Hop Extract Versus Soy Isoflavone Extract for Menopausal Symptoms (HOPES)

HOPES (Hops On Psychological and Estrogenic Symptoms in Menopause) is a randomized, double-blind, active-controlled nutritional intervention study in 120 peri- and postmenopausal women aged 45 to 60 years with moderate to severe menopausal symptoms. For 12 weeks, participants take one capsule per day of either a full spectrum hop (Humulus lupulus L.) extract or a soy isoflavone extract. Both products are marketed dietary supplements, and there is no placebo arm. The main question is whether the hop extract, which combines prenylated flavonoids with bitter acids, improves the psychological symptoms of menopause (depressive mood, irritability, anxiety, and physical and mental exhaustion) more than the soy extract. The main outcome is the change in the psychological subscale of the Menopause Rating Scale (MRS) from baseline to week 12. Secondary outcomes include the other MRS domains, anxiety, depressive symptoms, menopause-related quality of life, body composition, and safety.

Inclusion Criteria: * Woman aged 45 to 60 years (both inclusive). * Perimenopausal or postmenopausal status according to the Stages of Reproductive Aging Workshop +10 (STRAW+10) criteria. * Moderate to severe menopausal symptoms, defined as a total Menopause Rating Scale (MRS) score of 15 or higher at the baseline assessment prior to randomization. * Not receiving menopausal hormone therapy (MHT) and not having received it in the previous 3 months. * Ability to understand and complete the study questionnaires autonomously. * Written informed consent. Exclusion Criteria: * Known allergy or hypersensitivity to soy or any of its derivatives. * Known allergy or hypersensitivity to hops or to other species of the Cannabaceae family. * Personal history of breast cancer, endometrial cancer or any other hormone-dependent tumor. * Genital bleeding of undiagnosed cause. * Current use, or use in the previous 3 months, of MHT, tibolone, selective estrogen receptor modulators, or dietary supplements or products specifically intended for menopausal symptoms or with a relevant phytoestrogen content, or anticipated need to start any of them during the study. * Current treatment with antidepressants, anxiolytics, hypnotics, gabapentin or pregabalin. * Known liver disease or abnormal baseline liver profile (transaminases more than twice the upper limit of normal). * Moderate or severe renal insufficiency. * History of venous thromboembolic disease. * Oral anticoagulant treatment. * Body mass index (BMI) of 35 kg/m2 or higher. * Pacemaker or any other implantable electronic device (contraindication for bioimpedance). * Unstabilized major psychiatric disorder. * Risky alcohol consumption or substance dependence. * Simultaneous participation in another clinical trial or intervention study, or participation in one within the previous 30 days. * Pregnancy or lactation.