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medroxyprogesterone + Premarin (Premella / Premelle Ciclico / Premique Cycle)

✓ Approved

Pfizer, Inc. · ESR1 · Small Molecule

What is medroxyprogesterone + Premarin?

medroxyprogesterone + Premarin is a small molecule developed by Pfizer, Inc.. It is approved for therapeutic indications via oral (po).

Drug Profile

Brand NamesPremella, Premelle Ciclico, Premique Cycle
CompanyPfizer, Inc.
Drug ClassSmall Molecule
Molecular TargetESR1, PGR
RouteOral (PO)
StatusApproved
Sources: ClinicalTrials.gov, Pfizer, Inc.

Mechanism of Action

Molecular Targets

medroxyprogesterone + Premarin acts on 2 molecular targets:

ESR1estrogen receptor 1 (ER, ESR)
PGRprogesterone receptor (NR3C3, PR)
Want deeper analysis?Noah AI can explain complex mechanisms and compare to similar drugs.

Therapeutic Indications

medroxyprogesterone + Premarin is developed for 2 unique indications across 2 therapeutic areas.

Therapeutic AreaConditionPhase
Surgical and medical proceduresHormone replacement therapy✓ Approved
Musculoskeletal and connective tissue disordersOsteoporosis✓ Approved

Related Research Articles

PubMedAIDS care2026-09-18

Recall and understanding of HIV-related counseling messages among progestin implant and injectable contraception users in Malawi.

Chapola John Chawezi JC, Bula Agatha A, Chinula Lameck L, Tang Jennifer Hui-Yu JH

Some studies have suggested an increased risk of HIV acquisition or transmission with hormonal contraception and potential drug-antiretroviral therapy (ART) interactions. We conducted a randomized clinical trial among Malawian women with and without HIV who were initiating the levonorgestrel (LNG) implant or depot medroxyprogesterone acetate (DMPA) injectable. Women living with HIV were included to examine contraceptive use in the context of potential contraceptive-ART interactions and the effect of hormonal contraception on HIV genital shedding, and women without HIV were included because of concerns about the potential relationship between hormonal contraception and HIV acquisition. A qualitative sub-study assessed participants' recall and understanding of standardized contraceptive counseling messages.Participants for the qualitative sub-study were purposively sampled from the parent trial based on HIV status, counseling exposure, and contraceptive continuation status, and enrolled after randomization and exposure to counseling messages. Women participated in individual in-depth interviews (IDIs) and/or focus group discussions (FGDs) conducted after trial follow-up visits; interview timing varied across participants.Of 60 eligible women from the parent trial, 41 participated in IDIs and/or FGDs. Most recalled counseling messages emphasizing condom use for HIV and STI prevention among serodiscordant couples. However, none accurately recalled messages about the potential HIV acquisition risk associated with DMPA or the implant, and even when these messages were re-read, they were not accurately interpreted. In contrast, women more frequently recalled messages about potential reduced contraceptive effectiveness of the implant when used with ART. Women who continued their assigned contraceptive method were more likely to accurately recall counseling messages.Improved counseling strategies are needed to support clear communication and understanding of complex and evolving contraceptive and HIV-related risk information.

PMID 42757784
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PubMedBritish journal of cancer2026-09-17

Menopausal hormone therapy and primary liver cancer: long-term follow-up of the women's health initiative randomized trials.

Pichardo Margaret S MS, Aragaki Aaron K AK, Manson JoAnn E JE, Pan Kathy K et al.

