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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

PubMedCJC open2026-09-18

Decommissioning of Durable Left Ventricular Assist Devices.

El-Andari Ryaan R, Buchholz Holger H, Conway Jennifer J, Pidborochynski Tara T et al.

Cardiac recovery following durable left ventricular assist device (LVAD) implantation is the ideal outcome for heart failure patients. Traditionally, the durable LVAD has required explantation. We describe our single-centre experience with LVAD decommissioning. LVAD decommissioning involved making a sternotomy or sub-xiphoid incision, ligating the outflow graft, and removing the driveline by transecting the driveline inside and outside of the chest. Six patients underwent durable LVAD decommissioning from 2017-2024. One patient had a HeartWare (Medtronic, Galway, Ireland) device, 3 patients had a HeartMate II (Abbott, Abbott Park, IL), and 2 patients had a HeartMate 3 (Abbott). All patients were successfully decommissioned and discharged without mechanical circulatory support.

PMID 42756474
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PubMedIBRO neuroscience reports2026-09-18

Modulation of spatial learning and memory by cannabinoid-estrogen interaction in an AD-like cognitive impairment: The role of cannabinoid receptors and BDNF protein.

Mirshekar Mohammad Ali MA, Nadi Farzaneh F, Fanaei Hamed H, Chahkandi Mohadeseh M

Alzheimer's disease (AD) is an increasingly prevalent neurodegenerative disorder worldwide, with women showing a higher risk of developing the disease. The decline in steroid hormones after menopause may contribute to the increased susceptibility of women to neurodegenerative conditions. In parallel, cannabis-derived compounds have been reported to alleviate certain symptoms associated with neurological disorders. The present study was designed to investigate the effects of marijuana extract on cognitive impairment and hippocampal molecular markers in an ovariectomized AD-like rat model, and to evaluate whether co-administration with estradiol modifies these effects. The marijuana extract used in this study was characterized by HPLC and was found to contain 8.5% Δ9-THC. AD-like cognitive impairment pathology was induced by intra-hippocampal administration of Aβ25-35 in OVX rats. Animals were treated with marijuana extract (60 mg/kg/day, corresponding to approximately 5.1 mg/kg/day Δ9-THC) either alone or in combination with 17β-estradiol (1 mg/kg every 4 days) for 28 days. Cognitive performance was evaluated using the Morris water maze (MWM). In addition, hippocampal CB1/CB2 receptor expression and BDNF protein levels were measured to examine potential molecular associations. Our findings showed that chronic administration of the marijuana extract improved Aβ25-35-induced deficits in spatial learning and memory. Alterations in CB1 receptor expression and BDNF levels accompanied these behavioral effects. Notably, co-treatment with estradiol did not produce a synergistic effect, suggesting a complex interaction between cannabinoid-related and estrogen-related signaling pathways. These preclinical findings suggest that a THC-standardized marijuana extract may exert neuroprotective-like effects in an AD-like cognitive impairment model. However, because the extract was not fully phytochemically characterized and the mechanistic analyses were correlational, the results should be interpreted cautiously. Further studies are needed to clarify the underlying mechanisms and translational relevance of these findings.

PMID 42756662
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PubMedFrontiers in psychology2026-09-18

Gonadal hormones and impulsivity facets: moderating roles of cortisol and anxiety.

Barel Efrat E, Cohen Ami A, Mahagna Lila L

Impulsivity is a multidimensional construct that reflects both affective reactivity and cognitive control processes. Although gonadal hormones have been implicated in impulsive behavior, their associations with specific impulsivity facets may depend on contextual physiological and affective conditions. In this study, we ask whether internal neuroendocrine and psychological states moderate associations between gonadal hormones and impulsivity facets. Salivary levels of testosterone, estradiol, and cortisol are assessed in a mixed sample of 197 participants comprised of 66 men, 68 users of oral contraceptives, and 63 naturally cycling women in the mid-luteal phase. Participants complete the four facets of the Urgency-Premeditation-Perseverance-Sensation (UPPS) Impulsive Behavior scale and a measure of state anxiety. Moderated regression analyses examine whether cortisol levels and anxiety moderate associations between gonadal hormones and impulsivity facets. Results indicate that hormonal associations with impulsivity are context-dependent. Cortisol and anxiety moderate associations between gonadal hormones and regulatory facets of impulsivity. In particular, estradiol shows context-dependent associations with lack of premeditation and lack of perseverance, whereas testosterone is associated with perseverance at higher anxiety levels. These effects are specific to regulatory facets of impulsivity and are not observed for urgency or sensation-seeking. The findings suggest that associations between gonadal hormones and impulsive behavior may be contingent upon concurrent neuroendocrine and psychological contexts.

