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Conjugated equine estrogens + medroxyprogesterone acetate

Conjugated equine estrogens + medroxyprogesterone acetate has been studied in 10 papers since 2019: 5 trials in people, 4 reviews; 6 in the past year. It has not reached trials in people. The newest story, Oct 30, 2026: “Hormone trials found no clear liver cancer effect in women”.

InterventionPreclinical

10 papers study it18 more mention it21 findingsUpdated

PubChemPubChemChEBI

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“CEE plus MPA vs placebo (30 vs 18 cancers; HR 1.63; 95% CI, 0.91-2.92)”
Menopausal hormone therapy and primary liver cancer: long-term follow-up of the women's health initiative randomized trialsBritish journal of cancer2026doi:10.1038/s41416-026-03621-9

3 of its findings point the other way.

C, W, M, H: cells, worms or flies, mice, humans. Dark: independent labs found the same change there. Light: one lab or one study. Outline: nothing yet.

Labs are independent when their papers share no last author and no institution.

Against: findings that point the other way from most findings on the same outcome.

Company ties: findings with an author at a company, or from a paper whose competing-interests statement declares ties to one.

  • 7 independent labs in 3 countries
  • 3 findings against
  • Funders: National Institutes of Health and 6 more
  • 6 of 21 findings with company ties
  • Human trial5

Studies in people

4 studies gave conjugated equine estrogens + medroxyprogesterone acetate to people and measured what changed.

What did studies of Conjugated equine estrogens + medroxyprogesterone acetate find?

11

Studies of Conjugated equine estrogens + medroxyprogesterone acetate measured 11 outcomes; the most studied are mortality (1 study), liver cancer (1) and favorable coronary profile (1).

Mortality

no changein humans1HR 1.18

1 study

  1. Conjugated equine estrogens + medroxyprogesterone acetate showed no clear effect on mortality in humans (HR, 1.18; 95% CI, 0.67–2.07).

    “After a median cumulative follow-up for liver cancer mortality of 23.7 years in the CEE-alone trial and 24.7 years in the CEE plus MPA trial, no significant effects on liver cancer specific mortality were observed.”

    Human trialn = 16,608

    Hormone trials found no clear liver cancer effect in women

    British journal of cancer

  2. Conjugated equine estrogens + medroxyprogesterone acetate showed no clear effect on mortality in humans (HR 1.18; 95% CI, 0.67-2.07).

    “CEE plus MPA did not significantly influence liver cancer mortality: 27 vs 22 deaths (HR 1.18; 95% CI, 0.67-2.07)”

    Human trial0.625 mg/d + 2.5 mg/dnearly 24 yearsfemalesn = 16,608

    Hormone trials found no clear liver cancer effect in women

    British journal of cancer

Liver cancer

no changein humans1HR 1.63

1 study

  1. Conjugated equine estrogens + medroxyprogesterone acetate showed no clear effect on liver cancer in humans (HR 1.63; 95% CI, 0.91–2.92).

    “Over cumulative follow-up, liver cancer incidence did not differ significantly between the CEE plus MPA and placebo group”

    Human trialn = 16,608

    Hormone trials found no clear liver cancer effect in women

    British journal of cancer

  2. Conjugated equine estrogens + medroxyprogesterone acetate showed no clear effect on liver cancer in humans (HR 1.63; 95% CI, 0.91-2.92).

    “CEE plus MPA vs placebo (30 vs 18 cancers; HR 1.63; 95% CI, 0.91-2.92)”

    Human trial0.625 mg/d + 2.5 mg/dnearly 24 yearsfemalesn = 16,608

    Hormone trials found no clear liver cancer effect in women

    British journal of cancer

More on Liver cancer

Favorable coronary profile

downin humans1

1 study

  1. Conjugated equine estrogens + medroxyprogesterone acetate decreases favorable coronary profile in humans (compared with CEE alone, WHI-HT analyses).

    “CEE plus MPA had a less favorable coronary profile than CEE alone”

    Reviewcompared with CEE alone, WHI-HT analysesfemales

    Cardiovascular and Metabolic Outcomes of Hormone Replacement Therapy in Women Aged 65 Years and Older: A Systematic Review of Randomized Clinical Trials

    Clinical pharmacology : advances and applications

Coronary artery disease

no changein humans1HR 0.59

1 study

  1. Conjugated equine estrogens + medroxyprogesterone acetate showed no clear effect on coronary artery disease in humans (normal low-density lipoprotein (LDL) cholesterol levels (less than 130 mg/dL)) (HR 0.59; 95% CI, 0.31-1.10).

