# Conjugated estrogens/medroxyprogesterone acetate

Conjugated estrogens/medroxyprogesterone acetate (CEs/MPA), sold under the brand names Prempro and Premphase, is a combination product of conjugated equine estrogens (Premarin), an estrogen collected from horse urine, and medroxyprogesterone acetate (Provera), a progestogen, which is used in menopausal hormone therapy for the treatment of menopausal symptoms.
In 2018, it was the 308th most commonly prescribed medication in the United States, with more than 1 million prescriptions.
vte Results of the Women's Health Initiative (WHI) menopausal hormone therapy randomized controlled trials :
| Clinical outcome | Hypothesized effect on risk | Estrogen and progestogen (CEsTooltip conjugated estrogens 0.625 mg/day p.o. + MPATooltip medroxyprogesterone acetate 2.5 mg/day p.o.) (n = 16,608, with uterus, 5.2–5.6 years follow up) | Estrogen and progestogen (CEsTooltip conjugated estrogens 0.625 mg/day p.o. + MPATooltip medroxyprogesterone acetate 2.5 mg/day p.o.) (n = 16,608, with uterus, 5.2–5.6 years follow up) | Estrogen and progestogen (CEsTooltip conjugated estrogens 0.625 mg/day p.o. + MPATooltip medroxyprogesterone acetate 2.5 mg/day p.o.) (n = 16,608, with uterus, 5.2–5.6 years follow up) | Estrogen alone (CEsTooltip Conjugated estrogens 0.625 mg/day p.o.) (n = 10,739, no uterus, 6.8–7.1 years follow up) | Estrogen alone (CEsTooltip Conjugated estrogens 0.625 mg/day p.o.) (n = 10,739, no uterus, 6.8–7.1 years follow up) | Estrogen alone (CEsTooltip Conjugated estrogens 0.625 mg/day p.o.) (n = 10,739, no uterus, 6.8–7.1 years follow up) |
| Clinical outcome | Hypothesized effect on risk | HRTooltip Hazard ratio | 95% CITooltip Confidence interval | ARTooltip Attributable risk | HRTooltip Hazard ratio | 95% CITooltip Confidence interval | ARTooltip Attributable risk |
| Coronary heart disease | Decreased | 1.24 | 1.00–1.54 | +6 / 10,000 PYs | 0.95 | 0.79–1.15 | −3 / 10,000 PYs |
| Stroke | Decreased | 1.31 | 1.02–1.68 | +8 / 10,000 PYs | 1.37 | 1.09–1.73 | +12 / 10,000 PYs |
| Pulmonary embolism | Increased | 2.13 | 1.45–3.11 | +10 / 10,000 PYs | 1.37 | 0.90–2.07 | +4 / 10,000 PYs |
| Venous thromboembolism | Increased | 2.06 | 1.57–2.70 | +18 / 10,000 PYs | 1.32 | 0.99–1.75 | +8 / 10,000 PYs |
| Breast cancer | Increased | 1.24 | 1.02–1.50 | +8 / 10,000 PYs | 0.80 | 0.62–1.04 | −6 / 10,000 PYs |
| Colorectal cancer | Decreased | 0.56 | 0.38–0.81 | −7 / 10,000 PYs | 1.08 | 0.75–1.55 | +1 / 10,000 PYs |
| Endometrial cancer | – | 0.81 | 0.48–1.36 | −1 / 10,000 PYs | – | – | – |
| Hip fractures | Decreased | 0.67 | 0.47–0.96 | −5 / 10,000 PYs | 0.65 | 0.45–0.94 | −7 / 10,000 PYs |
| Total fractures | Decreased | 0.76 | 0.69–0.83 | −47 / 10,000 PYs | 0.71 | 0.64–0.80 | −53 / 10,000 PYs |
| Total mortality | Decreased | 0.98 | 0.82–1.18 | −1 / 10,000 PYs | 1.04 | 0.91–1.12 | +3 / 10,000 PYs |
| Global index | – | 1.15 | 1.03–1.28 | +19 / 10,000 PYs | 1.01 | 1.09–1.12 | +2 / 10,000 PYs |
| Diabetes | – | 0.79 | 0.67–0.93 | | 0.88 | 0.77–1.01 | |
| Gallbladder disease | Increased | 1.59 | 1.28–1.97 | | 1.67 | 1.35–2.06 | |
| Stress incontinence | – | 1.87 | 1.61–2.18 | | 2.15 | 1.77–2.82 | |
| Urge incontinence | – | 1.15 | 0.99–1.34 | | 1.32 | 1.10–1.58 | |
| Peripheral artery disease | – | 0.89 | 0.63–1.25 | | 1.32 | 0.99–1.77 | |
