What are the guidelines for using esterified estrogens/methyltestosterone for treating post-menopausal symptoms?

Guidelines on the Use of Esterified Estrogens/Methyltestosterone for Post-Menopausal Symptoms

Esterified estrogens/methyltestosterone should only be used for moderate to severe vasomotor symptoms associated with menopause that have not improved with estrogen therapy alone, and should be used at the lowest effective dose for the shortest possible time due to significant safety concerns. 1

FDA-Approved Indications

• Esterified estrogens/methyltestosterone is indicated specifically for the treatment of moderate to severe vasomotor symptoms associated with menopause in patients not improved by estrogens alone 1
• There is no evidence that this combination is effective for nervous symptoms or depression without associated vasomotor symptoms, and it should not be used to treat such conditions 1
• The combination is available in regular strength (Estratest) and half-strength (Estratest HS) formulations 2

Safety Concerns and Contraindications

• Esterified estrogens/methyltestosterone is contraindicated in women with:

  • Unusual vaginal bleeding 1
  • Current or history of certain cancers, especially breast or uterine cancer 1
  • History of stroke or heart attack in the past year 1
  • Current or history of blood clots 1
  • Current or history of liver problems 1
  • Known hypersensitivity to any components of the medication 1

• Serious potential adverse effects include:

  • Breast cancer 1
  • Cancer of the uterus 1
  • Stroke and heart attack 1
  • Blood clots 1
  • Dementia 1
  • Gallbladder disease 1
  • Ovarian cancer 1

Position of Major Guidelines

• The U.S. Preventive Services Task Force recommends against the use of hormone therapy (including combinations with androgens) for the primary prevention of chronic conditions in postmenopausal women 3, 4
• Current guidelines emphasize that hormone therapy should be used primarily for symptom management rather than prevention of chronic conditions 5
• The American College of Obstetricians and Gynecologists recommends caution in using hormone therapy solely to prevent osteoporosis and suggests that alternative therapies should be considered 3
• For women with an intact uterus requiring hormone therapy, guidelines typically recommend estrogen plus progestin rather than estrogen plus androgen combinations 5

Evidence for Efficacy

• Clinical studies have shown that esterified estrogens/methyltestosterone can effectively treat vasomotor symptoms 6
• The combination has been shown to increase circulating levels of bioavailable testosterone and suppress sex hormone-binding globulin (SHBG), which may explain improvements in sexual functioning compared to estrogen alone 6
• In a study of surgically menopausal women, the combination therapy was associated with significant improvement in somatic symptoms (hot flashes, vaginal dryness, and insomnia) 7
• The combination may increase vertebral bone mineral density compared to pre-treatment values 7

Monitoring and Management

• Women taking esterified estrogens/methyltestosterone should:
  • Have regular follow-up with their healthcare provider every 3-6 months to reassess the need for continued therapy 1
  • Undergo breast examinations and mammograms as recommended by their healthcare provider 1
  • Be monitored for signs of androgen excess such as acne, alopecia, and hirsutism 2
  • Be evaluated for cardiovascular risk factors 1

Common Pitfalls to Avoid

• Using esterified estrogens/methyltestosterone for indications other than moderate to severe vasomotor symptoms not relieved by estrogen alone 1
• Prescribing this combination for primary prevention of chronic conditions like osteoporosis or cardiovascular disease 3, 4
• Failing to consider alternative therapies with potentially better safety profiles for menopausal symptom management 5
• Not monitoring for adverse effects related to both the estrogen component (e.g., thromboembolic events) and the androgen component (e.g., virilization) 2

Algorithm for Decision-Making

1. Confirm moderate to severe vasomotor symptoms that significantly impact quality of life 1
2. Try estrogen-only therapy first for symptom management 1
3. If estrogen alone is ineffective, consider esterified estrogens/methyltestosterone only if:
   • Patient has no contraindications 1
   • Patient understands risks and benefits 1
   • Lower-risk alternatives have been considered 5
4. Use the lowest effective dose for the shortest possible time 1
5. Regularly reassess the need for continued therapy every 3-6 months 1
6. Discontinue if adverse effects occur or if symptoms resolve 1

In conclusion, while esterified estrogens/methyltestosterone can be effective for treating moderate to severe vasomotor symptoms unresponsive to estrogen alone, its use should be limited due to safety concerns, and patients should be carefully selected and monitored.