    “the CHD risk in untreated participants with normal low-density lipoprotein (LDL) cholesterol levels (less than 130 mg/dL) was similar to that of placebo-treated participants (hazard ratio [HR] 0.59; 95% CI, 0.31-1.10)”

    Human trialnormal low-density lipoprotein (LDL) cholesterol levels (less than 130 mg/dL)oral0.625 mg/d CEE + 2.5 mg/d MPAfemales

    Influence of Cardiometabolic Status on Cardiovascular Effects of Oral Menopausal Hormone Therapy

    Obstetrics and gynecology

More on Coronary artery disease

Bone mineral density

downin humans1

1 study

  1. Conjugated equine estrogens + medroxyprogesterone acetate protects against bone mineral density in humans (osteoporosis management).

    “While on HRT, her bone density was well preserved and stable in the osteopenic range both at the lumbar spine and femoral neck.”

    Human trialosteoporosis management0.45 mg/1.5mgat least 20 yearsfemales

    SAT-783 83y Old Woman On Long-Term Hormone Replacement Therapy (HRT) for Osteoporosis (OP) Management: n of 1, Revisiting the Role of HRT in OP Management

    ENDO 2025 abstract

More on Bone mineral density

IL-6

no changein humans1

1 study

  1. Conjugated equine estrogens + medroxyprogesterone acetate showed no clear effect on IL-6 in humans.

    “No statistically significant changes were found in homocysteine or IL-6 levels.”

    Human trialoral

    The effects of oral medroxyprogesterone acetate combined with conjugated equine estrogens on inflammation in postmenopausal women: a systematic review and meta-analysis of randomized controlled trials

    Frontiers in endocrinology

More on IL-6

Homocysteine

no changein humans1

1 study

  1. Conjugated equine estrogens + medroxyprogesterone acetate showed no clear effect on homocysteine in humans.

    “No statistically significant changes were found in homocysteine or IL-6 levels.”

    Human trialoral

    The effects of oral medroxyprogesterone acetate combined with conjugated equine estrogens on inflammation in postmenopausal women: a systematic review and meta-analysis of randomized controlled trials

    Frontiers in endocrinology

More on Homocysteine

Fibrinogen

downin humans1

1 study

  1. Conjugated equine estrogens + medroxyprogesterone acetate decreases fibrinogen in humans (WMD -60.588 mg/dL (95% CI -71.436 to -49.741)).

    “a significant reduction in fibrinogen levels was observed (WMD = -60.588 mg/dL; 95% CI: -71.436 to -49.741; P < 0.001)”

    Human trialoral

    The effects of oral medroxyprogesterone acetate combined with conjugated equine estrogens on inflammation in postmenopausal women: a systematic review and meta-analysis of randomized controlled trials

    Frontiers in endocrinology

More on Fibrinogen

C-reactive protein

downin humans1

1 study

  1. Conjugated equine estrogens + medroxyprogesterone acetate decreases C-reactive protein in humans (WMD -0.173 mg/dL (95% CI -0.25 to -0.10)).

    “MPA/CEE treatment was associated with a significant decrease in CRP levels (WMD = -0.173 mg/dL; 95% CI: -0.25 to -0.10; P < 0.001)”

    Human trialoral

    The effects of oral medroxyprogesterone acetate combined with conjugated equine estrogens on inflammation in postmenopausal women: a systematic review and meta-analysis of randomized controlled trials

    Frontiers in endocrinology

More on C-reactive protein

Vulnerability

upin humans1

1 study

  1. Conjugated equine estrogens + medroxyprogesterone acetate increases vulnerability in humans (p < 0.05).

    “and increased vulnerability, a facet of neuroticism (p < 0.05).”

    Human trial0.625 mg/day conjugated equine estrogen with or without 2.5 mg/day medroxyprogesterone acetate3 monthsfemalesn = 22

    Effect of hormone therapy on personality traits: preliminary evidence in older men and women

    Climacteric : the journal of the International Menopause Society

Conscientiousness

downin humans1

1 study

  1. Conjugated equine estrogens + medroxyprogesterone acetate decreases conscientiousness in humans (p < 0.01).

    “HT in women decreased conscientiousness (p < 0.01)”

    Human trial0.625 mg/day conjugated equine estrogen with or without 2.5 mg/day medroxyprogesterone acetate3 monthsfemalesn = 22

    Effect of hormone therapy on personality traits: preliminary evidence in older men and women

    Climacteric : the journal of the International Menopause Society

What is Conjugated equine estrogens + medroxyprogesterone acetate linked with?

6

Studies link Conjugated equine estrogens + medroxyprogesterone acetate with 6 measures, most often liver cancer (1 study), bone fracture (1) and venous thromboembolism (1).

Liver cancer

upin humans1HR 2.11–4.3

1 study

  1. Conjugated equine estrogens + medroxyprogesterone acetate raises the risk of liver cancer in humans (post-intervention phase) (HR, 2.11; 95% CI, 1.06–4.18).

