What are the contraindications for estrogen and testosterone (hormone) therapies?

Contraindications for Estrogen and Testosterone Hormone Therapies

Both estrogen and testosterone therapies have specific contraindications that must be carefully considered before initiating treatment to avoid serious adverse outcomes.

Estrogen Therapy Contraindications

Absolute Contraindications

• Hormone-dependent cancers 1:

  • Breast cancer (active or history)
  • Low-grade serous epithelial ovarian cancer
  • Granulosa cell tumors
  • Endometrioid uterine adenocarcinoma (advanced)
  • Certain types of sarcoma (leiomyosarcoma and stromal sarcoma)

• Other absolute contraindications:

  • Undiagnosed abnormal genital bleeding 1
  • Active thromboembolic disorders 1
  • Pregnancy 2

Relative Contraindications

• History of venous thromboembolism (VTE) 3
• Active cardiovascular or cerebrovascular disease 4
• Severe liver disease 2

Testosterone Therapy Contraindications

Absolute Contraindications

• Carcinoma of the breast 5
• Known or suspected carcinoma of the prostate 5
• Pregnancy (contraindicated in women; risk of fetal virilization) 5
• Men seeking fertility (suppresses spermatogenesis) 2

Relative Contraindications

• Severe lower urinary tract symptoms (LUTS) 2
• Polycythemia (elevated hematocrit) 5
• Obstructive sleep apnea (untreated) 2
• Active cardiovascular disease 2

Special Considerations for Estrogen Therapy

Cancer Survivors

• For cancer survivors with premature ovarian insufficiency (POI), estrogen therapy should be carefully evaluated 2:
  • Transdermal 17β-estradiol is preferred for cancer survivors due to lower cardiovascular risk 2
  • Oral estrogens should be avoided in patients with liver dysfunction or elevated thrombotic risk 2

Route of Administration Considerations

• Transdermal estrogen has lower risk of VTE and stroke compared to oral formulations 2, 1
• Vaginal estrogen for genitourinary symptoms has minimal systemic absorption and may be safer in some cases where systemic therapy is contraindicated 1

Special Considerations for Testosterone Therapy

Monitoring Requirements

• Before initiating testosterone therapy:

  • Evaluate for prostate cancer 5
  • Check baseline hematocrit 5
  • Assess cardiovascular risk factors 2

• During testosterone therapy:

  • Monitor hematocrit at 3-6 months after starting treatment, then annually 5
  • Monitor for worsening of BPH symptoms 5
  • Evaluate PSA levels in men at risk for prostate cancer 2

Secondary Exposure Risks

• Risk of virilization in children and women through skin contact with testosterone gel 5
• Requires strict adherence to application protocols:
  • Apply only to upper arms/shoulders
  • Cover application sites with clothing
  • Wash hands thoroughly after application
  • Avoid skin-to-skin contact with others

Combined Hormone Therapy Risks

• Combined estrogen and testosterone therapy in postmenopausal women is associated with significantly increased risk of invasive breast cancer compared to estrogen-only therapy 6
• Risk increases by approximately 17.2% per year of combined use 6

Decision Algorithm for Hormone Therapy

1. Assess indication for therapy:

   • For estrogen: Menopausal symptoms, POI, genitourinary symptoms
   • For testosterone: Male hypogonadism with confirmed low testosterone levels

2. Screen for absolute contraindications:

   • If any absolute contraindication exists, do not prescribe
   • Consider alternative non-hormonal treatments

3. Evaluate relative contraindications and risk factors:

   • Age and time since menopause (for estrogen)
   • Cardiovascular risk profile
   • Cancer risk factors
   • Thrombotic risk factors

4. Select appropriate formulation and route:

   • For estrogen: Transdermal preferred for those with cardiovascular risk
   • For testosterone: Consider gel, injection, or other formulations based on patient factors

5. Establish monitoring protocol:

   • Regular follow-up for efficacy and adverse effects
   • Laboratory monitoring as indicated

Common Pitfalls to Avoid

• Prescribing testosterone to eugonadal men - Strong evidence against this practice 2
• Overlooking fertility concerns - Testosterone therapy suppresses spermatogenesis 2
• Inadequate monitoring - Failure to monitor hematocrit can lead to polycythemia 5
• Inappropriate estrogen use in hormone-sensitive cancers - Can stimulate cancer growth 1
• Ignoring route of administration - Transdermal estrogen has lower VTE risk than oral 2

By carefully evaluating contraindications and selecting appropriate patients for hormone therapy, clinicians can maximize benefits while minimizing risks of adverse outcomes.