conjugated estrogens
Regulatory sources consulted
Approved indications
- Short-term treatment of abnormal uterine bleeding due to hormonal imbalance in the absence of organic pathology.
Contraindications
Absolute
- Undiagnosed abnormal genital bleeding; known, suspected, or prior breast cancer; or estrogen-dependent neoplasia.
- Active or prior deep-vein thrombosis or pulmonary embolism; active or prior arterial thromboembolic disease; or known thrombophilia.
- Liver disease, severe hypersensitivity to components, or pregnancy.
Clinical warnings
- Boxed warning · Even with short-term use, estrogen-related risks of endometrial and breast cancer, stroke, venous thrombosis, and pulmonary embolism must be considered. — openFDA label, spl_set_id 87e2da8d-432c-4ed5-67a1-dc26294b2295; spl_id 97a59d56-720c-42fd-86b7-00ad93752452
- Major warning · Investigate persistent or recurrent bleeding and stop if thromboembolism, sudden visual loss, cholestatic jaundice, or severe hypersensitivity is suspected. — openFDA label, spl_set_id 87e2da8d-432c-4ed5-67a1-dc26294b2295; spl_id 97a59d56-720c-42fd-86b7-00ad93752452
Adverse events
Common (≥1%)
Headache · Breast pain · Nausea · Vaginal bleeding
Rare but serious
Deep-vein thrombosis or pulmonary embolism · Stroke or myocardial infarction · Anaphylaxis or angioedema
Pregnancy and lactation
Contraindicated during pregnancy. Estrogens pass into milk and may reduce its quantity or quality; the clinical team should decide how to manage breastfeeding.
Recent literature (PubMed)
The neurokinin 3 receptor antagonist fezolinetant 45 mg/d significantly reduced frequency/severity of moderate to severe vasomotor symptoms (VMS) of menopause compared with placebo in two phase 3 randomized controlled trials. Its efficacy relative to available therapies is unknown. We conducted a systematic review and Bayesian network meta-analysis to compare efficacy with fezolinetant 45 mg and hormone therapy (HT) and non-HT for VMS in postmenopausal women. Using OvidSP, we systematically searched multiple databases for phase 3 or 4 randomized controlled trials in postmenopausal women with ≥7 moderate to severe VMS per day or ≥50 VMS per week published/presented in English through June 25, 2021. Mean change in frequency and severity of moderate to severe VMS from baseline to week 12 and proportion of women with ≥75% reduction in VMS frequency at week 12 were assessed using fixed-effect models. The network meta-analysis included data from the pooled phase 3 fezolinetant trials plus 23 comparator publications across the outcomes analyzed (frequency, 19 [34 regimens]; severity, 6 [7 regimens]; ≥75% response, 9 [15 regimens]). Changes in VMS frequency did not differ significantly between fezolinetant 45 mg and any of the 27 HT regimens studied. Fezolinetant 45 mg reduced the frequency of moderate to severe VMS events per day significantly more than all non-HTs evaluated: paroxetine 7.5 mg (mean difference [95% credible interval {CrI}], 1.66 [0.63-2.71]), desvenlafaxine 50 to 200 mg (mean differences [95% CrI], 1.12 [0.10-2.13] to 2.16 [0.90-3.40]), and gabapentin ER 1800 mg (mean difference [95% CrI], 1.63 [0.48-2.81]), and significantly more than placebo (mean difference, 2.78 [95% CrI], 1.93-3.62]). Tibolone 2.5 mg (the only HT regimen evaluable for severity) significantly reduced VMS severity compared with fezolinetant 45 mg. Fezolinetant 45 mg significantly reduced VMS severity compared with desvenlafaxine 50 mg and placebo and did not differ significantly from hi
To evaluate the efficacy and safety of pharmacological treatments for vasomotor symptoms (VMS) in postmenopausal women. A systematic search was conducted in PubMed, Embase, and the Cochrane Library through January 2025. Eligible studies were Phase 3 or 4 randomized controlled trials (RCTs) assessing pharmacological treatments for moderate to severe VMS with ≥ 12 weeks of follow-up. A Bayesian random-effects network meta-analysis estimated mean differences (MDs) and risk ratios (RRs) with 95 % credible intervals (CrI). Treatments were ranked using surface under the cumulative ranking (SUCRA). Risk of bias was assessed using Cochrane's tool. Forty-one RCTs (n = 14,743; mean age 53.4 years) were included. Synthetic conjugated estrogens (SCE) 1.25 mg showed the greatest reduction in VMS frequency (MD -5.69; 95 % CrI -7.93 to -3.38), while drospirenone 0.5 mg + estradiol 0.5 mg was most effective for severity (MD -1.06; 95 % CrI -1.39 to -0.72). Most treatments had safety profiles similar to placebo, though estradiol 0.5 mg + dydrogesterone 2.5 mg was linked to more adverse events (RR 1.56; 95 % CrI 1.16 to 2.24). No significant differences in serious adverse events were found. SUCRA rankings highlighted SCE and transdermal estradiol gel as most effective for frequency, while drospirenone + estradiol led for severity. Fezolinetant and elinzanetant showed moderate efficacy. Of the studies, 22 had low risk of bias, and 19 had some concerns. Conjugated estrogens and drospirenone with estradiol are the most effective options for reducing VMS frequency and severity, and Fezolinetant and Elinzanetant showed moderate efficacy, with overall similar safety across treatments.