Long-term results on liver cancer incidence and mortality are reported from two Women's Health Initiative randomized trials evaluating menopausal hormone therapy. 16,608 postmenopausal women with a uterus were randomized to conjugated equine estrogen (CEE) 0.625 mg/d plus medroxyprogesterone acetate (MPA) 2.5 mg/d or placebo and 10,739 women with hysterectomy were randomized to 0.625 mg/d of CEE-alone or placebo. After nearly 24 years follow-up and 74 incident liver cancers, neither CEE-alone nor CEE plus MPA influenced liver cancer development (CEE-alone vs placebo (11 vs 15 cancers; hazard ratio [HR] 0.75; 95% CI, 0.34-1.63; CEE plus MPA vs placebo (30 vs 18 cancers; HR 1.63; 95% CI, 0.91-2.92). CEE plus MPA did not significantly influence liver cancer mortality: 27 vs 22 deaths (HR 1.18; 95% CI, 0.67-2.07). In subgroup analyses, CEE plus MPA vs placebo was associated with more liver cancers among women aged 50-59 years (10 vs 0 cancers (P-trend 0.01) and prior oral contraceptive users (HR 4.30, 95% CI, 1.46-12.72; P-interaction 0.01). These findings indicate no overall influence of menopausal hormone therapy on liver cancer incidence or mortality although a possible increased risk with CEE plus MPA in select subgroups warrants further investigation. clinicaltrials.gov Identifier: NCT00000611.

PMID 42749856
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PubMedJournal of clinical densitometry : the official journal of the International Society for Clinical Densitometry2026-09-15

Cortical and trabecular bone changes associated with tibolone in postmenopausal women: A randomized, open-label study compared with estrogen therapy and placebo.

Cruz-Priego Griselda-Adriana GA, Guagnelli Miguel Ángel MÁ, Santiago Sergio Ortiz SO, Castrejón-Delgado Lizett L et al.

Postmenopausal bone loss affects both cortical and trabecular compartments, with oxidative stress implicated in its pathogenesis. Tibolone is a tissue-selective hormone therapy with potential skeletal and antioxidative effects, but its structural impact compared to estrogen is understudied. This study evaluated the effects of tibolone on cortical and trabecular bone parameters in postmenopausal women, compared with estrogen therapy and placebo, using three-dimensional dual-energy X-ray absorptiometry (3D-DXA). This 12-month, randomized, open-label trial included postmenopausal women aged 45-59 years, assigned to one of three groups: tibolone (2.5 mg/day), conjugated estrogens (0.625 mg/day) plus medroxyprogesterone acetate, or placebo. Bone parameters were measured at baseline, 6, and 12 months using 3D-SHAPER software. Oxidative stress markers were assessed concurrently. Longitudinal changes were analyzed using mixed-design (two-way repeated-measures) ANOVA. Of 92 randomized participants, 71 completed the study (tibolone n=22, estrogen n=27, placebo n=22). Changes in areal BMD did not exceed the least significant change of DXA measurements. Numerical increases in trabecular volumetric BMD and cortical thickness were observed in the tibolone group over 12 months, whereas numerical declines were noted in the placebo group and variable changes in the estrogen group; however, no statistically significant between-group differences were detected. Lipid peroxidation decreased in the tibolone and estrogen groups, while other oxidative stress markers remained largely unchanged. Adverse events were mild, with no statistically significant differences across groups. In this exploratory randomized study, no statistically significant between-group differences in cortical or trabecular bone parameters were detected over 12 months, and the observed changes in areal BMD did not exceed the least significant change of conventional DXA measurements. Therefore, the present study cannot establish clinically meaningful skeletal changes with tibolone. The numerical patterns observed with 3D-DXA should be considered hypothesis-generating and require confirmation in larger, adequately powered, and longer-term studies.

PMID 42743657
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PubMedClinical pharmacology : advances and applications2026-09-14

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

Mousavi Taraneh T, Hossain Md Fitrat MF, Shaya Fadia T FT, Hill Wanda W et al.

