What is the role of medroxyprogesterone (Progestin) in the management of Dysfunctional Uterine Bleeding (DUB)?

Medroxyprogesterone in Dysfunctional Uterine Bleeding

Medroxyprogesterone acetate is FDA-approved and effective for treating abnormal uterine bleeding due to hormonal imbalance, but levonorgestrel-releasing intrauterine devices are superior as first-line therapy, reducing menstrual blood loss by 71-95%. 1, 2

FDA-Approved Indications and Dosing

Medroxyprogesterone acetate is specifically indicated for abnormal uterine bleeding due to hormonal imbalance in the absence of organic pathology such as fibroids or uterine cancer. 1

For acute management of abnormal uterine bleeding:

• Administer 5-10 mg daily for 5-10 days, with 10 mg daily for 10 days being the optimal dose for inducing secretory transformation of adequately primed endometrium 1
• Progestin withdrawal bleeding typically occurs within 3-7 days after discontinuing therapy 1

For chronic/recurrent abnormal uterine bleeding:

• Begin on the calculated 16th or 21st day of the menstrual cycle 1
• Administer 5-10 mg daily for 5-10 days (10 mg for 10 days beginning on day 16 is optimal) 1
• Patients with recurrent episodes benefit from planned menstrual cycling with medroxyprogesterone 1

Comparative Effectiveness: Why MPA is Not First-Line

The levonorgestrel-releasing IUD (LNG-IUD) should be offered as first-line therapy before oral medroxyprogesterone because it reduces menstrual blood loss by 71-95% with efficacy comparable to endometrial ablation, far superior to the 20% reduction seen with oral progestogens. 2, 3, 4

Evidence hierarchy for treatment options:

• LNG-IUD (20 μg/day): 71-95% reduction in menstrual blood loss, most effective medical option 2, 3
• Oral progestogens (including medroxyprogesterone): Only 20% reduction in blood loss in ovulatory women, though more effective in anovulatory bleeding 4, 5
• Combined hormonal contraceptives: Effective for ovulatory dysfunction bleeding, can be combined with NSAIDs 3

Clinical Algorithm for Medroxyprogesterone Use

Step 1: Rule out contraindications

• Exclude pregnancy (β-hCG test mandatory in all reproductive-age women) 6, 3
• Exclude structural pathology via transvaginal ultrasound with Doppler 6
• Exclude endometrial hyperplasia/malignancy if risk factors present (age >45, obesity, diabetes, unopposed estrogen exposure) 6

Step 2: Determine bleeding pattern

• Anovulatory bleeding (irregular cycles, extremes of reproductive age, PCOS): Medroxyprogesterone 10 mg daily for 10 days each month for ≥3 months in adolescents; 5-10 mg for 10 days monthly for 6 months in reproductive-age women 7
• Ovulatory bleeding (regular cycles with heavy flow): Consider LNG-IUD first; if declined, medroxyprogesterone 5-10 mg daily from day 5-25 of cycle 5, 7

Step 3: Special populations requiring medroxyprogesterone consideration

• Cardiovascular disease/post-SCAD patients: LNG-IUD strongly preferred over oral hormones; avoid NSAIDs and tranexamic acid due to MI/thrombosis risk 3, 2
• Anticoagulation therapy: LNG-IUD reduces bleeding by 71-95% and is preferred due to minimal systemic absorption 2, 3
• Adolescents with anovulatory bleeding: Medroxyprogesterone 10 mg daily for 10 days monthly is appropriate first-line therapy 7

Critical Limitations and When to Escalate

Medroxyprogesterone has limited efficacy in ovulatory dysfunctional uterine bleeding, with only 20% reduction in blood loss compared to 50% with antifibrinolytics or 71-95% with LNG-IUD. 4, 2

Escalate care if:

• Bleeding saturates a large pad/tampon hourly for ≥4 hours (urgent evaluation needed) 6, 2
• Bleeding persists after 2-3 treatment cycles (perform hysteroscopy to exclude focal lesions missed by endometrial sampling) 3, 6
• Endometrial thickness >4 mm in postmenopausal women or any postmenopausal bleeding (refer to gynecology) 6
• Patient develops hemodynamic instability (consider high-dose estrogen or curettage) 7

Important Caveats

Medroxyprogesterone acetate is the only progestin with demonstrated full effectiveness in inducing secretory endometrium when used with full replacement estrogen doses, though micronized progesterone shows a superior cardiovascular safety profile. 8

Avoid estrogen therapy in anovulatory bleeding except for profuse bleeding unresponsive to progestin, as it increases endometrial hyperplasia and cancer risk. 9

Three out of 10 women with ovulatory DUB do not respond usefully to oral progestogens, necessitating alternative therapies such as NSAIDs, tranexamic acid, or LNG-IUD. 5