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estradiol +levonorgestrel (Fem7 Plus / HRT, Merck)

✓ Approved

Merck KGaA · ESR1 · Small Molecule

What is estradiol +levonorgestrel?

estradiol +levonorgestrel is a small molecule developed by Merck KGaA. It is approved for therapeutic indications via topical or transdermal.

Drug Profile

Brand NamesFem7 Plus, HRT, Merck
CompanyMerck KGaA
Drug ClassSmall Molecule
Molecular TargetESR1, PGR
RouteTopical, Transdermal
StatusApproved
Sources: ClinicalTrials.gov, Merck KGaA

Mechanism of Action

Molecular Targets

estradiol +levonorgestrel 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

estradiol +levonorgestrel is developed for 1 unique indication across 1 therapeutic area.

Therapeutic AreaConditionPhase
Surgical and medical proceduresHormone replacement therapy✓ Approved

Related Research Articles

PubMedDomestic animal endocrinology2026-07-25

Association of intra-follicular melatonin with reduced oxidative DNA damage and improved oocyte quality in water buffalo: Effect of season and follicular size.

Pandey Anand Kumar AK, Gunwant Pankaj P, Kumar Sandeep S, Saini Gitesh G et al.

Oxidative stress caused by production of reactive oxygen species (ROS) due to normal metabolism and/or external environment results in changes in follicular fluid microenvironment, oxidation of oocyte DNA (8‑hydroxy-2'deoxyguanosine levels; 8-OHdG) and poor-quality oocyte. Therefore, the present investigation was designed to evaluate the relationship between oocyte quality and intra-follicular environment (melatonin, 8-OHdG, 17β-estradiol and progesterone concentrations) in different sized follicles during summer and winter in water buffaloes. Slaughterhouse-derived ovaries were subjected for collection of follicular fluid from three (n = 42 each category in summer and winter) different categories of follicle based on diameter (Small: 8-9.9 mm; Medium: 10-11.9 mm; Large: 12-14 mm). Individual follicles were treated as independent observational units and analyzed using a factorial model including effects of season, follicular size, and their interaction. The results revealed higher (P < 0.05) melatonin and 17β-estradiol concentrations were associated with larger follicles and improved oocyte quality. Melatonin was positively associated (P < 0.05) with 17β-estradiol concentrations in different follicular categories during both seasons. Conversely, 8-OHdG followed an inverse association (P < 0.05) with melatonin in different categories of follicles during both seasons. Irrespective of follicles size, data revealed that good-quality oocytes (Grade A) were associated with higher melatonin concentrations, 102.11±3.88 pg/mL and 116.59±3.32 pg/mL in summer and winter, respectively. Ordinal logistic regression analysis identified melatonin concentration as the only significant independent predictor of oocyte quality (β=-0.226, OR=0.798; P < 0.001). Thus, it may be concluded that higher intra-follicular melatonin concentrations were associated with lower oxidative DNA damage and improved oocyte quality in water buffalo.

PMID 42497647
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PubMedWorld journal of otorhinolaryngology - head and neck surgery2026-07-25

Sex Hormones and the Risk of Nasal Polyps: A Two-Sample Mendelian Randomization Study.

Zhu Ying Y, Zhou Jia-Yao JY, Zhang Shi-Yao SY, Tang Ru R et al.

The pathophysiological roles of sex hormones in airway inflammation have drawn much attention recently. We aimed to explore the causal effect of sex hormones on chronic rhinosinusitis (CRS) and nasal polyps (NP) via a Mendelian randomization (MR) study. Genetic traits for serum bioavailable testosterone (BioT), total testosterone (ToT), sex hormone-binding globulin (SHBG), and estradiol were extracted from a genome-wide association study (GWAS) containing 425,097 European individuals from the UK Biobank, while outcome data were obtained from the FinnGen data set. Two-sample MR analysis was performed to assess the association of sex hormones and NP or CRS with the inverse variance weighted method as the main analysis, together with sensitivity analyses. Genetically predicted BioT levels showed a possible inverse association with both NP (OR = 0.669, p = 0.009) and CRS (OR = 0.792, p = 0.014) in the overall population, though these associations were marginally above the traditional significance threshold after multiple testing correction (FDR = 0.054). Sex-stratified analyses revealed potentially stronger protective associations in females, with higher BioT associated with lower odds of NP. No significant causal effects of estradiol or SHBG on NP or CRS were identified in the available GWAS data. Our MR analyses suggest a possible inverse relationship between genetically predicted serum BioT levels and the risk of both CRS and NP, with potentially stronger effects in females. Further observational and experimental studies are necessary to validate these genetic associations and explore the potential immunomodulatory mechanisms by which testosterone may influence sinonasal inflammation.

PMID 42500089
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PubMedAmerican journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons2026-07-25

Contraception Use Differs Across Solid Organ Transplant Types Among Women Transplanted in Reproductive Age.

Cooper Katherine M KM, Mahle Rachael E RE, Joyal Kayla K, Le Mariesa M et al.

There are a growing number of reproductive age solid organ transplant (SOT) recipients, yet comparative data on contraception use across organ types are limited. We performed a retrospective cohort study of women who underwent first-time liver, kidney, heart, or lung transplantation between the ages of 18 and 45 from 2015 and 2025 using TriNetX (n=10,155). Contraception uptake within two years was assessed by organ, including patterns of initial contraceptive choice and subsequent changes in contraception choice, and clinical outcomes, including osteoporosis, thromboembolism, and graft rejection, were compared by contraception type. Among 10,155 eligible SOTR, 19.9% had documented contraception within two years of SOT (heart 27.3%, lung 22.5%, kidney 19.7%, liver 16.8%, p<0.001). Combined oral contraception was the most common initial contraception method, followed by depot medroxyprogesterone acetate (DMPA). However, those who started on DMPA were more likely to switch medications. Compared with no contraception, DMPA was associated with increased osteoporosis, hypertension, thrombosis, and graft rejection, whereas estradiol-containing agents were not. Overall, contraception use after SOT was extremely uncommon with exceedingly low rates of highly effective options, particularly after liver and kidney transplant. Higher switching and adverse associations with DMPA support early, organ-tailored contraceptive counseling and careful method selection post-SOT.

