Is a high estrogen level of 400, with a follicle-stimulating hormone (FSH) level of 5.6, considered normal in a 54-year-old premenopausal female with regular menstrual cycles, who is undergoing testosterone replacement therapy (TRT) with a testosterone level of 203, and has recently started Tirzepatide (a glucagon-like peptide-1 (GLP-1) receptor agonist) for weight loss?

From the Research

The high estrogen level of 400 pg/mL is not normal for a 54-year-old premenopausal woman and warrants further investigation, especially given her age and recent testosterone replacement therapy. Normal estrogen levels for premenopausal women typically range from 30-400 pg/mL, but vary widely throughout the menstrual cycle. Her level is at the upper limit, which combined with her age and testosterone therapy raises concerns. The testosterone replacement therapy could be contributing to the elevated estrogen, as testosterone can convert to estrogen through aromatization, particularly in adipose tissue, as noted in the context of hormone therapy for menopausal symptoms 1. Her obesity is also a significant factor, as fat tissue produces estrogen. Although she has lost weight with tirzepatide (which is positive), the elevated estrogen level should be monitored closely.

Some key points to consider in her management include:

• The potential for testosterone therapy to influence estrogen levels, as discussed in the context of menopausal hormone therapy 2
• The importance of monitoring for signs of estrogen excess and considering adjustments to her testosterone dose or the addition of an aromatase inhibitor if high estrogen levels persist, in line with recommendations for the management of menopausal symptoms 3
• The need for comprehensive assessment and monitoring, including repeat hormone levels and possibly an endometrial biopsy, to rule out conditions such as endometrial hyperplasia, as suggested by guidelines for menopausal hormone therapy 4

Given the most recent and highest quality evidence, I recommend additional testing to determine the cause of the elevated estrogen level, including repeat hormone levels at different points in her menstrual cycle, and possibly an endometrial biopsy to rule out endometrial hyperplasia, as part of a comprehensive approach to managing her symptoms and minimizing risks associated with high estrogen levels, in accordance with the principles outlined in the latest guidelines on menopausal hormone therapy 2.