Practical Clinical Summary on Testosterone Therapy in Women

Practical Clinical Summary on Testosterone Therapy in Women (From ExcelMale.com)​

Based on the ExcelMale forum threads and related clinical literature, here's a comprehensive extraction of practical content for a clinical article:

Physiological Role & Rationale​

Key Functions:

• Testosterone serves dual roles: precursor for estrogen biosynthesis AND direct physiological effects via androgen receptors
• Critical for sexual function, bone health, mood, behavior, cognition, muscle strength, energy, and metabolic function
• Women produce approximately 1/12th the testosterone of men (average 4-7 mg/day in men vs. ~500 mcg/day in women)
• Over 80% of bioavailable testosterone in women comes from local intracrine production from adrenal precursors (androstenedione and DHEA)

Vaginal Health:

• Testosterone promotes pelvic blood flow, vascular smooth muscle relaxation, mucin secretion, and lubrication
• Modulates pain, inflammation, nerve fiber density, and neurotransmission in vaginal tissue
• Essential for maintaining vaginal tissue structure including smooth muscle thickness and collagen fiber compactness

Clinical Indications​

Evidence-Based:

• Hypoactive Sexual Desire Disorder (HSDD) in postmenopausal women (only FDA-recognized indication per Global Consensus Position Statement)
• Benefits include: improved sexual desire, arousal, orgasm, pleasure, and reduced sexual distress

Additional Applications (based on clinical experience):

• Menopausal symptom relief (energy, mood, vasomotor symptoms)
• Body composition improvement (increased lean mass, reduced fat)
• Bone mineral density maintenance
• Reduction of stress urinary incontinence
• May resolve menopausal symptoms even in women on aromatase inhibitors

Dosing Protocols​

Injectable Testosterone Cypionate (Subcutaneous):

• Starting dose: 2.5-5 mg twice weekly (total 5-10 mg/week)
• Normal production equivalent: ~500 mcg/day = 3.5 mg/week
• Practical range: 2.4-20 mg/week, though most women need 10-15 mg/week
• Evidence suggests mild supraphysiological levels (80-100 ng/dL) often needed for symptom resolution
• Adjust based on clinical response and side effects, not rigid blood level targets
• Use 27-gauge ½" insulin syringe for subcutaneous administration
• Steady state achieved in 6 weeks

Topical Testosterone:

• Compounded creams: 0.5-2 mg per day (typical dosing)
• Commercial men's products too strong; require compounding pharmacy
• Intravaginal application shows best absorption for creams
• Women's International Pharmacy (womensinternational.com) provides protocols and research packets

Testosterone Pellets:

• Doses: 50-225 mg (common US doses: 75, 100, 112.5, 125, 150 mg)
• Duration: 10-12 weeks
• Considerations: Cannot adjust if side effects develop; expensive; variable metabolism
• May provide more consistent levels but less flexible than injections

Monitoring:

• Initial assessment at 6 weeks post-initiation
• Measure total and free testosterone using LC-MS/MS (most accurate for low female ranges)
• Monitor Free Androgen Index (FAI) - aim to keep <5% per British Menopause Society
• Clinical response more important than specific target levels
• Check for androgen excess signs every 6 months

Target Levels & Individualization​

Blood Level Considerations:

• "Normal" female range not well-established and often insufficient for symptom resolution
• Clinical experience shows women tolerate total T levels 120-400 ng/dL
• Some women require levels above normal range for therapeutic benefit
• Individual variability is enormous: same 100 mg pellet dose produced 83-368 ng/dL range (4.4-fold difference)
• Dose based on response and side effects, not just serum levels
• Free testosterone levels more clinically relevant than total testosterone

Safety Profile​

Cardiovascular:

• Testosterone inversely associated with CVD risk in women
• Large database analysis showed DECREASED risk of major adverse cardiac events with testosterone therapy
• No increased risk of venous thromboembolism or pulmonary embolism
• Non-methylated testosterone has minimal effects on lipid profile (possible slight HDL decrease, not clinically significant)

Breast Cancer:

• 9-year retrospective study showed 35.5% REDUCTION in invasive breast cancer (144 vs. 223 per 100,000 person-years)
• Testosterone-androgen receptor complex is antiproliferative in breast tissue
• Testosterone downregulates estrogen receptor alpha and increases apoptosis in breast cancer cell lines
• May be protective, especially with subcutaneous testosterone pellet therapy
• Historically used as breast cancer treatment before pharmaceutical alternatives
• Safe in breast cancer survivors per multiple studies

Metabolic:

• No adverse effects on liver function (non-methylated forms)
• No changes in renal function or blood cell indices with transdermal testosterone
• May improve insulin sensitivity
• FTM transgender literature shows decades of high-dose use without increased morbidity/mortality

Other Safety Considerations:

• Does not stimulate endometrium
• No association with endometrial or other malignancies in published studies
• Blood pressure and metabolic parameters remain stable

