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Preclinical pharmacological profile of nomegestrol acetate, a synthetic 19-nor-progesterone derivative.

BACKGROUND: Nomegestrol acetate (NOMAC), a synthetic progestogen derived from 19-nor-progesterone, recently completed clinical trials for use with 17beta-estradiol in a new monophasic combined oral contraceptive. In this review, published as well as previously unpublished preclinical studies that detail the effects of NOMAC on estrogenic, progestogenic, and androgenic systems, as well as mineralocorticoid, glucocorticoid, bone, and metabolic indices are described. METHODS: In vitro assays to determine NOMAC structure-activity relationships used tissue derived from rat uteri. Transactivation p…

Association of Hormonal Contraceptive Use With Adverse Health Outcomes: An Umbrella Review of Meta-analyses of Randomized Clinical Trials and Cohort Studies.

IMPORTANCE: Meta-analyses have reported conflicting data on the safety of hormonal contraception, but the quality of evidence for the associ … ms included hormonal contraception, contraceptive agents, progesterone, desogestrel, norethindrone, megestrol, algestone, norprogesterones, and levonorgestrel combined with terms such as systematic review or meta-analysis. EVIDENCE REVIEW: The methodological quality of each meta-analysis was graded using the Assessment of Multiple Systematic Reviews, versi …

Assessment of risk factors for mortality in patients with cardiovascular disease and a history of treatment for malignancy.

BACKGROUND: Patients with advanced cancer after radio- and/or chemotherapy are increasingly commonly hospitalised in cardiology units due to … tent somatic symptoms who were treated with tamoxifen, angiotensin-converting enzyme inhibitors and megestrol acetate. CONCLUSIONS: This is the first study that evaluated the combined effect of oncological and cardiovascular risk factors on survival of patients with CVD and coexisting cancer after radio- and/or chemotherapy treatment. When the three groups …

Comparison of three different treatment modalities in the management of cancer cachexia.

AIMS AND BACKGROUND: The optimal treatment of cancer cachexia remains unknown. In this study, we compared the efficacy of three different treatment modalities in the management of cancer cachexia. METHODS: Sixty-two assessable cachectic cancer patients were randomized to one of the following three arms: 1) megesterol acetate (MA) plus meloxicam (n = 23); 2) MA plus meloxicam plus oral eicosapentaenoic acid (EPA)-enriched nutritional supplement (n = 21); or 3) meloxicam plus oral EPA-enriched nutritional supplement (n = 18). Treatment duration was 3 months. RESULTS: The treatment arms were we

Occult myometrial recurrence after progesterone therapy to preserve fertility in a young patient with endometrial cancer.

OBJECTIVE: We report a case of endometrial cancer treated by fertility-preserving P therapy, who subsequently presented with an abnormal magnetic resonance imaging (MRI) of the myometrium despite normal endometrial biopsies. DESIGN: Case report. SETTING: Tertiary referral university hospital. PATIENT(S): A 31-year-old patient with grade 1, stage I endometrial cancer presented for treatment with fertility-preserving P therapy. Multiple endometrial samples were all normal. Four years later, she presented with an abnormal pelvic MRI in the absence of any other signs or symptoms. Hysterectomy a

Progestin-only pills for contraception.

BACKGROUND: The introduction of a new progestin-only oral contraceptive in Europe has renewed interest in this class of oral contraceptives. … 30 μg had higher efficacy than did the pill containing norethisterone 350 μg. An early trial found megestrol acetate inferior to other progestin-only pills in terms of efficacy. A study of the timing of pill initiation after birth found no important differences, but high losses to follow up undermined the trial. AUTHORS' CONCLUSIONS: Evidence is insuffici …

Ongoing or previous mental disorders predispose to adverse mood reporting during combined oral contraceptive use.

PURPOSE: Previous studies have emphasised that women with pre-existing mood disorders are more inclined to discontinue hormonal contraceptive use. However, few studies have examined the effects of combined oral contraceptives (COC) on mood in women with previous or ongoing mental disorders. MATERIALS AND METHODS: This is a supplementary analysis of an investigator-initiated, double-blinded, randomised clinical trial during which 202 women were treated with either a COC (1.5 mg estradiol and 2.5 mg nomegestrolacetate) or placebo during three treatment cycles. The Mini International Neuropsychi…

The sexuological impact of hormonal contraceptives based on their route of administration.

