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2.
Anticancer Res ; 40(11): 5995-6002, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33109537

RESUMO

Steroid contraceptive hormones may promote human papilloma virus (HPV) - DNA integration into the host genome, may bind to specific HPV-DNA sequences within transcriptional regulatory regions, and may modulate cell apoptosis. Most epidemiological studies, reported in this narrative review, have shown that oral contraception is associated with a 1.5-3.3-fold higher relative risk of cervical carcer, but only in users for >5 years and especially in HPV-positive women. The relative risk declines with increasing time since last use and is not different from that of never users after >10 years. Ten-year oral contraceptive use from the age of 20 years is associated with an increase in the cumulative incidence of invasive cervical cancer at the age of 50 years of approximately 1 case per 1,000. Oral contraception has a very small negative impact on the absolute risk of cancer of the uterine cervix.


Assuntos
Anticoncepcionais/efeitos adversos , Estrogênios/efeitos adversos , Progestinas/efeitos adversos , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/etiologia , Feminino , Humanos , Papillomaviridae/fisiologia , Fatores de Risco , Neoplasias do Colo do Útero/virologia
3.
Cochrane Database Syst Rev ; 9: CD012658, 2020 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-32909630

RESUMO

BACKGROUND: In the absence of treatment, endometrial hyperplasia (EH) can progress to endometrial cancer, particularly in the presence of histologic nuclear atypia. The development of EH results from exposure of the endometrium to oestrogen unopposed by progesterone. Oral progestogens have been used as treatment for EH without atypia, and in some cases of EH with atypia in women who wish to preserve fertility or who cannot tolerate surgery. EH without atypia is associated with a low risk of progression to atypia and cancer; EH with atypia is where the cells are structurally abnormal, and has a higher risk of developing cancer. Oral progestogen is not always effective at reversing the hyperplasia, can be associated with side effects, and depends on patient adherence. The levonorgestrel-intrauterine system (LNG-IUS) is an alternative method of administration of progestogen and may have some advantages over non-intrauterine progestogens. OBJECTIVES: To evaluate the effectiveness and safety of the levonorgestrel intrauterine system (LNG-IUS) in women with endometrial hyperplasia (EH) with or without atypia compared to medical treatment with non-intrauterine progestogens, placebo, surgery or no treatment. SEARCH METHODS: We searched the following databases: the Cochrane Gynaecology and Fertility Group (CGF) Specialised Register, CENTRAL, MEDLINE, Embase, CINAHL and PsycINFO, and conference proceedings of 10 relevant organisations. We handsearched references in relevant published studies. We also searched ongoing trials in ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry, and other trial registries. We performed the final search in May 2020. SELECTION CRITERIA: Randomised controlled trials (RCTs) and cross-over trials of women with a histological diagnosis of endometrial hyperplasia with or without atypia comparing LNG-IUS with non-intrauterine progestogens, placebo, surgery or no treatment. DATA COLLECTION AND ANALYSIS: Two review authors independently performed study selection, risk of bias assessment and data extraction. Our primary outcome measures were regression of EH and adverse effects associated with the LNG-IUS device (such as pelvic inflammatory disease, device expulsion, uterine perforation) when compared to treatment with non-intrauterine progestogens, placebo, surgery or no treatment. Secondary outcomes included hysterectomy, hormone-related adverse effects (such as bleeding/spotting, pelvic pain, breast tenderness, ovarian cysts, weight gain, acne), withdrawal from treatment due to adverse effects, satisfaction with treatment, and cost or resource use. We rated the overall quality of evidence using GRADE methods. MAIN RESULTS: Thirteen RCTs (1657 women aged 22 to 75 years) met the inclusion criteria. Two studies had insufficient data for meta-analysis, thus the quantitative analysis included 11 RCTs. All trials evaluated treatment duration of six months or less. The evidence ranged from very low to moderate quality: the main limitations were risk of bias (associated with lack of blinding and poor reporting of study methods), inconsistency and imprecision. LNG-IUS versus non-intrauterine progestogens Primary outcomes Regression of endometrial hyperplasia The LNG-IUS probably improves regression of EH compared with non-intrauterine progestogens at short-term follow-up (up to six months) (OR 2.94, 95% CI 2.10 to 4.13; I² = 0%; 10 RCTs, 1108 participants; moderate-quality evidence). This suggests that if regression of EH following treatment with a non-intrauterine progestogen is assumed to be 72%, regression of EH following treatment with LNG-IUS would be between 85% and 92%. Regression of EH may be improved by LNG-IUS compared with non-intrauterine progestogens at long-term follow-up (12 months) (OR 3.80, 95% CI 1.75 to 8.23; 1 RCT, 138 participants; low-quality evidence), Adverse effects associated with LNG-IUS There was insufficient evidence to determine device-related adverse effects; only one study reported on expulsion with insufficient data for analysis. Secondary outcomes The LNG-IUS may be associated with fewer hysterectomies (OR 0.26, 95% CI 0.15 to 0.46; I² = 19%; 4 RCTs, 452 participants; low-quality evidence), fewer withdrawals from treatment due to hormone-related adverse effects (OR 0.41, 95% CI 0.12 to 1.35; I² = 0%; 4 RCTs, 360 participants; low-quality evidence) and improved patient satisfaction with treatment (OR 5.28, 95% CI 2.51 to 11.10; I² = 0%; 2 RCTs, 202 participants; very low-quality evidence) compared to non-intrauterine progestogens. The LNG-IUS may be associated with more bleeding/spotting (OR 2.13, 95% CI 1.33 to 3.43; I² = 78%; 3 RCTs, 428 participants) and less nausea (OR 0.52, 95% CI 0.28 to 0.95; I² = 0%; 3 RCTs, 428 participants) compared to non-intrauterine progestogens. Data from single trials for mood swings and fatigue had a similar direction of effect as for bleeding/spotting, nausea and weight gain. There was insufficient evidence to determine cost or resource use. LNG-IUS versus no treatment Regression of endometrial hyperplasia One study demonstrated that the LNG-IUS is associated with regression of EH without atypia (OR 78.41, 95% CI 22.86 to 268.97; I² = 0%; 1 RCT, 190 participants; moderate-quality evidence) compared with no treatment. This study did not report on any other review outcome. AUTHORS' CONCLUSIONS: There is moderate-quality evidence that treatment with LNG-IUS used for three to six months is probably more effective than non-intrauterine progestogens at reversing EH in the short term (up to six months) and long term (up to two years). Adverse effects (device-related and hormone-related) were poorly and incompletely reported across studies. Very low quality to low-quality evidence suggests the LNG-IUS may reduce the risk of hysterectomy, and may be associated with more bleeding/spotting, less nausea, less withdrawal from treatment due to adverse effects, and increased satisfaction with treatment, compared to non-intrauterine progestogens. There was insufficient evidence to reach conclusions regarding device-related adverse effects, or cost or resource use.