The cardiovascular, kidney, and metabolic effects of hormone replacement therapy (HRT) in postmenopausal women, particularly those who initiate treatment after age 65, remain incompletely characterized. The objective of this systematic review was to evaluate evidence on these outcomes, with a focus on women aged 65 years and older. PubMed, Embase, Scopus, and the Cochrane Library were searched for studies published between January 1, 2021, and February 28, 2026. Eligible studies included randomized controlled trials and secondary or post-trial analyses evaluating HRT in postmenopausal women, particularly women aged 65 years and older. Outcomes included cardiovascular, renal, and metabolic endpoints. Risk of bias was assessed using RoB 2 where applicable, and evidence was synthesized narratively. The review protocol was registered in PROSPERO (CRD420261338310). Of 1701 records identified, 6 reports met the inclusion criteria, all derived from three parent trials: the Women's Health Initiative Hormone Therapy Trials (WHI-HT), Early versus Late Intervention Trial with Estradiol (ELITE), and Kronos Early Estrogen Prevention Study (KEEPS). HRT effects varied by regimen and timing. In WHI-HT analyses, conjugated equine estrogens (CEE), alone or with medroxyprogesterone acetate (MPA), lowered low-density lipoprotein cholesterol (LDL-C) but increased triglycerides and systolic blood pressure; CEE plus MPA had a less favorable coronary profile than CEE alone. ELITE supported less favorable vascular effects with later initiation, while KEEPS showed neutral long-term findings. No trial was designed specifically for women aged ≥65 years, and evidence in this age group was limited to subgroup analyses of broader postmenopausal women. Additionally, no studies included renal outcomes. Future prospective studies should evaluate cardiovascular, kidney, and metabolic outcomes across HRT regimens and timing in older postmenopausal women to guide individualized treatment decisions.

PMID 42733833
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PubMedCardiology in review2026-09-04

Menopausal Hormone Therapy and Cardiovascular Risk: Current Evidence and Treatment Recommendations.

Pillai Ashwin A AA, Mehta Aryan A, Godin Shea-Lee SL, Frishman William H WH et al.

In 2025, the US Food and Drug Administration (FDA) removed its prior class-wide boxed warnings for menopausal hormone therapy (MHT), paving the way for increased clinical use. Menopause accelerates cardiovascular risk independently of chronological aging, manifesting as a 7.5% increase in carotid-femoral pulse wave velocity within 1 year and a hypertension prevalence of 66.6% in women aged 55-64 years. Risk stratification for MHT hinges on the timing of initiation and the administered formulation. The 2025 Women's Health Initiative secondary analysis suggests that in symptomatic women aged 50-59 years, combination (estrogen-progestogen) MHT maintains atherosclerotic neutrality while reducing vasomotor symptoms by 59%. Conversely, atherosclerotic risk increases in women aged 70-79 years (hazard ratio 3.22 for combined therapy). Route of administration dictates the metabolic effect: oral estrogens undergo hepatic first-pass metabolism, elevating venous thromboembolism risk and increasing triglycerides by 5-15%, whereas transdermal formulations bypass hepatic first-pass metabolism, decrease triglycerides by 5-30%, and carry a neutral thromboembolic risk profile. When concurrent progestogen therapy is required, natural micronized progesterone is favored over synthetic medroxyprogesterone acetate to preserve estrogen-mediated vascular benefits. Oral or transdermal systemic MHT can be considered for vasomotor symptom management in women <60 years or within 10 years of menopause with a 10-year atherosclerotic cardiovascular disease risk of <5% and a coronary artery calcium score of zero.

PMID 42693520
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PubMedStudies in family planning2026-09-04

Development of a Client Experience of Care Metric to Measure Person-Centered Care for Injectable Contraceptive Clients in Lilongwe, Malawi.

Felker-Kantor Erica E, Demise Eden E, Mkandawire Philip P, Rothschild Claire C et al.

The aim of this study was to develop and psychometrically assess a client-experience-of-care metric tailored for women in Lilongwe, Malawi, using self-administered or provider-administered depot medroxyprogesterone acetate subcutaneous (DMPA-SC) and to assess differences in experiences of care between the two groups. A client exit interview was administered to 400 Malawian women who had self-injected (n = 198) or received provider-administered (n = 202) DMPA-SC within the three months preceding the study. Iterative exploratory factor analysis with a polychoric matrix was performed. Cronbach's alpha was used to assess scale reliability. Bivariate and multivariate generalized linear regression models with robust standard errors were used to test for differences in client experience between self-administered and provider-administered clients. Exploratory factor analysis yielded a two-factor solution, identifying a unifying scale for client experience of care (eight items) and a subscale for empowerment (ten items). The client experience of care scale had moderate construct validity, explaining 40 percent of the variance, high criterion validity with a positive and statistically significant (p < 0.05) correlation coefficient, and low-to-moderate reliability (alpha = 0.68). In adjusted models, statistically significant differences in client experience of care were detected by injection method, with self-injecting clients reporting better experiences of care compared to provider-administered clients.

PMID 42695937
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