Evidence on the effects of hormonal contraceptives on female sexuality is conflicting. We enrolled 556 women, divided into six groups: two composed of subjects using a combined hormonal contraceptive (COC) containing 0.020 ("COC20") and 0.030 ("COC30") mg of ethynyl estradiol (EE), "natural", using COC containing 1.5 mg of estradiol (E2), "ring", using a vaginal ring releasing each day 0.015 mg of EE + 0.120 of etonogestrel, "subcutaneous", using a progestin only subcutaneous contraceptive implant releasing etonogestrel and "controls", using no hormonal contraceptive methods. The subjects were

Mismatch repair status influences response to fertility-sparing treatment of endometrial cancer.

BACKGROUND: Patients younger than 40 years usually present with early-stage endometrial cancer with favorable prognosis. However, such patients are usually in their childbearing age and may desire fertility-sparing options. The identification of biomarkers may improve the clinical outcomes in these patients and aid in fertility-sparing management; however, there has been no reports on biomarker analysis so far. OBJECTIVE: This study aimed to evaluate the prognostic significance of Proactive Molecular Risk Classifier for Endometrial Cancer in the fertility-sparing management of endometrial can

Pregnancy outcomes after fertility-sparing management in young women with early endometrial cancer.

OBJECTIVE: To analyze pregnancy outcomes in young women with stage IA, grade 1 endometrioid adenocarcinoma of the uterus after successful fertility-sparing management using progestin. METHODS: We reviewed the medical records of 141 women with stage IA, grade 1 endometrioid adenocarcinoma of the uterus who had complete remission after progestin treatment. Statistical analysis was performed using Student's t test or Mann-Whitney U test for continuous variables, using χ or Fisher's exact test for categorical variables, and using log-rank test for survival comparison. RESULTS: Fifty-four (38.3%)

[Tumour anorexia--tumour cachexia in case of gastrointestinal tumours: standards and visions].

The development of progressive malnutrition or cachexia is frequent in patients with gastrointestinal cancer - especially in patients with a carcinoma of the pancreas. The cachexia syndrome which is characterised by loss of body weight, negative nitrogen balance and fatigue significantly affects patients' quality of life, morbidity and survival. Because the currently established therapeutical strategies are often disappointing many physicians tended to develop a therapeutical nihilism. Cancer anorexia and cachexia are two distinct syndromes which may have synergistic effects in a patient. This

The estrogenic activity of synthetic progestins used in oral contraceptives enhances fatty acid synthase-dependent breast cancer cell proliferation and survival.

Overexpression of the lipogenic enzyme fatty acid synthase (FAS) is a common molecular feature in subsets of sex-steroid-related tumors incl … slightly stimulated after exposure to two other progestins, medroxy-progesterone acetate (MPA) and megestrol acetate (MGA), which are used in postmenopausal hormone replacement therapy and high-dose progestin treatment therapy. Western blot analyses showed that NOR-induced stimulation of FAS activity correlated closely with NOR-induced up-regulation of FAS …

Cancer cachexia: mechanisms and clinical implications.

Cachexia is a multifactorial process of skeletal muscle and adipose tissue atrophy resulting in progressive weight loss. It is associated with poor quality of life, poor physical function, and poor prognosis in cancer patients. It involves multiple pathways: procachectic and proinflammatory signals from tumour cells, systemic inflammation in the host, and widespread metabolic changes (increased resting energy expenditure and alterations in metabolism of protein, fat, and carbohydrate). Whether it is primarily driven by the tumour or as a result of the host response to the tumour has yet to be

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… In a 3-month intervention period, patients were randomized to either EPA-enriched ONS plus placebo liquid suspension, standard ONS plus megestrol acetate suspension, or EPA-enriched ONS plus megestrol acetate suspension. … Weight gain was highest in the megestrol acetate group but unfortunately body composition was not assessed and so changes in water weight cannot be controlled for. …

Non-conventional dosing of oral anticancer agents in oncology and malignant haematology: a systematic review protocol.