Targeting the interleukin-6 (IL-6)/glycoprotein 130 (GP130) signaling pathway holds significant promise for cancer therapy given its essential role in the survival and progression of various cancer types. We have identified that bazedoxifene (BZA), a Food and Drug Administration (FDA)-approved drug used for the prevention of postmenopausal osteoporosis, when combined with conjugated estrogens in Duavee, also has a novel function as an inhibitor of IL-6/GP130 interaction. BZA is currently under investigation for its potential anticancer therapeutic function through the inhibition of the IL-6/GP130 pathway. Numerous studies have highlighted the efficacy of BZA (monotherapy or combined with other chemotherapy drugs) in impeding progression across multiple cancers. In this review, we mainly focus on the anticancer activity of BZA and the underlying anticancer mechanism through inhibition of the IL-6/GP130 pathway, aiming to provide valuable insights for the design and execution of further research and the potential repositioning of BZA in oncological clinical trials.
Estrogens play an important role throughout a woman's life; therefore, disrupting their physiological production will alter hormonal balance with consequences for estrogen-related conditions, such as endometriosis and adenomyosis. The gut microbiome (GM) plays a critical role in regulating systemic estrogen concentrations, since a number of microorganisms present in the GM possess the enzyme β-glucuronidase (β-GLC), a key factor in regulating host estrogen metabolism. Although most studies have focused on the conversion of estrogen glucuronides to active estrogens by β-GLC in gut bacteria, it is known that the GM also contains steroid sulfatases (STS), which are able to convert inactive sulfated estrogens to active ones. This is especially important because estrone (E1) sulfate (E1S) is quantitatively the most important estrogen in the human and can be readily converted to E1 and estradiol (E2). It has been shown that estrogen sulfates are present in bile and can therefore reach the intestines, raising the possibility of biologically active E1 and E2 formation in the intestine by bacterial enzyme transformation. Everything depends on the presence of sulfatases in the GM, and in this respect, STS have been found in a variety of microbial species. This means that sulfatases are poised to reactivate estrogens, which are then capable of undergoing enterohepatic recirculation and exerting systemic effects throughout the body. Given that estrogen sulfates represent the largest component of circulating estrogens that are secreted by the liver into the intestines via the bile, the role of gut microbial sulfatases may be superior to that of β-GLC.
Traumatic hyphema is the entry of blood into the anterior chamber, the space between the cornea and iris, following significant injury to the eye. Hyphema may be associated with significant complications that uncommonly cause permanent vision loss. Complications include elevated intraocular pressure, corneal blood staining, anterior and posterior synechiae, and optic nerve atrophy. People with sickle cell trait or disease may be particularly susceptible to increases in intraocular pressure and optic atrophy. Rebleeding is associated with an increase in the rate and severity of complications. To assess the effectiveness of various medical interventions in the management of traumatic hyphema. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2022, Issue 3); MEDLINE Ovid; Embase.com; PubMed (1948 to March 2022); the ISRCTN registry; ClinicalTrials.gov; and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP). The last date of the search was 22 March 2022. Two review authors independently assessed the titles and abstracts of all reports identified by the electronic and manual searches. We included randomized and quasi-randomized trials that compared various medical (non-surgical) interventions versus other medical interventions or control groups for the treatment of traumatic hyphema following closed-globe trauma. We applied no restrictions on age, gender, severity of the closed-globe trauma, or level of visual acuity at time of enrollment. We used standard methodological procedures expected by Cochrane and assessed the certainty of evidence using GRADE. We included 23 randomized and seven quasi-randomized studies with a total of 2969 participants. Interventions included antifibrinolytic agents (systemic and topical aminocaproic acid, tranexamic acid, and aminomethylbenzoic acid), corticosteroids (systemic and topical), cycloplegics, miotics, aspi