Transdermal Estradiol and Exercise in Mitigating Adverse Effects of Androgen Deprivation Therapy for Prostate Cancer Radiation Therapy
The goal of the clinical trial is to find out whether transdermal estradiol will reduce the adverse effects of androgen deprivation therapy in prostate cancer patients.

The primary aim of this study is to estimate the efficacy of transdermal estradiol (E2) in reducing androgen deprivation therapy induced adverse effects on sexual function. A secondary aim of this study is to estimate the utility of E2 and the combination of E2 with supervised exercise in reducing other androgen deprivation therapy related adverse effects.

Participants (n=310) will use transdermal estradiol for 12 months concomitant to androgen deprivation therapy. The use of transdermal estradiol will start at the beginning of the trial, at the same time as androgen deprivation therapy. A subgroup of participants (n=120) will also be allocated to perform six months supervised resistance training.

Researchers will compare transdermal estradiol group to control group, and resistance training groups and non-training control groups.
- EligibilityCriteria: Inclusion Criteria:  Men with localized prostate cancer, and scheduled for external beam radiation with adjuvant subcutaneous androgen deprivation therapy, leuprorelin (LHRH agonist) for at least 12 months without any other endocrinology treatments for prostate cancer Adults (age over 18 years) Sufficient performance status (Eastern Cooperative Oncology Group, 0-1) Body mass index between 18.5 - 30.0 Willingness to participate and signed consent  Exclusion Criteria:  Patients with low-risk prostate cancer (ISUP Gleason grade 1) Patients with expected adjuvant androgen deprivation therapy for less than one year Distant bone, lymph node, or soft tissue metastasis Cardiac pacemaker Prior recent cardiovascular event or stroke (<12 months) Past or current venous thromboembolism Other untreated or unstable malignancy in risk of recurrence/progression (as judged by the treating physician) Concurrent glucocorticoid treatment Physical disabilities for regular exercise Any medication or condition considered as a contraindication to estradiol (allergy to adjuvant compounds (carbomer, trolamine), history with thromboembolic disorders (protein C, protein S, or antithrombin deficiency), porphyria, acute or previous liver disease, drugs with cytochrome P450 enzyme metabolism (anticonvulsants: phenobarbital, phenytoin, carbamazepine; anti-infectives: rifampicin, rifapentine, nevirapine, efavirenz; and St. John's wort)) or leuprorelin (allergy to adjuvant compounds (polylactic acid), Qt-time prolonging drugs (quinidine, disopyramide, amiodarone, sotalol, dofetilide, ibutilide, methadone, moxifloxacin, antipsychotics) Known allergy to estradiol or leuprorelin Expected poor compliance or expected survival time of less than one year - HealthyVolunteers: No - Gender: Male - MinimumAge: 18 Years - StdAgeList: Adult, Older Adult