What is the appropriate intramuscular testosterone cypionate dosing schedule, monitoring parameters, and contraindications for a woman being treated for hypoactive sexual desire disorder or menopausal symptoms due to documented low serum testosterone?

Testosterone Cypionate Dosing for Women via Intramuscular Injection

Standard Dosing Regimen

For women with hypoactive sexual desire disorder (HSDD) or menopausal symptoms due to documented low testosterone, testosterone cypionate 100 mg intramuscularly once monthly is the evidence-based dosing regimen. 1

This monthly dosing schedule was studied specifically in both pre- and postmenopausal women with HSDD and demonstrated significant improvement in sexual desire scores compared to baseline. 1

Clinical Context and Indications

• Testosterone therapy for women is indicated only for HSDD in postmenopausal women according to the most comprehensive meta-analyses and clinical practice guidelines. 2
• The diagnosis requires both documented low serum testosterone levels and the presence of distressing symptoms of low sexual desire that are not attributable to other medical, psychiatric, or relationship factors. 2
• Women with premature ovarian insufficiency (POI) may be considered for androgen treatment, though the supporting data are limited and long-term health effects remain unclear. 3

Monitoring Protocol

Initial Assessment (Before Starting Therapy)

• Obtain baseline morning total testosterone using an accurate assay (ideally LC-MS/MS). 4
• Measure free testosterone by equilibrium dialysis if total testosterone is borderline or if the patient has conditions affecting SHBG (obesity, liver disease). 4
• Document baseline hematocrit/hemoglobin, lipid profile, and liver function tests. 4
• Screen for contraindications including active breast cancer, cardiovascular disease within the past 3–6 months, and untreated severe liver disease. 3, 4

Follow-Up Monitoring

• At 3–6 months after initiation: Assess clinical response (improvement in sexual desire and distress), measure testosterone levels, and check hematocrit, lipid profile, and liver enzymes. 3
• If treatment effect is not evident by 3–6 months, discontinue therapy. 3
• Consider limiting treatment duration to 24 months given the lack of long-term safety data in women. 3
• Once stable and effective, monitor testosterone levels and safety parameters (hematocrit, lipids, liver function) every 6–12 months. 4

Expected Outcomes

• Women receiving 100 mg testosterone cypionate monthly demonstrated significant increases in sexual desire scores compared to baseline, even in those with normal baseline testosterone levels. 1
• The improvement in sexual function is modest but clinically meaningful, with increases in satisfying sexual episodes and decreases in distress related to low desire. 5
• Testosterone therapy has little to no effect on energy, mood, or physical function in women, similar to findings in men. 4

Alternative Formulations and Comparative Efficacy

• Transdermal testosterone patches (300 mcg/day) are FDA-studied in postmenopausal women not on estrogen therapy and showed modest but meaningful improvement in sexual function at 24 weeks. 5
• The transdermal patch delivering 300 mcg/day resulted in an increase of 2.1 satisfying sexual episodes per 4 weeks compared to 0.7 with placebo (P<0.001). 5
• Injectable testosterone cypionate offers the advantage of monthly dosing and no risk of transfer to partners or children, unlike topical preparations. 6, 7
• Subcutaneous administration (50–150 mg weekly) is an effective and well-tolerated alternative to intramuscular injection in transgender patients and may be extrapolated to cisgender women, though specific dosing studies in women with HSDD are lacking. 8, 9

Safety Considerations and Contraindications

Absolute Contraindications

• Active or treated breast cancer (HRT is generally contraindicated in breast cancer survivors). 3
• Recent cardiovascular events (myocardial infarction or stroke within 3–6 months). 4
• Pregnancy or active desire for fertility (testosterone can cause virilization of a female fetus). 4
• Hematocrit >54% or untreated polycythemia. 4

Relative Contraindications and Precautions

• Severe liver disease (use free testosterone index for diagnosis if cirrhosis is present). 4
• Untreated severe obstructive sleep apnea. 4
• Hypertension is not a contraindication; transdermal estradiol is preferred for estrogen replacement in hypertensive women with POI, but testosterone can be used with appropriate monitoring. 3

Androgenic Adverse Effects

• Unwanted hair growth (hirsutism) is the most common androgenic side effect, occurring in approximately 30% of women receiving 300 mcg/day transdermal testosterone. 5
• Acne, voice deepening, and clitoral enlargement are dose-dependent and may be irreversible if therapy is continued at high doses. 5
• Monitor for virilizing effects at each visit and reduce dose or discontinue if these occur. 3

Breast Cancer Risk

• Four cases of breast cancer were diagnosed among women receiving testosterone in one large trial (vs. none in placebo), though one was diagnosed within 4 months and another had pre-existing symptoms. 5
• The long-term effects of testosterone on breast cancer risk remain uncertain and require ongoing surveillance. 5
• Women with POI should be informed that HRT (estrogen-based) has not been found to increase breast cancer risk before the age of natural menopause, but testosterone data are limited. 3

Practical Administration Details

• Injection site: Deep intramuscular injection into the gluteal muscle (for administration by a healthcare provider) or anterolateral thigh (for self-injection). 6, 7
• Needle specifications: Use an 18-gauge needle to draw testosterone from the vial and a 21–23 gauge, 1–1.5 inch needle for intramuscular injection. 6
• Volume: 100 mg testosterone cypionate is typically supplied as 1 mL of a 100 mg/mL concentration or 0.5 mL of a 200 mg/mL concentration. 7
• Supplies to prescribe: Syringes (1–3 mL), drawing needles (18-gauge), injection needles (21–23 gauge, 1–1.5 inch), alcohol prep pads, gauze, adhesive bandages, and a sharps disposal container. 6

Dose Adjustment Strategy

• If clinical response is inadequate at 3–6 months and testosterone levels remain low-normal, consider increasing the dose or shortening the interval (e.g., 100 mg every 3 weeks). 3, 7
• If virilizing side effects occur, reduce the dose by 50% or discontinue therapy. 3
• If hematocrit rises above the reference range, temporarily withhold therapy, reduce the dose, or perform phlebotomy. 7
• Target testosterone levels in the mid-to-upper normal female range (specific targets for women are not well-defined in guidelines, but levels should not exceed the lower limit of the normal male range). 4

Critical Pitfalls to Avoid

• Do not prescribe testosterone for women without documented HSDD or low testosterone levels; symptoms alone are insufficient. 2
• Do not continue therapy beyond 24 months without reassessing the risk-benefit ratio, as long-term safety data in women are lacking. 3
• Do not use testosterone in women actively seeking pregnancy or who have not completed childbearing without thorough counseling on teratogenic risks. 4
• Do not ignore androgenic side effects; virilization can be irreversible if therapy is continued at high doses. 5
• Do not assume testosterone will improve energy, mood, or physical function in women, as evidence for these benefits is minimal. 4