BackgroundRecent advances in cancer therapeutics have resulted in significantly improved overall survival and progression-free survival for patients. Targeted oral systemic anticancer therapies (SACT) offer a range of treatment approaches that differ from traditional cytotoxic chemotherapy: non-cytotoxic oral SACT target malignant disease continuously, have less broad and more favourable safety profiles, which can improve patients' quality of life (QoL). Toxicities associated with daily oral SACT administration can, however, result in non-adherence and a reduced QoL. Non-conventional dosing of

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… Megestrol/ or Megestrol Acetate/ 69. norethisterone.mp. or Norethindrone/ 70. Diethylstilbestrol/ 71. Ethinyl Estradiol/ or ethinylestradiol.mp. 72. Idarubicin/ 73. Methotrexate/ 74. Trifluridine/ 75. lenvatinib.mp. 76. venetoclax.mp. 77. ixazomib.mp. 78. … Megestrol/or Megestrol Acetate/ 69. norethisterone.mp. or Norethindrone/ 70. Diethylstilbestrol/ 71. Ethinyl Estradiol/or ethinylestradiol.mp. 72. Idarubicin/ 73. Methotrexate/ 74. Trifluridine/ 75. lenvatinib.mp. 76. venetoclax.mp. 77. ixazomib.mp. 78. …

Therapeutic strategies against cancer cachexia.

Cancer cachexia has two main components: anorexia and metabolic alterations. The main changes associated with the development of this multi-organic syndrome are glucose intolerance, fat depletion and muscle protein hypercatabolism. The aim of this paper is to review the more recent therapeutic approaches designed to counteract the wasting suffered by the cancer patient with cachexia. Among the most promising approaches we can include the use of ghrelin agonists, beta-blockers, beta-adrenergic agonists, androgen receptor agonists and anti-myostatin peptides. The multi-targeted approach seems es

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… Interestingly, in experimental animals, megestrol acetate increases not only food intake but also lean mass and physical performance. 23 Nanocrystal suspensions of megestrol acetate are easy to use and represent an improvement in bioavailability. 24 Megestrol acetate is the standard drug in cancer cachexia … A new look at an old drug for the treatment of cancer cachexia: megestrol acetate. Clin Nutr 2013;32:319-24. 23. Busquets S, Serpe R, Sirisi S, et al. Megestrol acetate: its impact on muscle protein metabolism supports its use in cancer cachexia. Clin Nutr 2010;29:733-7. 24. …

Continued medical treatment for persistent early endometrial cancer in young women.

OBJECTIVE: We aimed to investigate the effectiveness of continuing medical therapy in patients who did not achieve complete response (CR) despite 9 months of progestin treatment. We also sought to determine the prognostic factors associated with achieving CR among these patients. METHODS: We retrospectively analyzed 51 patients with presumed stage IA, grade 1 or 2 endometrioid adenocarcinoma who had persistent disease on biopsy performed at 9-12 months after at least 9 months of progestin-based therapy. Data on clinicopathological factors and oncological and obstetrical outcomes following con

Aromatase inhibitors for treatment of advanced breast cancer in postmenopausal women.

BACKGROUND: Hormonal treatments for advanced or metastatic breast cancer, such as tamoxifen and the progestins megestrol acetate and medroxyprogesterone acetate, have been in use for many years. Aromatase inhibitors (AIs) are a class of compounds that systemically inhibit oestrogen synthesis in the peripheral tissues. Aminoglutethimide was the first AI in clinical use (first generation) and had a similar tumour-regressing effect to other endocrine treatments, which showed the potential of this alternative type of therapy. Other AIs have since been developed and the third generation AIs anastro…

Cancer cachexia--pathophysiology and management.

About half of all cancer patients show a syndrome of cachexia, characterized by anorexia and loss of adipose tissue and skeletal muscle mass. Cachexia can have a profound impact on quality of life, symptom burden, and a patient's sense of dignity. It is a very serious complication, as weight loss during cancer treatment is associated with more chemotherapy-related side effects, fewer completed cycles of chemotherapy, and decreased survival rates. Numerous cytokines have been postulated to play a role in the etiology of cancer cachexia. Cytokines can elicit effects that mimic leptin signaling a

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… Progestins Megestrol acetate (MA) and medroxyprogesterone acetate (MPA) are synthetic, orally active progestational agents. … Tchekmedyian NSN Hickman MM Siau JJ Greco FAF Keller JJ Browder HH Megestrol acetate in cancer anorexia and weight loss Cancer 1992 69 5 1268 1274 10.1002/cncr.2820690532 1739926 121. …