What is the role of progesterone in treating vaginal bleeding?

Progesterone for Vaginal Bleeding

The role of progesterone in treating vaginal bleeding depends critically on the clinical context: it is highly effective for abnormal uterine bleeding in reproductive-age and perimenopausal women, particularly when administered as a levonorgestrel intrauterine device (reducing menstrual blood loss by 71-95%), but has no role in early pregnancy bleeding except in women with recurrent miscarriages. 1

For Non-Pregnant Women with Abnormal Uterine Bleeding

First-Line Treatment Options

The levonorgestrel-releasing intrauterine device (LNG-IUD, 20 μg/day) is the most effective progesterone-based treatment for heavy menstrual bleeding, reducing blood loss by 71-95%. 1, 2 This represents the gold standard among progesterone therapies and has efficacy comparable to endometrial ablation. 1

For women who cannot or will not use an LNG-IUD:

• Oral progesterone 200 mg daily for 21 days per month effectively reduces menstrual blood loss in women with cyclic heavy bleeding. 1, 2
• Vaginal micronized progesterone (400 mg twice daily from day 14 for 12 days) significantly reduces bleeding intensity and duration in premenopausal women with dysfunctional uterine bleeding. 3
• For women experiencing breakthrough bleeding on progesterone-only pills, adding 5 mg norethisterone acetate significantly reduces bleeding frequency and quantity at 2,4, and 6 weeks. 4

Special Clinical Scenarios

For women on antiplatelet or anticoagulation therapy who develop abnormal uterine bleeding, the LNG-IUD is particularly effective and should be the preferred option. 1 This addresses bleeding while maintaining necessary cardiovascular protection.

In perimenopausal women with endometrial hyperplasia and heavy bleeding, initiate LNG-IUD (20 μg/day) for optimal bleeding control and potential regression of non-atypical hyperplasia. 2 If medical treatment fails, proceed to hysteroscopy to evaluate for focal lesions, then consider endometrial ablation or hysterectomy rather than prolonged medical management. 2

Treatment Algorithm for Dysfunctional Uterine Bleeding

1. Rule out pregnancy, structural causes (fibroids, polyps), and malignancy before attributing bleeding to hormonal imbalance. 1
2. For women with heavy menstrual bleeding and desire for contraception, place LNG-IUD as first-line therapy. 1
3. For women declining IUD or requiring oral therapy, prescribe oral progesterone 200 mg daily for 21 days per month. 1, 2
4. If bleeding persists after 3-6 months or is unacceptable to the patient, perform endometrial biopsy to exclude hyperplasia or malignancy, then consider alternative treatments. 1, 2

Important Caveats

NSAIDs (5-7 days during menstruation) can be used adjunctively to reduce bleeding volume and should be considered before escalating progesterone doses. 1 However, avoid NSAIDs in women with cardiovascular disease or thrombotic risk. 1

Tranexamic acid during menstruation is highly effective for reducing menstrual blood loss but should be avoided in women with cardiovascular disease or thrombotic risk. 1

For Pregnant Women with Early Pregnancy Bleeding

Progesterone therapy does NOT significantly increase live birth rates in unselected women with early pregnancy bleeding (75% vs 72% with placebo, p=0.08). 5 However, a critical subgroup effect exists.

When to Use Progesterone in Pregnancy

Prescribe vaginal micronized progesterone 400 mg twice daily in women with early pregnancy bleeding who have a history of three or more previous miscarriages (72% live birth vs 57% with placebo; relative rate 1.28, p=0.004). 5

Consider progesterone in women with early pregnancy bleeding and one or two previous miscarriages based on shared decision-making (76% vs 72% with placebo; relative rate 1.05, p=0.07). 5

Do NOT routinely prescribe progesterone for early pregnancy bleeding in women with no previous miscarriages (74% vs 75% with placebo; relative rate 0.99, p=0.72). 5

When NOT to Use Progesterone in Pregnancy

Vaginal progesterone has NO role in preventing preterm birth in women with short cervix and no history of spontaneous preterm birth—use it only for cervical length ≤20 mm diagnosed before 24 weeks. 6 This is a completely different indication than early pregnancy bleeding.

For Postmenopausal Women on Estrogen Therapy

Progesterone is essential for endometrial protection in postmenopausal women with a uterus taking estrogen therapy. 7 The standard regimen is progesterone 200 mg daily for 12 continuous days per 28-day cycle in combination with continuous estrogen. 7

Vaginal progesterone gel (Crinone 4%, 45 mg daily) from days 1-10 of each month with continuous estrogen produces predictable withdrawal bleeding in 91.9% of women, while twice-weekly administration with continuous estrogen maintains amenorrhea in 80.6% of women. 8 Both regimens effectively prevent endometrial hyperplasia. 8

Contraindications and Safety

Do NOT prescribe progesterone in women with: 7

• Known or suspected pregnancy (when treating non-pregnancy bleeding)
• Peanut allergy (oral progesterone capsules contain peanut oil)
• Current or history of thromboembolism
• Undiagnosed vaginal bleeding (must evaluate first)
• Active liver disease
• Known or suspected breast or uterine cancer

Common but less serious side effects include headaches, breast pain, irregular bleeding/spotting, abdominal cramping, nausea, and vaginal yeast infection. 7 These do not require discontinuation unless intolerable.

Serious side effects requiring immediate evaluation include stroke, heart attack, pulmonary embolism, sudden severe headache, chest pain, leg pain with swelling, or vision changes. 7

Progesterone Has NO Role In:

• Uterine fibroid-related bleeding as primary therapy (oral contraceptives or GnRH agonists are preferred; LNG-IUD superior if contraception desired). 6
• Acute hemorrhagic bleeding requiring immediate hemostasis (requires different interventions).
• Bleeding from structural lesions (fibroids, polyps, malignancy) without addressing the underlying pathology. 1