Assuntos
Anticoncepcionais Femininos/administração & dosagem , Dispositivos Intrauterinos Medicados , Levanogestrel/administração & dosagem , Adulto , Idoso , Viés , Anticoncepcionais Femininos/efeitos adversos , Hiperplasia Endometrial/tratamento farmacológico , Hiperplasia Endometrial/patologia , Hiperplasia Endometrial/cirurgia , Feminino , Humanos , Histerectomia/estatística & dados numéricos , Expulsão de Dispositivo Intrauterino , Dispositivos Intrauterinos Medicados/efeitos adversos , Levanogestrel/efeitos adversos , Pessoa de Meia-Idade , Náusea/etiologia , Pacientes Desistentes do Tratamento/estatística & dados numéricos , Satisfação do Paciente/estatística & dados numéricos , Progestinas/administração & dosagem , Progestinas/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Indução de Remissão , Fatores de Tempo , Hemorragia Uterina/etiologia , Ganho de Peso , Adulto Jovem
4.
Artigo em Inglês | MEDLINE | ID: mdl-32732107

RESUMO

It is well established that unopposed estrogen, either endogenous or therapeutic, can induce endometrial hyperplasia and potentially endometrial cancer (EC). Anovulatory cycles, obesity, and insulin resistance are major risk factors for EC. Progestogen (progesterone and progestin), including levonorgestrel intrauterine device, are able to prevent or to treat hyperplasia, atypical hyperplasia, and even well-differentiated EC, as presented in this review. During menopausal hormone therapy, progestogens protect the endometrium against the proliferative effects of estrogens in women with a uterus. Whereas, recent epidemiologic data suggest that micronized progesterone (MP) is apparently safer for the breast, it could be less efficient than synthetic progestin on the endometrium. However, several studies from biopsies during treatment with MP do not show any increased risk of hyperplasia. Lack of compliance could explain the results on EC.


