When is progesterone (a hormone) necessary?

When Progesterone Therapy is Necessary

Progesterone therapy is necessary for women with a uterus who are taking estrogen therapy to prevent endometrial hyperplasia and reduce the risk of endometrial cancer, for women with secondary amenorrhea due to progesterone deficiency, and for pregnant women with a history of spontaneous preterm birth to reduce recurrence risk. 1, 2

Endometrial Protection in Hormone Therapy

For Postmenopausal Women

• Progesterone is essential when estrogen is prescribed to women with an intact uterus 1, 2
  • Without progesterone, estrogen alone increases risk of endometrial hyperplasia and cancer
  • Clinical studies show 64% of women on estrogen-only therapy develop endometrial hyperplasia within 36 months versus only 6% when progesterone is added 2

Dosing for Endometrial Protection

• For postmenopausal women taking estrogen: 200 mg oral progesterone daily at bedtime for 12 continuous days per 28-day cycle 2
• Alternative regimens may include transdermal preparations with various estrogen/progesterone combinations 3

Menstrual Disorders

Secondary Amenorrhea

• Indicated for women with secondary amenorrhea due to progesterone deficiency 2
• Dosing: 400 mg oral progesterone at bedtime for 10 days 2
• Efficacy: 80% of women experience withdrawal bleeding within 7 days of completing treatment 2

Abnormal Uterine Bleeding

• Used to regulate intermenstrual bleeding and decrease heavy menstrual bleeding in reproductive-age and perimenopausal women 4
• Helps establish regular withdrawal bleeding patterns in women with anovulatory cycles 5

Preterm Birth Prevention

For Women with Prior Spontaneous Preterm Birth

• 17-alpha-hydroxyprogesterone caproate (17P) 250 mg IM weekly from 16-20 weeks until 36 weeks gestation is recommended for singleton pregnancies with history of spontaneous preterm birth 1
• Evidence shows 34% reduction in recurrent preterm birth with this regimen 1

For Women with Short Cervix

• Vaginal progesterone (90 mg gel or 200 mg suppository daily) is recommended for singleton pregnancies without prior preterm birth but with cervical length ≤20 mm at 24 weeks 1

Transgender Healthcare

For Transgender Women

• Progesterone is often combined with estradiol therapy and anti-androgens for feminization 3
• Helps achieve hormonal balance and may contribute to breast development
• Must be monitored for cardiovascular risks, particularly thromboembolism 3

Fertility and Early Pregnancy Support

Assisted Reproduction

• Luteal phase support with progesterone is critical following in-vitro fertilization 6
• Commonly used in intrauterine insemination cycles 6

Important Clinical Considerations

Safety Profile

• Natural (micronized) progesterone has a better safety profile than synthetic progestins 7, 5
  • Lower risk of breast cancer (RR: 1.08 for estrogen with progesterone vs. higher risk with synthetic progestins) 7
  • No negative impact on HDL/LDL cholesterol ratio 7
  • No significant effects on carbohydrate metabolism, blood pressure, or body weight 7

Administration Timing

• Oral progesterone should be taken at bedtime due to potential drowsiness and dizziness 2, 5
• Some women may experience blurred vision, difficulty speaking or walking after taking progesterone 2

Contraindications

• Known or suspected pregnancy
• Undiagnosed vaginal bleeding
• Active thromboembolic disorders or history of arterial thrombotic disease
• Current or history of hormone-dependent cancers
• Liver problems
• Peanut allergy (for formulations containing peanut oil) 2

When Progesterone is NOT Indicated

• Multiple gestations (no evidence of effectiveness) 1
• Preterm labor (no evidence of effectiveness for primary tocolysis) 1
• Preterm premature rupture of membranes 1
• Singleton pregnancies without prior preterm birth and normal cervical length 1

Progesterone therapy should be prescribed with careful consideration of the patient's medical history, particularly regarding thromboembolic risk, and should be monitored regularly for efficacy and side effects.