From the Guidelines
The next step in management for this 48-year-old female with elevated estrogen levels while on testosterone cream therapy would be to reduce the testosterone dose or discontinue the therapy temporarily, as testosterone can convert to estrogen through aromatization, particularly in women, which explains the elevated estrogen levels despite normal Pap smear and mammogram results. I recommend decreasing the current 2% testosterone cream dose by half or switching to a lower concentration (1%) applied to the same area less frequently, such as every other day instead of daily, as suggested by the principles of hormone replacement therapy 1. After 4-6 weeks on the adjusted regimen, estrogen levels should be retested to assess if they've normalized. If levels remain elevated despite dose reduction, complete discontinuation of testosterone therapy may be necessary, followed by consideration of alternative treatments for the original indication.
During this adjustment period, the patient should continue routine cancer screenings as scheduled, since prolonged elevated estrogen levels increase risk for estrogen-sensitive cancers, and a strict follow-up is fundamental in patients on treatment with hormone therapy, including promotion of breast self-examination and annual imaging from the age of 25 years onwards 1. The goal is to maintain therapeutic benefits of testosterone while minimizing conversion to estrogen, thereby reducing potential long-term risks associated with estrogen excess such as endometrial hyperplasia or breast tissue stimulation. It is also important to consider the use of combined estrogen and progestin patches, which can help to avoid an unopposed estrogen effect and maintain endometrial health in women with a uterus, as recommended in the guidelines for the assessment and management of female reproductive complications 1.
Key considerations in this case include:
- Monitoring estrogen levels after adjusting the testosterone dose
- Continuing routine cancer screenings
- Considering alternative treatments if testosterone therapy is discontinued
- Using combined estrogen and progestin patches to avoid an unopposed estrogen effect
- Adjusting the dose of hormone replacement therapy according to each woman's tolerance and feeling of wellbeing, as the dose of 17βE should be adjusted according to individual needs 1.
From the Research
Next Steps in Management
Given the elevated estrogen levels and normal Pap smear and mammogram results in a 48-year-old female on 2% testosterone cream therapy, the following steps can be considered:
- Monitoring of estrogen and testosterone levels to assess the effectiveness of the current therapy and potential need for adjustments 2
- Evaluation of symptoms related to hyperestrogenism, such as gynecomastia, and consideration of aromatase inhibitors or selective estrogen receptor modulators if necessary 3
- Assessment of the patient's menopausal status and consideration of hormone replacement therapy (HRT) for management of menopausal symptoms, if applicable 4
- Discussion of the potential risks and benefits of HRT in breast cancer survivors, if relevant, and consideration of alternative therapies for symptom management 5
Considerations for Testosterone Therapy
- The aim of testosterone replacement therapy is to improve symptoms and signs of testosterone deficiency, and the patient's response to 2% testosterone cream should be monitored 6
- The testosterone:estradiol ratio may be an important consideration in managing testosterone therapy, with a range of 10-30 potentially being beneficial 2
- Regular monitoring of liver function, lipid profiles, and hematocrit is recommended for patients on testosterone therapy 6