PMID 42755796
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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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PubMedTranslational animal science2026-09-18

Effect of single implant and re-implant strategies on growth performance and carcass characteristics in finishing cattle.

Smith Zachary K F ZKF, Francis Becca G BG, Word Alyssa B AB, Waite Audie A et al.

Three randomized complete block design experiments evaluated a single implant strategy versus approved re-implant strategies in feedlot cattle using trenbolone acetate (TBA) and estradiol-based implants. Revalor implants were from Merck Animal Health; Synovex implants were from Zoetis. Exp. 1: A total of 1400 steers (initial BW = 320 kg), housed in open lot, dirt-surfaced pens with a concrete apron, were assigned to either a single Revalor-XS (initial 80 mg TBA + 16 mg E2; delayed 120 mg TBA + 24 mg E2) administered 209 d pre-harvest (XS) or a re-implant strategy of Synovex-Choice (100 mg TBA + 14 mg EB) on d 0 followed by Synovex-ONE Feedlot (200 mg TBA + 28 mg EB) 60 d later (CHSOF). Pen served as the experimental unit. Initial BW differed and was included as a covariate. CHSOF increased (P = 0.01) DMI, and numerically increased ADG and HCW relative to XS, XS numerically improved net energy utilization by 2.27% (P ≤ 0.12). Exp. 2: Steers (n = 480; initial BW = 388 kg) were assigned to 48 open lot, dirt-surfaced pens with a concrete apron (10 steers/pen). A 2 × 3 factorial compared XS vs. CHSOF (re-implant at 70 d) across harvest times of 162, 183, or 204 DOF. Pen served as the experimental unit. Implant strategy had minimal effect on performance and carcass traits; increasing DOF increased (P ≤ 0.01) HCW, rib fat, and ribeye area. Exp. 3: Beef × Dairy heifers, (n = 685) and steers (n = 660; initial BW ≈ 167-170 kg) received CHSOF (d 100 and 200), CHPLUS (Choice d 200, Synovex Plus d 300), or Revalor strategies: XS (steers) or XH (heifers; lower estradiol dose) at d 100 (RevX100) or d 200 (RevX200). Cattle were hosued in open lot, dirt-surfaced pens with a concrete apron. Individual animal served as the experimental unit. RevX100 and RevX200 produced heavier (P ≤ 0.01) HCW than CHPLUS, while CHPLUS improved (P ≤ 0.01) yield grade. In conclusion, a single extended-release implant (Revalor-XS/XH) performs comparably to Synovex re-implant programs in cattle finished over 200 to 400 DOF.

PMID 42757368
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PubMedBiochemical and biophysical research communications2026-09-18

Complementary roles of Smad6 and Smad7 in BMP-15-mediated steroidogenic regulation in granulosa cells.

Soejima Yoshiaki Y, Yamamoto Koichiro K, Iwata Nahoko N, Motohashi Kanon K et al.

Bone morphogenetic proteins (BMPs), members of the transforming growth factor (TGF)-β superfamily, play essential roles in ovarian follicular development and steroidogenesis. Although inhibitory Smads (Smad6 and Smad7) negatively regulate BMP/TGF-β signaling, their roles in ovarian steroidogenesis remain unclear. Here, we investigated the effects of Smad6 and Smad7 on BMP-15-mediated steroidogenic regulation using human granulosa-like KGN cells and primary rat granulosa cells. Of note, siRNA-mediated knockdown of Smad6 enhanced BMP-15-induced Smad1/5/9 phosphorylation and Id-1 expression, whereas Smad7 knockdown increased basal Id-1 expression independently of BMP-15 in KGN cells. BMP-15 reduced progesterogenic StAR expression and this effect was enhanced by Smad6 or Smad7 knockdown. In addition, BMP-15 increased metabolization of progesterone by 20αHSD induction under Smad7-knockdown conditions, whereas aromatase expression was unaffected by BMP-15 regardless of Smad6 or Smad7 knockdown. In primary rat granulosa cells, combined knockdown of Smad6 and Smad7 significantly reduced basal and FSH-induced progesterone production without affecting estradiol production. Collectively, these results suggest that inhibitory Smad6 and Smad7 differentially and complementarily regulate BMP-15 signaling and progesterone synthesis in granulosa cells, contributing to the fine-tuning of ovarian BMP signaling and luteinization.

PMID 42759274
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