What is the recommended subcutaneous testosterone regimen, dosing, monitoring plan, and contraindications for women with hypoactive sexual desire disorder or other androgen‑deficiency symptoms after other causes have been excluded and non‑hormonal therapies have failed?

Subcutaneous Testosterone for Women with Hypoactive Sexual Desire Disorder

Direct Recommendation

Subcutaneous testosterone is not a first-line treatment for women with HSDD; transdermal testosterone (1% gel, 5g applied twice weekly) is the preferred androgen formulation when indicated, specifically for postmenopausal women after non-hormonal therapies have failed, with absolute contraindication in women with breast cancer or hormone-dependent malignancies. 1, 2

Patient Selection and Prerequisites

Before considering testosterone therapy, the following must be established:

• Confirmed postmenopausal status (testosterone is not recommended as first-line in premenopausal women) 1, 2
• Failure of FDA-approved first-line treatments: flibanserin (100 mg daily at bedtime) or bremelanotide (subcutaneous as needed) 1
• Failure of non-hormonal interventions: cognitive-behavioral therapy, pelvic physical therapy, vibrators/clitoral stimulatory devices 1, 2
• Adequate estrogen levels (testosterone may not be effective without sufficient circulating estrogen) 2
• No history of breast cancer or hormone-dependent malignancies (absolute contraindication) 2

Recommended Regimen

Formulation and Dosing

Transdermal testosterone is the preferred route, not subcutaneous:

• 1% testosterone gel, 5g applied twice weekly to dry, intact skin of abdomen, back, upper thighs, or upper arms 2
• Transdermal formulations avoid hepatic first-pass metabolism and are preferred over oral or injectable preparations 3
• Target testosterone levels in the mid-normal female range, not male reference ranges (avoid targeting 500-600 ng/dL) 2

Why Not Subcutaneous?

The evidence base and guideline recommendations consistently support transdermal (patch or gel) formulations rather than subcutaneous injections for women. 2, 3, 4 Subcutaneous testosterone is not mentioned in current guidelines as a standard route of administration for female HSDD.

Monitoring Plan

Baseline Assessment

• Total and free testosterone levels (can be measured at any time; peak occurs 6-8 hours post-gel application) 2
• Complete lipid profile 5
• Liver function tests 5
• Complete blood count 5

Follow-Up Schedule

• Every 3 months during the first year for laboratory monitoring 2, 5
• Assess for clinical improvement in sexual desire, arousal, and satisfaction 4
• Monitor for adverse effects (hirsutism, acne, voice changes) 4

Laboratory Targets

• Maintain testosterone levels in the mid-normal female range 2
• Continue monitoring lipid profiles, liver function, and blood counts at each visit 5

Absolute Contraindications

• Current or history of breast cancer 2
• Other hormone-dependent malignancies 2
• Current pregnancy or breastfeeding (general principle)
• Suspected breast cancer 2

Expected Efficacy

Modest benefit: Testosterone therapy results in approximately 1 additional satisfying sexual event every 2 months compared to placebo. 1, 2 This is similar to the efficacy of flibanserin, the FDA-approved first-line agent. 1

Common Adverse Effects

• Mild hirsutism (increased facial/body hair) 5, 4
• Acne (typically mild and reversible upon discontinuation) 5, 4
• Both side effects are generally well-tolerated and resolve within 2 months of stopping treatment 5

Treatment Duration and Reassessment

• Evaluate treatment effect after 3-6 months 6
• Consider limiting treatment to 24 months due to lack of long-term safety data 6
• If no clinical improvement after 6 months, discontinue therapy 6

Critical Pitfalls to Avoid

1. Do not use testosterone as first-line therapy: FDA-approved options (flibanserin, bremelanotide) and non-hormonal interventions should be tried first 1, 2

2. Do not prescribe to women trying to conceive: Exogenous testosterone suppresses spermatogenesis and may have long-term fertility impacts 6

3. Do not use in breast cancer survivors: Safety is not established and risk outweighs potential benefit 6, 2

4. Do not target male testosterone levels: Aim for mid-normal female range to minimize virilization 2

5. Do not use testosterone monotherapy without adequate estrogen: Efficacy may be compromised in hypoestrogenic states 2

6. Do not prescribe subcutaneous formulations: Evidence supports transdermal delivery, not subcutaneous injections 2, 3, 4

Treatment Algorithm

Step 1: Premenopausal women with HSDD → Flibanserin 100 mg daily at bedtime OR bremelanotide subcutaneous as needed 1

Step 2: If first-line fails or not tolerated → Off-label bupropion or buspirone 1

Step 3: Postmenopausal women with persistent HSDD after above failures → Consider transdermal testosterone 1% gel 5g twice weekly (if no contraindications) 2

Step 4: Monitor every 3 months for first year, reassess efficacy at 3-6 months, consider limiting to 24 months total 6, 2, 5