What is the starting regimen for a patient initiating Premarin (conjugated estrogens) oral and Provera (medroxyprogesterone) oral therapy?

Starting Regimen for Premarin and Provera Oral Therapy

For postmenopausal women with a uterus initiating hormone replacement therapy, start with Premarin (conjugated estrogens) 0.625 mg daily continuously, combined with Provera (medroxyprogesterone acetate) 10 mg daily for 12-14 consecutive days per month in a sequential regimen. 1

Specific Dosing Instructions

Premarin (Conjugated Estrogens)

• Start with 0.625 mg daily taken continuously (every day without interruption) 1
• This is the lowest effective dose for most postmenopausal women 1
• Can be taken at any time of day, but consistency is recommended 1

Provera (Medroxyprogesterone Acetate) - Sequential Regimen

• 10 mg daily for 12-14 consecutive days per month 1
• Two timing options are available:
  • Calendar day 1-14 of each month (continuous-sequential), OR
  • Calendar day 16-28 of each month (delayed-sequential) 1
• The 10 mg dose provides complete endometrial protection when combined with 0.625 mg conjugated estrogens 1

When to Start Therapy

• Blood pressure measurement is required before initiation 2
• No pelvic examination is required before starting unless clinically indicated 2
• Therapy can be started at any time if reasonably certain the patient is not pregnant 2, 1
• Rule out pregnancy if there is any uncertainty 1

Expected Bleeding Pattern

• Progestin withdrawal bleeding typically occurs 3-7 days after completing the 12-14 day Provera course 1
• This predictable monthly bleeding is expected and normal with sequential regimens 1
• If withdrawal bleeding does not occur within 3 weeks, advise pregnancy testing 2

Clinical Monitoring

• Re-evaluate at 3-6 month intervals to determine if treatment is still necessary and at the lowest effective dose 1
• Annual breast and pelvic examinations are recommended 1
• For undiagnosed persistent or recurrent abnormal vaginal bleeding, endometrial sampling should be undertaken before continuing therapy 1

Alternative Dosing Considerations

If 0.625 mg Premarin is Insufficient

• May increase to 1.25 mg daily if menopausal symptoms are not adequately controlled 1
• Continue the same Provera regimen (10 mg for 12-14 days) 1

If Withdrawal Bleeding is Undesired

• Consider continuous combined regimen: Premarin 0.625 mg daily plus Provera 2.5 mg daily (both taken every day without interruption) 3, 4
• This eliminates monthly withdrawal bleeding but may cause irregular spotting initially 4
• Amenorrhea is typically achieved within 6-15 months with continuous combined therapy 4

Important Safety Considerations

Contraindications - Do Not Start If Patient Has:

• Undiagnosed abnormal vaginal bleeding 1
• Current or history of breast cancer or estrogen-dependent neoplasia 1
• Active or history of venous thromboembolism (DVT, PE) 1
• Active or recent arterial thromboembolic disease (stroke, MI) 1
• Known liver dysfunction or disease 1
• Known or suspected pregnancy 1

Cardiovascular Risk

• Do not initiate in women with established coronary heart disease - the WHI study showed increased cardiovascular events in the first year of therapy 1, 5
• For women with cardiovascular risk factors, consider alternative progestins like micronized progesterone instead of medroxyprogesterone acetate 3, 6

Common Pitfalls to Avoid

• Do not use Provera alone without estrogen in postmenopausal women - this regimen is specifically for combined therapy 1
• Do not omit the progestin in women with a uterus - unopposed estrogen significantly increases endometrial cancer risk (32% hyperplasia rate at 3 years vs 3% with combined therapy) 1
• Do not start with higher doses - always begin at the lowest effective dose (0.625 mg Premarin) 1
• Do not continue indefinitely without reassessment - use the lowest dose for the shortest duration consistent with treatment goals 1

Patient Counseling Points

• Inform patients that breast tenderness, bloating, and mood changes may occur initially 1
• Weight gain is a common side effect reported with medroxyprogesterone acetate 7
• Advise patients to report immediately: new breast lumps, unusual vaginal bleeding, severe headaches, chest pain, leg pain/swelling, vision changes, or speech difficulties 1
• Emphasize that regular follow-up is essential for monitoring safety and efficacy 1