Will testosterone replacement therapy affect a left ovarian cyst in a woman with low serum testosterone (<10 ng/dL) and appropriate symptoms?

Testosterone Therapy and Ovarian Cysts: Safety and Management

Testosterone replacement therapy can be safely initiated in a patient with a simple ovarian cyst, as benign ovarian cysts do not contraindicate testosterone treatment and available evidence suggests testosterone does not cause malignant transformation of benign ovarian lesions.

Initial Ovarian Cyst Characterization

Before initiating testosterone therapy, the ovarian cyst must be properly characterized:

• Transvaginal ultrasound is essential to determine if the cyst is simple (benign) versus complex or solid 1
• Simple cysts in premenopausal women are functional in 98.7% of cases and resolve spontaneously 1
• Characteristic benign features include: simple cyst appearance, hemorrhagic cyst with spiderweb pattern, endometriomas with low-level echoes, or dermoid features 1
• If the cyst has concerning features (solid components, irregular borders, increased vascularity), further evaluation with MRI or surgical consultation is warranted before starting any hormonal therapy 1

Evidence on Testosterone and Ovarian Tissue

The available data on testosterone's effects on ovarian tissue is reassuring:

• A large multicenter study of 85 transmasculine persons on testosterone (average duration 36 months) found entirely benign ovarian histopathology at oophorectomy 2
• In this cohort, 49.4% had simple/follicular cysts, 5.9% had polycystic changes, and 38.8% had normal pathology—all benign findings 2
• No association was found between duration of testosterone therapy and presence of ovarian cysts 2
• One case report documented a serous borderline tumor in a transgender adolescent on testosterone, but this represents an extremely rare occurrence and causation was not established 3

Testosterone Replacement Protocol

For this patient with testosterone <10 ng/dL and appropriate symptoms:

• Confirm hypogonadism with a second morning total testosterone level between 8-10 AM, as guidelines recommend two separate measurements showing levels <300 ng/dL 1
• Measure free testosterone by equilibrium dialysis and sex hormone-binding globulin, as these are often low in patients with obesity and provide more accurate assessment 1
• Check luteinizing hormone and follicle-stimulating hormone to distinguish primary from secondary hypogonadism 1

Testosterone formulation options:

• Transdermal preparations (gel or patch) are preferred as first-line therapy, delivering 50-100 μg daily with stable serum levels 1
• Intramuscular injections are an alternative if cost is prohibitive or patient preference dictates, though they cause fluctuating levels 1
• Target testosterone levels to the middle tertile of normal range (450-600 ng/dL) to minimize adverse effects while achieving symptom relief 1

Monitoring Requirements

Initial monitoring (first 2-3 months):

• Measure serum testosterone levels 2-3 months after treatment initiation to confirm therapeutic range 1
• Assess hematocrit at baseline and follow-up, as testosterone increases red blood cell production 1
• Evaluate symptom improvement including energy, libido, and other presenting complaints 1

Ongoing surveillance:

• Repeat pelvic ultrasound at 6-12 months to document cyst stability or resolution (this is prudent given the baseline finding, though not specifically mandated by testosterone guidelines)
• Annual clinical review assessing compliance, symptoms, and any adverse effects 1
• Annual testosterone and hematocrit measurements once stable 1
• No routine additional monitoring tests are required unless specific symptoms develop 1

Critical Contraindications and Cautions

Absolute contraindications to testosterone therapy:

• If the patient is attempting to conceive, testosterone must not be prescribed as it suppresses spermatogenesis and causes oligospermia/azoospermia 1
• Breast cancer or other hormone-sensitive malignancies 1
• Recent cardiovascular event within 3-6 months 1

Relative considerations:

• Cardiovascular risk should be discussed, though recent large randomized trials show testosterone does not increase myocardial infarction or stroke risk 1, 4
• Polycythemia risk requires hematocrit monitoring 1
• Avoid 17-alpha-alkylated oral testosterone due to hepatotoxicity 1

Key Clinical Pitfalls

• Do not assume all low testosterone requires treatment—symptoms must be present and attributable to hypogonadism 1
• Do not use a single testosterone measurement for diagnosis; two morning samples are required 1
• Do not overlook that obesity itself lowers testosterone through decreased sex hormone-binding globulin 1
• Lifestyle modifications including weight loss should be counseled concurrently, as they can increase testosterone levels independently 1
• Do not prescribe testosterone if fertility is desired in the near term 1

The presence of a simple ovarian cyst does not preclude testosterone therapy, but proper characterization of the cyst and baseline documentation are essential before initiating treatment.