| Probable dementia | Decreased | 2.05 | 1.21–3.48 | | 1.49 | 0.83–2.66 | |
| Abbreviations: CEs = conjugated estrogens. MPA = medroxyprogesterone acetate. p.o. = per oral. HR = hazard ratio. AR = attributable risk. PYs = person–years. CI = confidence interval. Notes: Sample sizes (n) include placebo recipients, which were about half of patients. "Global index" is defined for each woman as the time to earliest diagnosis for coronary heart disease, stroke, pulmonary embolism, breast cancer, colorectal cancer, endometrial cancer (estrogen plus progestogen group only), hip fractures, and death from other causes. Sources: See template. ||||||||
vte Risk of venous thromboembolism (VTE) with hormone therapy and birth control (QResearch/CPRD) :
| Type | Route | Medications | Odds ratio (95% CITooltip confidence interval) |
| Menopausal hormone therapy | Oral | Estradiol alone ≤1 mg/day >1 mg/day | 1.27 (1.16–1.39)* 1.22 (1.09–1.37)* 1.35 (1.18–1.55)* |
| Menopausal hormone therapy | Oral | Conjugated estrogens alone ≤0.625 mg/day >0.625 mg/day | 1.49 (1.39–1.60)* 1.40 (1.28–1.53)* 1.71 (1.51–1.93)* |
| Menopausal hormone therapy | Oral | Estradiol/medroxyprogesterone acetate | 1.44 (1.09–1.89)* |
| Menopausal hormone therapy | Oral | Estradiol/dydrogesterone ≤1 mg/day E2 >1 mg/day E2 | 1.18 (0.98–1.42) 1.12 (0.90–1.40) 1.34 (0.94–1.90) |
| Menopausal hormone therapy | Oral | Estradiol/norethisterone ≤1 mg/day E2 >1 mg/day E2 | 1.68 (1.57–1.80)* 1.38 (1.23–1.56)* 1.84 (1.69–2.00)* |
| Menopausal hormone therapy | Oral | Estradiol/norgestrel or estradiol/drospirenone | 1.42 (1.00–2.03) |
| Menopausal hormone therapy | Oral | Conjugated estrogens/medroxyprogesterone acetate | 2.10 (1.92–2.31)* |
| Menopausal hormone therapy | Oral | Conjugated estrogens/norgestrel ≤0.625 mg/day CEEs >0.625 mg/day CEEs | 1.73 (1.57–1.91)* 1.53 (1.36–1.72)* 2.38 (1.99–2.85)* |
| Menopausal hormone therapy | Oral | Tibolone alone | 1.02 (0.90–1.15) |
| Menopausal hormone therapy | Oral | Raloxifene alone | 1.49 (1.24–1.79)* |
| Menopausal hormone therapy | Transdermal | Estradiol alone ≤50 μg/day >50 μg/day | 0.96 (0.88–1.04) 0.94 (0.85–1.03) 1.05 (0.88–1.24) |
| Menopausal hormone therapy | Transdermal | Estradiol/progestogen | 0.88 (0.73–1.01) |
| Menopausal hormone therapy | Vaginal | Estradiol alone | 0.84 (0.73–0.97) |
| Menopausal hormone therapy | Vaginal | Conjugated estrogens alone | 1.04 (0.76–1.43) |
| Combined birth control | Oral | Ethinylestradiol/norethisterone | 2.56 (2.15–3.06)* |
| Combined birth control | Oral | Ethinylestradiol/levonorgestrel | 2.38 (2.18–2.59)* |
| Combined birth control | Oral | Ethinylestradiol/norgestimate | 2.53 (2.17–2.96)* |
| Combined birth control | Oral | Ethinylestradiol/desogestrel | 4.28 (3.66–5.01)* |
| Combined birth control | Oral | Ethinylestradiol/gestodene | 3.64 (3.00–4.43)* |
| Combined birth control | Oral | Ethinylestradiol/drospirenone | 4.12 (3.43–4.96)* |
| Combined birth control | Oral | Ethinylestradiol/cyproterone acetate | 4.27 (3.57–5.11)* |
| Notes: (1) Nested case–control studies (2015, 2019) based on data from the QResearch and Clinical Practice Research Datalink (CPRD) databases. (2) Bioidentical progesterone was not included, but is known to be associated with no additional risk relative to estrogen alone. Footnotes: * = Statistically significant (p < 0.01). Sources: See template. ||||