Side Effects & Management​

Common Androgenic Side Effects:

1. Acne - tends to resolve with continued treatment (observed in FTM literature); 2.5 mg finasteride helpful (postmenopausal women only)
2. Facial/body hair growth - most common complaint; typically mild; manageable with shaving/laser; tolerance highly individual
3. Scalp hair thinning - genetics-dependent; some experience at low doses, others not at high doses; most concerning side effect
4. Clitoral enlargement - within reason, often leads to improved sexual response ("nuclear orgasms")
5. Voice deepening - rare at physiological doses; may be beneficial in male-dominated professions
6. Fine body hair at injection site - minimal, barely noticeable

Dose-Dependent:

• Virilization uncommon and reversible if caught early
• Voice changes and clitoral enlargement may become irreversible with prolonged exposure
• Using lowest effective dose minimizes androgenic effects

Vaginal Atrophy (Paradoxical Effect):

• High-dose or supraphysiological testosterone can cause vaginal atrophy
• Mechanism: testosterone suppresses estrogen, leading to tissue thinning, dryness
• Symptoms: dryness, irritation, bleeding, dyspareunia, increased UTI/BV risk
• More common in transgender men on masculinizing doses
• Treatment: local vaginal estrogen (cream, tablet, or ring) - does NOT interfere with systemic testosterone therapy
• Prevention: adequate lubrication during sexual activity; regular pelvic blood flow stimulation

Patient Selection:

• Avoid in women fearful of any cosmetic androgenic changes
• Set realistic expectations
• Behavioral changes not typically observed (pre-existing personality traits may intensify)

Formulation Considerations​

Advantages by Route:

• Subcutaneous injections: Inexpensive, effective, easy dose adjustment, steady-state in 6 weeks, no transference risk
• Creams: Convenient, no needles, adjustable dosing
• Pellets: Consistent levels, infrequent administration

Disadvantages:

• Injections: Requires self-injection (though with insulin needles, relatively painless)
• Creams: Variable absorption, transference risk to children/partners
• Pellets: Cannot reverse if sides develop, expensive, variable release, requires incision

Avoid:

• Oral 17-alpha-alkylated testosterone (hepatotoxicity risk)
• Products designed for men (dosing too high)

Barriers to Implementation​

Systemic Issues:

1. No FDA-approved testosterone products for women in US (Australia has Androphile for HSDD)
2. Not taught in medical schools
3. Residual fear from Women's Health Initiative study
4. Endocrine Society guidelines conservative/restrictive
5. Lack of physician awareness and training
6. Women must use off-label men's products or compounded formulations

Clinical Practice Challenges:

• Pharmacists may question prescriptions for females
• Insurance often won't cover
• Need for specialized compounding pharmacies
• Testing challenges (standard assays not sensitive enough for female ranges; need LC-MS/MS)

Best Practices & Recommendations​

Initiation:

1. Comprehensive clinical assessment
2. Rule out other causes of sexual dysfunction
3. Baseline testosterone and FAI measurement
4. Patient education on realistic expectations and side effects
5. Shared decision-making regarding route and dosing

Monitoring Protocol:

• Week 6: Check testosterone levels, assess symptoms, evaluate for androgen excess
• Every 6 months: Testosterone levels, clinical response assessment, side effect check
• Annual: Comprehensive metabolic panel, lipids, hematocrit

Combination Therapy:

• Often combined with estradiol in postmenopausal women
• Testosterone alone may resolve menopausal symptoms without estrogen in some women
• May require estrogen addition for optimal libido response (some women need both)

Special Populations:

• Premenopausal women: Limited data; careful consideration needed
• Breast cancer survivors: Appears safe; may be protective
• Women on aromatase inhibitors: May relieve symptoms without estrogen

Future Directions​

Needed:

• Medical school curriculum inclusion
• Professional society endorsement
• FDA-approved formulations for women
• Long-term safety studies
• Standardized diagnostic criteria for testosterone insufficiency
• Better laboratory reference ranges for women

Research Gaps:

• Optimal dosing strategies
• Long-term cardiovascular outcomes
• Breast cancer relationship clarification
• Cognitive and bone health effects
• Premenopausal indications

Key Takeaways for Clinicians​

1. Testosterone therapy in women has 80+ years of evidence supporting efficacy and safety
2. Mild supraphysiological levels often needed for symptom resolution
3. Individual response highly variable - treat the patient, not the lab value
4. Subcutaneous injections offer best balance of efficacy, safety, and cost
5. Androgenic side effects manageable and often well-tolerated
6. Cardiovascular and breast cancer data reassuring
7. Compounding pharmacies essential resource in absence of FDA-approved products
8. Patient selection and education critical to success

This comprehensive summary synthesizes the practical clinical information from the ExcelMale forum discussions and related medical literature, providing actionable guidance for clinicians considering testosterone therapy in women.