Risks Associated with Excessive Progesterone Intake

Cardiovascular and Thromboembolic Events

In postmenopausal women taking estrogen plus progestin, there are 9 additional strokes per 10,000 woman-years, 12 additional DVTs per 10,000 woman-years, and 9 additional pulmonary emboli per 10,000 woman-years compared to placebo, with elevated risks in older women (>65 years) and those with obesity or factor V Leiden 1

Estrogen plus progestin increases invasive breast cancer by 8 cases per 10,000 woman-years after 11 years of follow-up in the WHI trial, with risk increases with longer duration of therapy and in women with prior oral contraceptive use or smoking history 1

Gallbladder disease increases by 20 cases per 10,000 woman-years with estrogen plus progestin 1
Probable dementia increases by 22 cases per 10,000 woman-years in women >65 years 1
Urinary incontinence increases by 872 cases per 10,000 woman-years 1

In preterm birth prevention, excessive doses of 17P show no benefit: 250 mg IM weekly in twin gestations provides no reduction in preterm birth or perinatal morbidity 2, 3

The minimum effective dose for endometrial protection is 2.5 mg medroxyprogesterone acetate daily continuously or 10 mg daily for 12-14 days per month, according to the American College of Obstetricians and Gynecologists 4
Micronized progesterone 200 mg orally or vaginally provides equivalent endometrial protection, as recommended by the American College of Obstetricians and Gynecologists 5, 4

The US Preventive Services Task Force concludes that harmful effects of estrogen and progestin likely exceed chronic disease prevention benefits in most postmenopausal women 6
Women >65 years have higher relative risk of stroke, breast cancer, and dementia with combined therapy, as reported by the American College of Cardiology 1, 6

The Centers for Disease Control and Prevention recommends that progesterone-containing contraceptives carry specific cardiovascular warnings for women with multiple arterial cardiovascular risk factors, with a Category 2-3 risk depending on formulation 7
The Centers for Disease Control and Prevention also recommends that women with severe hypertension have a Category 2-3 risk, with DMPA carrying higher risk than other progestin-only methods 7
Women with vascular disease have a Category 2-3 risk across progestin formulations, according to the Centers for Disease Control and Prevention 7
Limited evidence suggests that women with hypertension using progestin-only pills or injectables have a small increased risk for cardiovascular events, as reported by the Centers for Disease Control and Prevention 7

The American College of Obstetricians and Gynecologists states that using progesterone in multiple gestations exposes patients to risks without benefit, with multiple RCTs showing no effect on preterm birth rates or perinatal morbidity/mortality 8, 9, 10
The American College of Obstetricians and Gynecologists also recommends that progesterone should not be used as primary tocolysis in active preterm labor, due to insufficient evidence 8, 9
Progesterone has no effect on delivery interval, gestational age at delivery, or neonatal outcomes in preterm premature rupture of membranes, according to the American College of Obstetricians and Gynecologists 8, 9, 10

The Centers for Disease Control and Prevention recommends that breastfeeding women less than 1 month postpartum have a Category 2 risk due to theoretical concerns about progestin exposure effects on the developing neonatal brain, though direct evidence shows no significant negative effects 7