading to inadequate treatment and poor outcomes. While current guidelines recommend traditional antidepressants as first-line management, the evidence for hormonal therapy is limited. To address this gap, we propose a new clinical trial comparing the efficacy of Menopause Hormone Therapy and antidepressants in treating menopausal depression. Given that menopausal depression most likely stems from hormonal fluctuations, it is hypothesised that hormonal treatments are more appropriate than antidepressants.

Eligibility

Sex: FemalesMin Age: 45 YearssMax Age: 60 Yearss

Inclusion Criteria10

i. Females who are currently physically well
ii. 45 – 60 years of age
iii. Current DSM-5 diagnosis of depression disorder
iv. MENO-D score > 20
v. Able to give informed consent
vi. Menopausal as determined by standardised classification guidelines for female reproductive aging (Stages of Reproductive – STRAW)
vii. First-onset or relapse of depression during menopause
viii. Evidence of a normal mammogram in the preceding 24 months
ix. Documented normal Pap smear and pelvic examination in the preceding two years
x. English language proficiency (to provide informed consent and complete cognitive test battery)

Exclusion Criteria8

i. Patients with known abnormalities in the hypothalamic-pituitary gonadal axis, thyroid dysfunction, central nervous system tumours, active or past history of a venous thromboembolic event, breast pathology, undiagnosed vaginal bleeding, or abnormal Pap smear results.
ii. Patients with any significant unstable medical illness such as epilepsy and diabetes or known active cardiac, renal, or liver disease; or the presence of illness causing immobilisation.
iii. Patients experiencing severe melancholia, neurovegetative symptoms or current suicidality necessitating acute hospitalisation or intensive psychiatric treatment.
iv. Patients whose depressive illness is directly related to illicit substance use
v. Patients with psychotic symptoms or past history of severe mental illness including schizophrenia, and bipolar disorder.
vi. Pregnancy / Lactation
vii. Smoking > 10 cigarettes per day, >3 standard drinks of alcohol per day, illicit drug use.
viii. Planned changes to psychotropic medication or psychotherapy regimen.

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Interventions

50mcg estradiol transdermal patch applied twice a week and 100mg prometrium oral tablet taken daily (both for 12 weeks in total) Adherence will be assessed at each visit with participant reporting nu

50mcg estradiol transdermal patch applied twice a week and 100mg prometrium oral tablet taken daily (both for 12 weeks in total) Adherence will be assessed at each visit with participant reporting number of pills left