Estradiol valerate 2mg / Cyproterone 1mg tablets

BackgroundNo conceptually new drugs for the safe and successful cure of endometriosis are likely to become available soon. Hormonal modulation of ovarian function and suppression of menstruation remain the pillars of disease control. However, existing drugs may be used following novel modalities to limit the consequences of endometriosis progression.ObjectivesThe aims of this review were to propose a pharmacological approach aimed at limiting the potential detrimental effects of the recent dramatic increase in postmenarcheal repetitive ovulatory menses and to define the type of hormones and the routes of administration that can be used to maximize safety and tolerability in the medical treatment of endometriosis.MethodsFor this narrative review, we selected the best quality evidence, prioritizing RCTs, systematic reviews, meta-analyses, network meta-analyses, and international guidelines, preferably published in the last decade.OutcomeMedical treatment of endometriosis should be included into all aspects of prevention. Very-low-dose combined oral contraceptives can be used for years to counteract the increased risk of ovarian cancer observed in patients with endometriosis. This primary prevention measure saves lives and can effectively integrate targeted risk-reducing surgery. Secondary pharmacological prevention, based on a working diagnosis of early onset adenomyosis-endometriosis selectively in adolescents with severe dysmenorrhea and heavy menstrual bleeding, can potentially impede the development of advanced disease forms, and reduce the need for management of complications due to a delay in diagnosis and treatment. Tertiary prevention, i.e., medical therapy of established disease, is based initially on the safest available estrogen-progestogen combinations and progestogen monotherapies. Whenever possible, ethinyl estradiol and cyproterone acetate should be avoided because of thromboembolic and meningioma risks, respectively. Estradiol can be administered transdermally. Switching to gonadotropin-releasing hormone agonists and antagonists should not be delayed when the first-line agents fail.Conclusions and outlookTwo-thirds of symptomatic endometriosis patients can be managed satisfactorily for many years using, with the right modality, the existing safe, effective, and well-tolerated medications. Despite the constant plea for new drugs, this already appears to be an excellent clinical outcome, unsurpassed when managing other human chronic inflammatory diseases. Cohort studies are needed to verify whether turning off the recurrent inflammation caused by repeated ovulation and menstruation could also affect the risk of systemic conditions associated with endometriosis.

Abstract licence: CC BY

ObjectiveTo evaluate (1) the metabolic and endocrine effects of metformin combined with exenatide versus only metformin treatments in patients with polycystic ovary syndrome (PCOS) and abdominal obesity (AO) and (2) to determine the molecular mechanisms by which the combined treatment acts on PCOS patients.DesignRandomized controlled trial of PCOS patients with AO to receive combined treatment with metformin-exenatide or metformin alone, and network pharmacology of gene expression in PCOS patients under the combined exposure.SettingTertiary teaching hospital.PatientsWomen with PCOS and AO who fulfilled the Rotterdam Criteria under combined treatment with daily cyclical ethinylestradiol (35 μg/day) and cyproterone acetate (2 mg/day).InterventionPatients were randomized to either combined oral metformin (1500 mg/day) and exenatide (2 mg weekly subcutaneous injection, n = 35 women) treatment or metformin alone (n = 31 women) for 12 weeks. Network pharmacological prediction of gene expression under the combined exposure was studied.Main outcome measures(1) Basal and after both treatments anthropometric, endocrine, and metabolic changes were compared. (2) Network pharmacological prediction and gene expression were studied in patients under metformin-exenatide treatment. Venn diagram and Markov Cluster Algorithm diagram of core targets for AO were applied to identify key targets.ResultsBoth treatments displayed (1) reductions of total testosterone, insulin, and lipoprotein levels and (2) increases of high-density lipoprotein cholesterol and apolipoprotein A1. We identified PCOS, AO, and comorbid genes further intersected with 269 combination therapy genes. Network pharmacology identified 154 key PCOS genes for drug regulation, including 29 closely related to AO and metabolism.ConclusionBoth treatments improved glucose and lipid metabolism, weakening insulin resistance and improving some biochemical indexes. Network pharmacology identified genes related to AO and metabolism in patients with PCOS under the metformin-exenatide treatment.Trial registrationClinicalTrials.gov NCT04029272.

Abstract licence: CC BY-NC

Endometriosis is associated with nociceptive pain, as well as peripheral and central sensitization. Evidence-based treatment suggestions for controlling endometriosis should be based on the convergence of the best scientific evidence, physicians' clinical expertise, and the values and priorities of individual patients. In this non-systematic, comprehensive narrative review, data from available randomized controlled trials and meta-analyses on hormonal treatment for symptomatic endometriosis are interpreted through the lens of clinical experience. The role of patients in defining therapeutic trade-off balances is also taken into consideration. Most symptomatic patients benefit from hormonal therapy, including first-line (progestogens and estrogen-progestogen combinations) and second-line (GnRH agonists and antagonists) medications, to relieve nociceptive pain. To reduce the risk of venous and arterial thrombosis and avoid stimulating lesions, it is preferable to use combinations containing body-identical estrogens rather than ethinyl-estradiol. The main adverse effect of first-line medications is irregular bleeding, which adversely impacts efficacy, tolerability, and adherence. If progestogens and estrogen-progestogens do not improve health-related quality of life (HRQoL), promptly stepping up to GnRH analogues combined with add-back therapy is indicated. Add-on rather than upfront combination therapy is suggested. Separating the analogues and add-back therapy allows for choosing the compounds that best suit the characteristics of individual patients. Transdermal body-identical estradiol use is proposed in combination with both progestogens and GnRH analogues. Similar satisfactory outcomes are achieved with GnRH agonists and antagonists. Evidence on the use of neuromodulatory drugs to treat neuropathic and nociplastic pain is derived from studies of other chronic pain conditions and shows limited effectiveness. The two mainstays of hormonal therapy are (i) ovariostasis and (ii) amenorrhea. "Medical treatment failure" should not be declared unless a shift from first-line to second-line medications has been undertaken whenever these conditions are not met. For severely symptomatic adolescents and young women, secondary prevention through ovariostasis and amenorrhea should be pursued promptly to improve HRQoL, halt lesion progression, and preserve reproductive potential.

Abstract licence: CC BY