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Combined estrogen–progestogen formulations
Conjugated estrogens/medroxyprogesterone acetate
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    Conjugated estrogens/medroxyprogesterone acetate

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    Conjugated estrogens/medroxyprogesterone acetate
    Combination of
    Conjugated estrogens Estrogen
    Medroxyprogesterone acetate Progestogen
    Clinical data
    Trade names Prempro, Premphase, Premique
    Other names CEs/MPA; CEEs/MPA
    AHFS/Drugs.com Professional Drug Facts
    Pregnancy
    category
    • AU: D
    • Contraindicated
    Routes of
    administration    		 By mouth
    ATC code
    • none
    Legal status
    Legal status
    • UK: POM (Prescription only)
    • US: ℞-only
    • In general: ℞ (Prescription only)
    Identifiers
    CAS Number
    PubChem CID
    Chemical and physical data
    3D model (JSmol)
    • CC1CC2C(CCC3(C2CCC3(C(=O)C)OC(=O)C)C)C4(C1=CC(=O)CC4)C.CC12CCC3C(C1CCC2=O)CCC4=C3C=CC(=C4)OS(=O)(=O)O.CC12CCC3C(=CCC4=C3C=CC(=C4)OS(=O)(=O)O)C1CCC2=O.CC12CCC3=C(C1CCC2=O)C=CC4=C3C=CC(=C4)OS(=O)(=O)O
    • InChI=1S/C24H34O4.C18H22O5S.C18H20O5S.C18H18O5S/c1-14-12-18-19(22(4)9-6-17(27)13-21(14)22)7-10-23(5)20(18)8-11-24(23,15(2)25)28-16(3)26;3*1-18-9-8-14-13-5-3-12(23-24(20,21)22)10-11(13)2-4-15(14)16(18)6-7-17(18)19/h13-14,18-20H,6-12H2,1-5H3;3,5,10,14-16H,2,4,6-9H2,1H3,(H,20,21,22);3-5,10,14,16H,2,6-9H2,1H3,(H,20,21,22);2-5,10,16H,6-9H2,1H3,(H,20,21,22)/t14-,18+,19-,20-,22+,23-,24-;14-,15-,16+,18+;14-,16+,18+;16-,18-/m0110/s1
    • Key:OZPWNCNLFBVVEN-RFYLDXRNSA-N

    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.

    Results of the Women's Health Initiative (WHI) menopausal hormone therapy randomized controlled trials
    Clinical outcome Hypothesized
    effect on risk     		Estrogen and progestogen
    (CEs 0.625 mg/day p.o. + MPA 2.5 mg/day p.o.)
    (n = 16,608, with uterus, 5.2–5.6 years follow up)     		Estrogen alone
    (CEs 0.625 mg/day p.o.)
    (n = 10,739, no uterus, 6.8–7.1 years follow up)
    HR 95% CI AR HR 95% CI AR
    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.
    Risk of venous thromboembolism (VTE) with hormone therapy and birth control (QResearch/CPRD)
    Type Route Medications Odds ratio (95% CI)
    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)*
    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)*
    Estradiol/medroxyprogesterone acetate 1.44 (1.09–1.89)*
    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)
    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)*
    Estradiol/norgestrel or estradiol/drospirenone 1.42 (1.00–2.03)
    Conjugated estrogens/medroxyprogesterone acetate 2.10 (1.92–2.31)*
    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)*
    Tibolone alone 1.02 (0.90–1.15)
    Raloxifene alone 1.49 (1.24–1.79)*
    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)
    Estradiol/progestogen 0.88 (0.73–1.01)
    Vaginal Estradiol alone 0.84 (0.73–0.97)
    Conjugated estrogens alone 1.04 (0.76–1.43)
    Combined birth control Oral Ethinylestradiol/norethisterone 2.56 (2.15–3.06)*
    Ethinylestradiol/levonorgestrel 2.38 (2.18–2.59)*
    Ethinylestradiol/norgestimate 2.53 (2.17–2.96)*
    Ethinylestradiol/desogestrel 4.28 (3.66–5.01)*
    Ethinylestradiol/gestodene 3.64 (3.00–4.43)*
    Ethinylestradiol/drospirenone 4.12 (3.43–4.96)*
    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.

    See also

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