PMID 42498172
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PubMedClinical nutrition ESPEN2026-07-25

Betaine supplementation has no effect on sex hormones in premenopausal women with overweight or obesity: A randomized controlled trial.

Zawieja Emilia E, Młodzik-Czyżewska Monika M, Chmurzyńska Agata A

Betaine supplementation has been shown to increase total testosterone concentrations in physically active men. However, its effects in women have not yet been investigated. The aim of the study was to evaluate the effect of eight weeks of betaine supplementation on sex hormone concentrations in women with overweight and obesity. This was a double-blind, randomized controlled trial. Premenopausal women (18-45 years; n = 36) with overweight or obesity received either 3 g/day of betaine (BET) or a placebo (PLA) for eight weeks. Each participant attended two study meetings (before and after the supplementation) at the Department of Human Nutrition and Dietetics, Poznań University of Life Sciences, Poland between September 2024 and April 2025. Biological samples were collected before and after supplementation to assess sex hormone concentrations, which were measured using ELISA. There were no significant time × treatment interactions in the concentrations of sex hormones: plasma testosterone concentration: p = 0.496, salivary testosterone concentration: p = 0.882, plasma DHEA-S concentration: p = 0.498, plasma SHBG concentration: p = 0.775, plasma estradiol concentration: p = 0.378, plasma cortisol: p = 0.504. No statistically significant effect of betaine supplementation was detected on sex hormone concentrations in premenopausal women with overweight or obesity, however larger and longer-term studies are warranted to confirm these findings. Clinical trial registry entry: https://clinicaltrials.gov/study/NCT06344377.

PMID 42498161
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PubMedEnvironmental toxicology2026-07-25

Effect of Propylparaben on In Vitro Maturation of Porcine Oocytes and Embryo Development.

Núñez-Macías Elivier E, Casillas Fahiel F, Ramírez-Jara Yenny Y, Casas Eduardo E et al.

Parabens are synthetic chemicals that, due to their antibacterial and fungicidal effects, are widely used as preservatives in food, cosmetics, and personal care products, such as shampoos, hair conditioners, body creams, soaps, deodorants, makeup, wet wipes, lotions, female hygiene products, and vaginal lubricants. Several years ago, they were considered noncytotoxic, but studies have since shown that parabens act as endocrine disruptors due to their similarity to estradiol and could interfere with fertility. In recent decades, they have been associated with decreased fertility in the population. Although there are studies showing the effect of various parabens on reproduction, there are few related to the effect of propylparaben (PrPB) on oocyte maturation and embryo development. The present study aimed to evaluate the in vitro effect of PrPB on oocyte maturation and embryo development. The calculated lethal concentration (LC50) and concentration of inhibition of maturation (IM50) for both events was 140 μM. After 144 h post fertilization, the viability of developed embryos was reduced according to the PrPB increased. The total number of dividing embryos was classified from two blastomeres to late blastocyst. In all concentrations, there was embryo development, except in the concentration 300 μM, in which all were dead. The results of this study provide evidence that PrPB could affect female reproductive health by reducing oocyte maturation and delaying early embryo development. Therefore, further studies are required to explore the possible mechanisms producing the damage caused by the constant use of products containing PrPB.

PMID 42498988
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PubMedJournal of assisted reproduction and genetics2026-07-25

Association of daily perceived stress with fertility outcomes in natural and controlled ovarian stimulation cycles: a feasibility study.

Strohl Harmonie H, Do Nguyen N, Ryu Howon H, Dayo Olumayowa O et al.

Females with infertility perceive stress, but most studies rely on single assessments. We examined the feasibility of repeated ecological momentary assessment (EMA) during IVF and whether stress trajectories across two cycles were associated with reproductive and IVF outcomes. In a prospective cohort at a single academic center, 26 females (18-42 years) undergoing IVF with luteal estradiol priming were recruited; 25 completed follow-up. Perceived stress was assessed via text-message EMA three times daily during a priming month and the subsequent controlled ovarian stimulation (COS) cycle. Primary outcomes were ovulation in the priming cycle and a composite poor COS outcome (cycle cancellation, < 4 oocytes retrieved, no blastocyst, or no euploid blastocyst). Functional principal components analysis characterized stress trajectories, and regression models tested associations with outcomes. Mean age was 36 (SD 3.6); 64% were White and 24% Hispanic. All participants ovulated during priming. Two stress patterns explained 96% of follicular-phase variability. The dominant pattern (early decline then plateau) was not associated with outcomes. A second pattern (peak around cycle day 6 with subsequent rise) was associated with lower peak LH (b - 2.85, 95% CI - 4.60 to - 1.06; adjusted p = 0.004). Ten participants (40%) met the composite poor COS outcome, which was not associated with either stress pattern. Stress levels were similar between priming and COS. EMA is feasible during IVF. In patients reporting mild-to-moderate stress, perceived stress was stable and not associated with key IVF outcomes, though specific trajectories may modestly relate to hypothalamic-pituitary-ovarian-axis function.

PMID 42498851
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