Conjugated estrogens/medroxyprogesterone acetate

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Conjugated estrogens/medroxyprogesterone acetate
Combination of
Conjugated estrogensEstrogen
Medroxyprogesterone acetateProgestogen
Clinical data
Trade namesPrempro, Premphase, Premique
Other namesCEs/MPA; CEEs/MPA
AHFS/Drugs.comProfessional Drug Facts
Pregnancy
category
  • AU: D[1]
  • Contraindicated
Routes of
administration
By mouth
ATC code
  • none
Legal status
Legal status
  • UK: POM (Prescription only) [2]
  • 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.[3]

In 2018, it was the 308th most commonly prescribed medication in the United States, with more than 1 million prescriptions.[4]

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[edit]

References[edit]

  1. ^ a b "Conjugated estrogens / medroxyprogesterone Use During Pregnancy". Drugs.com. 16 February 2019. Retrieved 5 May 2020.
  2. ^ "Premique Low Dose 0.3mg/1.5mg Modified Release Tablets - Summary of Product Characteristics (SmPC)". (emc). 1 November 2016. Retrieved 5 May 2020.
  3. ^ Hochadel M, Avorn J (1 January 2007). The AARP Guide to Pills: Essential Information on More Than 1,200 Prescription and Nonprescription Medications, Including Generics. Sterling Publishing Company Incorporated. pp. 235–. ISBN 978-1-4027-4446-4.
  4. ^ "Conjugated Estrogens; Medroxyprogesterone - Drug Usage Statistics". ClinCalc. Retrieved 7 October 2022.

External links[edit]