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.^[3]

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[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	135843-32-2
PubChem CID	75124299
Chemical and physical data
3D model (JSmol)	Interactive image
SMILES 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 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

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

• v
• t
• e

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 alone (CEsTooltip Conjugated estrogens 0.625 mg/day p.o.) (n = 10,739, no uterus, 6.8–7.1 years follow up)
		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.

• v
• t
• e

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)*
		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.

Society and culture

Due to a lawsuit against pharma company Wyeth, it was revealed that Wyeth had contracted with a medical ghostwriting company to produce favorable medical literature about Prempro for marketing purposes. The ghostwriting company arranged for academics to put their names on research papers that had been prepared by the company in consultation with Wyeth. This process produced "more than 50 peer reviewed journal articles for HRT", among other material. The academics were not paid, but these ghostwritten papers helped easily pad their CVs.^[5]

See also

• Estradiol/medroxyprogesterone acetate
• Estradiol cypionate/medroxyprogesterone acetate
• List of combined sex-hormonal preparations