What is the recommended regimen for using Androgel (testosterone gel), Divigel (estradiol gel), and Utrogestan (progesterone) together in perimenopausal women?

Recommended Regimen for Androgel, Divigel, and Utrogestan in Perimenopause

For perimenopausal women, the recommended regimen is transdermal estradiol gel (Divigel) at 0.25-1.0 mg daily, micronized progesterone (Utrogestan) 200 mg daily for 12-14 days per month if the uterus is intact, and testosterone gel (Androgel) at the lowest effective dose only for specific symptoms not responding to other treatments. 1

Estradiol (Divigel) Administration

• Start with the lowest effective dose (0.25 mg delivering approximately 0.003 mg/day of estradiol) 2
• Apply to clean, dry skin, typically on the upper thigh or arm
• Can be titrated up to 1.0 mg daily based on symptom response 2
• Divigel has shown good tolerability with minimal skin irritation (only 1.7% discontinuation due to skin reactions) compared to patch formulations 3, 4

Progesterone (Utrogestan) Administration

• Required for women with an intact uterus to prevent endometrial hyperplasia 1
• Recommended dosage: 200 mg daily for the first 12-14 days of each month in a sequential regimen 4, 5
• Can be administered orally at bedtime to minimize side effects like drowsiness
• Alternative: continuous regimen of 100 mg daily if breakthrough bleeding is problematic

Testosterone (Androgel) Administration

• Should be used only for specific indications such as low libido not responding to estrogen/progesterone therapy
• Start at the lowest possible dose (typically 1/10th of the male dose)
• Apply to upper arms, shoulders, or thighs, rotating application sites
• Monitor for adverse effects: acne, hirsutism, voice changes, clitoromegaly

Important Clinical Considerations

Timing and Duration

• Initiate hormone therapy before age 60 or within 10 years of menopause for most favorable benefit-risk profile 1
• Use the lowest effective dose for the shortest duration needed to control symptoms 1
• Regular reassessment every 3-6 months to determine if treatment is still necessary 1

Contraindications

• Active liver disease
• Unexplained vaginal bleeding
• History of hormone-dependent cancers
• Recent history or active venous thromboembolism 1

Monitoring

• Initial follow-up 8-10 weeks after treatment initiation
• Annual comprehensive assessment of risks and benefits 1
• Monitor for breast tenderness, breakthrough bleeding, and skin reactions

Risks and Benefits

• Estrogen-progestin therapy increases risk of breast cancer, venous thromboembolism, stroke, and gallbladder disease 6
• Benefits include reduction in vasomotor symptoms, prevention of bone loss, and improvement in vaginal atrophy 6, 1
• Transdermal estrogen may have lower thrombotic risk than oral formulations

Special Considerations for Perimenopause

• Cyclic regimens are often preferred during perimenopause to mimic natural hormonal fluctuations
• Bleeding patterns may be irregular during initial months of therapy
• Consider adjusting dosage if breakthrough bleeding occurs
• If vasomotor symptoms are the primary concern, start with estrogen/progesterone before adding testosterone

Tapering and Discontinuation

• When discontinuing, consider gradual tapering rather than abrupt cessation
• Reduce estradiol dose by 50% every 2-4 weeks
• Monitor for return of symptoms during tapering process

This regimen should be adjusted based on symptom response and the development of any adverse effects, with the goal of using the lowest effective dose for the shortest necessary duration 1.