Editing Hormonal Therapy (section)

== Prevention & Management of Complications on ADT (2021 CUA Guidelines§) ==

=== Cardiometabolic ===

* '''Lifestyle changes (smoking cessation, dietary modifications, exercise)'''
** Patients should be encouraged to attend supervised exercise programs using a combination of resistance and aerobic training
*** Supervised exercise therapy in men with PCa is superior to self-implemented exercise regimens
*** '''Benefits of exercise in males on ADT (10)'''
**** '''Physical domains (5):'''
****# '''Prevention of muscle loss and resultant decline in lean body mass'''
****# '''Decreased body mass index'''
****# '''Improved muscle strength'''
****# '''Improvements in peak oxygen consumption and endothelial function'''
****# '''Improved overall physical function'''
**** '''Functional domains (2):'''
****# '''Lower levels of fatigue'''
****# '''Decreased risk of falls and fractures'''
**** '''Endocrine domains (2):'''
****# '''Improved insulin and glucose homeostasis'''
****# '''Improved in lipid profile'''
**** '''Multiple health-related quality of life domains'''
* '''Monitor blood pressure and treat hypertension''' for a target of <130/80
* '''Diabetes screening and lipid profile (see above) assessments should be continued at 6–12 month-intervals throughout treatment duration'''
** Dyslipidemia should be treated according to current best practice guidelines

=== Bone health ===

* '''Lifestyle changes'''
** '''Smoking and alcohol cessation'''
*** Smoking and alcohol use are associated with bone loss and fractures
** '''Exercise therapy''' using a combination of resistance and aerobic training, preferably in a supervised setting
*** Exercise may preserve BMD in men receiving ADT
* '''Calcium intake (1200 mg daily total from diet and supplements) and vitamin D supplementation (800–2000 IU daily)'''
** No evidence that shows this decreases risk of BMD loss or fractures in men receiving ADT but have been shown to prevent fractures in the general population age > 50
* '''Pharmacotherapy'''
** See Bone Health section in Castrate-Resistant Prostate Cancer Chapter Notes
** '''Bisphosphonates (zoledronic acid, alendronate, and pamidronate) can increase bone mineral density in men on ADT'''
** '''Indications for pharmacotherapy (4):'''
**# '''Osteoporosis'''
**# '''History of fragility fractures in the hip or spine'''
**# '''History of multiple fragility fractures'''
**# '''Moderate or high 10-year fracture risk'''
*** '''Other guideline-based indications for pharmacotherapy'''
**** '''2019 CUA CRPC Guidelines recommend denosumab or zoledronic acid every 4 weeks, along with daily calcium and vitamin D in men with CRPC and bone metastases'''
**** '''2020 CUA CSPC Guidelines recommend that all men treated with ADT require vitamin D supplementation (800-1200IU daily) and calcium supplementation (800mg-1000mg total intake daily). Those at high risk of fractures should be treated with bone targeted therapy (zoledronic acid 5mg once a year, alendronate 70mg weekly, denosumab 60mg every 6 months).'''
* '''Surveillance DXA (until treatment cessation)'''
** '''Every 2–3 years in low 10-year fracture risk'''
** '''Every 1-2 years in'''
*** '''Osteopenia'''
*** '''Moderate or high risk for fractures'''
** '''Patients started on pharmacological therapy should have followup DXA to assess for treatment response.'''

=== Hot flashes ===

* '''Lifestyle changes'''
** '''Avoidance of potential patient-identified triggers, commonly heat or spicy foods'''
* '''Pharmacological (5) (none are Health Canada-approved for hot flashes):'''
*# '''Medroxyprogesterone acetate (Provera)''' 20 mg orally daily
*# '''Megestrol acetate (Megace)''' 20 mg orally twice daily
*# '''Cyproterone acetate (Androcur)''' 50–100 mg orally daily
*# '''Gabapentin (Neurontin)''' 900 mg orally daily
*# '''Venlafaxine (Effexor)''' 75 mg orally daily
** Few case reports describe progression of prostate cancer with megestrol acetate; therefore, monitoring of disease is important
** The best pharmacological therapy to treat hot flashes remains unclear
*** '''Randomized trial comparing medical therapy for hot flashes'''
**** Population: 311 males with prostate cancer treated with ADT and experiencing hot flashes
**** Randomized to venlafaxine, medroxyprogesterone acetate, or cyproterone acetate
**** Primary outcome: change in median daily hot-flush score between randomization and 1 month
**** Results:
***** '''Decreases in hot-flush score were significantly larger in the cyproterone and medroxyprogesterone groups than in the venlafaxine group'''
**** Irani, Jacques, et al."Efficacy of venlafaxine, medroxyprogesterone acetate, and cyproterone acetate for the treatment of vasomotor hot flushes in men taking gonadotropin-releasing hormone analogues for prostate cancer: a double-blind, randomised trial." The lancet oncology 11.2 (2010): 147-154.
* '''Intermittent ADT improves hot flashes and should be considered in appropriately selected patients'''
* '''Acupuncture may have a beneficial effect and can be considered in patients unwilling or unable to use pharmacotherapy.'''

=== Breast events ===

* '''Options (3):'''
*# '''Tamoxifen (selective estrogen receptor modulator)'''
*#* Effective for prophylaxis and treatment of breast events
*# '''Radiation therapy (10 Gy)'''
*#* Effective for prophylaxis of both gynecomastia and mastodynia and treatment of mastodynia; '''radiation has no benefit once gynecomastia has begun'''
*# '''Surgical''' (select patients with gynecomastia)
** '''Prophylaxis for the prevention of gynecomastia in men receiving ADT is not currently recommended'''
** '''Tamoxifen is more effective than''' a single 12-Gy fraction of '''RT for prophylaxis and treatment of breast events'''

=== Cognitive function ===

* '''Monitor for cognitive decline and depression throughout duration of treatment'''

=== Fatigue ===

* '''Best treated with exercise therapy'''

=== Anemia ===

* '''Mild in most cases and often does not warrant treatment.'''
* '''Reversible after stopping ADT, but may take up to 1 year'''
* '''Indications for hematology referral (2):'''
*# '''Severe anemia'''
*# '''Decline in hemoglobin that exceeds the expected response to ADT alone'''

=== Sexual function and body image ===

* '''Consider referral to a sex therapist in males desiring improved sexual function'''
* Erectile dysfunction may be treated with various interventions, including phosphodiesterase inhibitors; however, treatment efficacy may be poor without adequate mental and physical arousal
* Treatment for loss of libido in males on ADT is difficult
* '''Intermittent ADT may improve libido and erectile function and should be considered in appropriately selected patients'''

=== Health related quality of life ===

* '''Exercise therapy should be encouraged to improve HRQOL during treatment'''
* '''Intermittent ADT improves HRQOL and should be considered in appropriately selected patients.'''
** In general, men with non-metastatic PCa are likely to benefit from intermittent ADT without major concern for compromised oncological outcomes, while those with metastatic PCa should be considered for intermittent therapy with caution.