    “HRs for CEE plus MPA vs placebo elevated in the post-intervention phase (HR, 2.11; 95% CI, 1.06–4.18”

    Human trialpost-intervention phasen = 16,608

    Hormone trials found no clear liver cancer effect in women

    British journal of cancer

  2. Conjugated equine estrogens + medroxyprogesterone acetate raises the risk of liver cancer in humans (prior oral contraceptive users) (HR 4.30, 95% CI, 1.46-12.72).

    “prior oral contraceptive users (HR 4.30, 95% CI, 1.46-12.72; P-interaction 0.01)”

    Human trialprior oral contraceptive users0.625 mg/d + 2.5 mg/dnearly 24 yearsfemales

    Hormone trials found no clear liver cancer effect in women

    British journal of cancer

More on Liver cancer

Bone fracture

downin humans1RR 0.78

1 study

  1. Conjugated equine estrogens + medroxyprogesterone acetate lowers the risk of bone fracture in humans (postmenopausal women with an intact uterus) (RR 0.78, 95% CI 0.71 to 0.86).

    “and probably reduces the risk of all clinical fractures (RR 0.78, 95% CI 0.71 to 0.86; moderate-certainty evidence).”

    Reviewpostmenopausal women with an intact uteruscombined continuous5.6 yearsfemalesn = 16,608

    Long-term hormone therapy for perimenopausal and postmenopausal women

    The Cochrane database of systematic reviews

More on Bone fracture

Venous thromboembolism

upin humans1RR 2.03

1 study

  1. Conjugated equine estrogens + medroxyprogesterone acetate raises the risk of venous thromboembolism in humans (postmenopausal women with an intact uterus) (RR 2.03, 95% CI 1.55 to 6.64).

    “and venous thromboembolism (RR 2.03, 95% CI 1.55 to 6.64; low-certainty evidence).”

    Reviewpostmenopausal women with an intact uteruscombined continuous5.6 yearsfemalesn = 16,608

    Long-term hormone therapy for perimenopausal and postmenopausal women

    The Cochrane database of systematic reviews

More on Venous thromboembolism

Stroke

upin humans1RR 1.39

1 study

  1. Conjugated equine estrogens + medroxyprogesterone acetate raises the risk of stroke in humans (postmenopausal women with an intact uterus) (RR 1.39, 95% CI 1.09 to 2.09).

    “It may increase the risk of stroke (RR 1.39, 95% CI 1.09 to 2.09; low-certainty evidence)”

    Reviewpostmenopausal women with an intact uteruscombined continuous5.6 yearsfemalesn = 16,608

    Long-term hormone therapy for perimenopausal and postmenopausal women

    The Cochrane database of systematic reviews

More on Stroke

Coronary artery disease

upin humans1HR 2.77

1 study

  1. Conjugated equine estrogens + medroxyprogesterone acetate raises the risk of coronary artery disease in humans (elevated LDL 190 mg/dL or higher in untreated postmenopausal women) (HR 2.77; 95% CI, 1.42-5.40).

    “for elevated LDL 190 mg/dL or higher, the risks were more than doubled (HR 2.77; 95% CI, 1.42-5.40; P -trend=.002).”

    Human trialelevated LDL 190 mg/dL or higher in untreated postmenopausal womenoral0.625 mg/d CEE + 2.5 mg/d MPAfemales

    Influence of Cardiometabolic Status on Cardiovascular Effects of Oral Menopausal Hormone Therapy

    Obstetrics and gynecology

More on Coronary artery disease

Breast cancer

upin humans1RR 1.27

1 study

  1. Conjugated equine estrogens + medroxyprogesterone acetate raises the risk of breast cancer in humans (intact uterus) (RR 1.27, 95% CI 1.03 to 1.56).

    “combined continuous hormone therapy probably increases the risk of breast cancer (RR 1.27, 95% CI 1.03 to 1.56; moderate-certainty evidence)”

    Reviewintact uterusoral5.6 yearsfemalesn = 16,608

    Long-term hormone therapy for perimenopausal and postmenopausal women

    The Cochrane database of systematic reviews

More on Breast cancer

Latest

Dec 2025: 0Jan 2026: 0Feb 2026: 0Mar 2026: 0Apr 2026: 0May 2026: 0Jun 2026: 2Jul 2026: 1Aug 2026: 1Sep 2026: 3Oct 2026: 0Nov 2026: 07 papers in 12 months
British Journal of Cancer

Hormone trials found no clear liver cancer effect in women

Liver cancers numbered 11 versus 15 with estrogen alone and 30 versus 18 with combined hormones, each compared with placebo.Liver cancers numbered 11 versus 15 with estrogen alone and 30 versus 18 with combined hormones, each compared with placebo.

Randomized trialLiver cancer
Paper

See all 28

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