What are the side effects of Androgen Deprivation Therapy (ADT) plus apalutamide?

Medical Advisory BoardAll articles are reviewed for accuracy by our Medical Advisory Board
Educational purpose only • Exercise caution as content is pending human review
Article Review Status
Submitted
Under Review
Approved

Last updated: June 8, 2025View editorial policy

Personalize

Help us tailor your experience

Which best describes you? Your choice helps us use language that's most understandable for you.

From the Guidelines

Androgen Deprivation Therapy (ADT) plus apalutamide can cause several side effects, including hot flashes, fatigue, joint pain, and decreased sexual function, as well as more serious side effects such as cardiovascular problems, bone density loss, and metabolic changes, with apalutamide specifically causing rash, falls, fractures, hypothyroidism, and seizures in rare cases, as reported in the TITAN study 1.

Common Side Effects

  • Hot flashes
  • Fatigue
  • Joint pain
  • Decreased sexual function

Serious Side Effects

  • Cardiovascular problems, such as heart attacks and strokes
  • Bone density loss leading to osteoporosis and fractures
  • Metabolic changes, including weight gain, increased cholesterol levels, and insulin resistance that may lead to diabetes
  • Cognitive changes
  • Mood disturbances, including depression
  • Muscle loss

Apalutamide-Specific Side Effects

  • Rash
  • Falls
  • Fractures
  • Hypothyroidism
  • Seizures (in rare cases)
  • Decreased appetite
  • Diarrhea
  • Hypertension These side effects occur because both ADT and apalutamide work by blocking testosterone and other male hormones that cancer cells need to grow, but these hormones also have important functions throughout the body, as discussed in the initial management of noncastrate advanced, recurrent, or metastatic prostate cancer guideline update 1. Regular monitoring with your healthcare provider is essential during treatment, including bone density scans, lipid panels, blood pressure checks, and assessments for cardiovascular risk, as recommended in the advanced prostate cancer guideline part I 1. Exercise, proper nutrition, and bone-strengthening medications may help manage some of these side effects.

From the FDA Drug Label

Of patients treated with ERLEADA (n=1073), Grade 3–4 adverse reactions occurred in 39% of patients younger than 65 years, 41% of patients 65–74 years, and 49% of patients 75 years or older Falls in patients receiving ERLEADA with androgen deprivation therapy was elevated in the elderly, occurring in 8% of patients younger than 65 years, 10% of patients 65–74 years, and 19% of patients 75 years or older.

The side effects of Androgen Deprivation Therapy (ADT) plus apalutamide include:

  • Grade 3-4 adverse reactions in 39% to 49% of patients, depending on age
  • Falls, particularly in the elderly, occurring in 8% to 19% of patients, depending on age 2

From the Research

Side Effects of ADT plus Apalutamide

The combination of Androgen Deprivation Therapy (ADT) and apalutamide is a treatment approach for prostate cancer. While the specific side effects of this combination are not extensively detailed in the provided studies, the individual components' side effects can be considered:

  • ADT Side Effects:
    • Vasomotor flushing, loss of libido and impotence, fatigue, gynaecomastia, anaemia, osteoporosis, and metabolic complications 3, 4, 5
    • Decreases in bone mineral density, metabolic changes, decreased libido and sexual dysfunction, hot flashes, gynecomastia, reduced testicle size, anemia, and fatigue 4
  • Management of ADT Side Effects:
    • Gabapentin for hot flashes 3
    • Exercise programs for fatigue, sexual function, and cognitive function 3
    • Denosumab for bone loss 3, 4
    • Metformin for metabolic changes 3
    • Toremifene for lipid profile improvement 3
    • Intermittent ADT for reducing early side effects 3, 5
  • Apalutamide and ADT Combination:
    • The combination of apalutamide with ADT has been studied for its efficacy in biochemically recurrent prostate cancer 6
    • While the study does not extensively detail the side effects of the combination, it mentions that the health-related quality of life (HRQoL) was similar in patients treated with apalutamide alone, ADT alone, or their combination 6

Considerations for Treatment

It's essential to weigh the benefits and risks of ADT plus apalutamide, considering the potential side effects and the individual patient's health status. Management strategies for ADT side effects, as mentioned above, can be applied to mitigate treatment-related morbidity 3, 4, 5.

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

Have a follow-up question?

Our Medical A.I. is used by practicing medical doctors at top research institutions around the world. Ask any follow up question and get world-class guideline-backed answers instantly.