What are sample topical estrogen and testosterone therapy regimens for females?

Sample Topical Estrogen and Testosterone Therapy Regimens for Females

Topical Estrogen Therapy

For postmenopausal women with vaginal atrophy symptoms, low-dose vaginal estrogen is the most effective first-line hormonal treatment, with multiple formulation options available. 1, 2

Vaginal Estrogen Formulations and Dosing

Estradiol vaginal cream:

• 0.003% estradiol cream (15 μg estradiol in 0.5 g cream): Apply daily for 2 weeks, then twice weekly for maintenance 2
• Alternative: 0.625 mg conjugated equine estrogens per 1 g vaginal cream, applied once daily 3

Estradiol vaginal tablets:

• 10 μg estradiol tablets: Insert daily for 2 weeks, then twice weekly for maintenance 1, 2

Estradiol vaginal ring:

• Estradiol-releasing vaginal ring: Replace every 3 months; provides simplest regimen with longest duration between changes 1, 2
• One study used a ring releasing 50 μg of 17β-estradiol daily 1

Transdermal estradiol gel (for systemic symptoms, not vaginal-only):

• 0.1% estradiol gel: 0.25 mg, 0.5 mg, or 1.0 mg daily (delivering 0.003 mg, 0.009 mg, or 0.027 mg estradiol daily, respectively) 4
• Applied to skin for vasomotor symptoms and systemic effects 4

Transdermal estradiol patches (for systemic hormone replacement):

• Patches releasing 50-100 μg of 17β-estradiol daily: Change twice weekly or weekly depending on brand 1, 5
• For women with intact uterus: Add progestogen (micronized progesterone 200 mg daily or medroxyprogesterone acetate 10 mg daily) for 12-14 days every 28 days 1
• For women without uterus: Estrogen-only patches can be used continuously without progestogen 2, 5

Key Clinical Considerations for Estrogen Therapy

Women without a uterus do not require progestogen addition, making estrogen-only therapy appropriate and having a more favorable risk/benefit profile 2, 5

For women with an intact uterus using vaginal estrogen, higher-dose preparations may require progestogen to prevent endometrial hyperplasia, though low-dose vaginal estrogen typically does not 2

Topical vaginal estrogen has minimal systemic absorption with no concerning safety signals for stroke, venous thromboembolism, invasive breast cancer, colorectal cancer, or endometrial cancer in large studies 1, 2

Contraindications include:

• History of hormone-sensitive breast cancer (absolute contraindication) 1, 2, 6
• Active or history of deep vein thrombosis or pulmonary embolism 6
• Active viral hepatitis or severe liver disease 6
• Ischemic heart disease 6

For breast cancer survivors with severe symptoms unresponsive to non-hormonal measures, low-dose vaginal estrogen can be considered only after thorough discussion of risks and benefits 1, 2

Estriol-containing preparations may be preferable for women on aromatase inhibitors because estriol is less potent and cannot be converted to estradiol 2, 5

Topical Testosterone Therapy

Intravaginal testosterone cream has been shown to improve vaginal atrophy and sexual function in postmenopausal women, though it is not FDA-approved for this indication. 1, 7

Testosterone Formulations and Dosing

Intravaginal testosterone cream:

• Applied three times weekly for 12 weeks in clinical trials 7
• One study in breast cancer survivors on aromatase inhibitors found intravaginal testosterone cream was safe and improved vaginal atrophy and sexual function 1
• Specific dosing: The exact concentration used in studies varies, but testosterone cream applied vaginally three times weekly showed significant improvement in vaginal trophism after 12 weeks 7

Evidence for Testosterone Efficacy

After 12 weeks of treatment with topical testosterone compared with placebo lubricant:

• Increased percentage of participants had vaginal pH less than 5 7
• Increased vaginal health score 7
• Increased number of lactobacilli 7
• Significant improvement in vaginal trophism 7

Vaginal androgens (DHEA/prasterone) can also be considered for vaginal dryness or pain with sexual activity, though this is technically a DHEA preparation rather than pure testosterone 1

Important Caveats for Testosterone Therapy

Safety data for androgen-based therapy in survivors of hormonally mediated cancers are limited 1

The FDA label for prasterone (DHEA) warns that exogenous estrogens are contraindicated in women with a history of breast cancer, and similar caution should apply to testosterone preparations 1

Testosterone therapy for vaginal atrophy is off-label use, as it is not FDA-approved for this indication 7

Treatment Algorithm

First-line (non-hormonal):

• Vaginal lubricants for sexual activity 2
• Vaginal moisturizers applied 3-5 times weekly 2

Second-line (if first-line insufficient):

• Low-dose vaginal estrogen (cream, tablets, or ring) as detailed above 2
• Consider intravaginal testosterone cream three times weekly if estrogen is contraindicated or patient prefers alternative 7

For women requiring systemic hormone replacement:

• Transdermal 17β-estradiol patches (50-100 μg daily) as first choice 1, 5
• Add micronized progesterone if uterus intact 1, 5