Assuntos
Hiperplasia Endometrial , Neoplasias do Endométrio , Hiperplasia Endometrial/induzido quimicamente , Neoplasias do Endométrio/epidemiologia , Endométrio , Terapia de Reposição de Estrogênios/efeitos adversos , Estrogênios , Feminino , Humanos , Progesterona/efeitos adversos , Progestinas/efeitos adversos
5.
Artigo em Inglês | MEDLINE | ID: mdl-32739288

RESUMO

Natural progesterone (P4) has a unique pharmacodynamic activity and safety profile compared to the synthetic progestins. As a result, a class effect does not exist for both P4 and synthetic progestins, in terms of both their efficacy and safety. Progestogens act at the genomic level by binding to the nuclear receptors and modulating the expression of some target-genes. P4 and the synthetic progestins have a hugely variable affinity for binding not only to the P4 receptors but also to other members of the steroid receptor family including glucocorticoid receptor, androgen receptor and mineralocorticoid receptor. This leads to different and specific pharmacokinetic profiles, clinical pharmacodynamics, safety and efficacy. P4 produced in the luteal phase of the menstrual cycle has several physiological effects regulating menses and, in the pregnant uterus, controlling the development of endometrial receptivity preparing the endometrium for implantation. P4 and its associated metabolites are powerful biological agents through genomic action by the progesterone nuclear receptor with a finely tuned regulatory role throughout pregnancy, from conception until delivery. Extra-nuclear, non-classical mechanisms of action have also been identified, including steroid interactions with some membrane receptors [oxytocin receptors and γ-aminobutyric acid (GABAA), and the induction of a direct relaxing effect on uterine contractility by blockage of calcium influx. The extent of activity of P4 on the central nervous system (CNS) is modulated by the route of administration: oral P4 is affected by the presence of bacteria and associated enzymes secreted in the gut, the intestinal wall and by the liver, whereas vaginal P4 is not. P4 and two important metabolites, namely, allopregnanolone (3a,5a-tetrahydroP4) and 3a,5a-tetrahydrodeoxycorticosterone, exert neuroprotective effects on neonates. They are also natural positive modulators of the neuronal GABAA receptor, providing a clear pathway to explain the rapid dose-dependent psychopharmacological actions including anxiolytic, antidepressant, anaesthetic, anticonvulsant and analgesic effects. Fundamental structural differences exist between P4 and the synthetic progestins, resulting in different safety profiles when they are used during the menstrual cycle, in early and late pregnancy and in the alleviation of peri- or postmenopausal symptoms.


Assuntos
Progesterona , Progestinas , Endométrio , Feminino , Humanos , Recém-Nascido , Ciclo Menstrual , Gravidez , Progestinas/efeitos adversos , Receptores de Progesterona , Útero
6.
Artigo em Inglês | MEDLINE | ID: mdl-32698992

RESUMO

This chapter explores the role of progesterone and progestogens in the management of abnormal uterine bleeding (AUB). Progestogens are used to regulate intermenstrual bleeding and decrease heavy menstrual bleeding (HMB) in women of reproductive age or who are perimenopausal. In menopausal women, progesterones and progestogens prevent endometrial hyperplasia and aim to reduce the development of endometrial cancer. We hope to make clear current best practice including preparation, specific benefits and risks. Progesterone also acts in concert with other hormones to affect breast, cardiovascular system, lipid profile and bone. We hope to explain how its unintended side effects may be used beneficially or may cause intended side effects.


Assuntos
Menorragia , Metrorragia , Feminino , Humanos , Progesterona/efeitos adversos , Progestinas/efeitos adversos , Hemorragia Uterina/induzido quimicamente
7.
MMWR Morb Mortal Wkly Rep ; 69(14): 405-410, 2020 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-32271729

RESUMO

"U.S. Medical Eligibility Criteria for Contraceptive Use" (U.S. MEC) 2016 provides evidence-based guidance for the safe use of contraceptive methods among U.S. women with certain characteristics or medical conditions (1). The U.S. MEC is adapted from global guidance from the World Health Organization (WHO) and kept up to date through continual review of published literature (1). CDC recently evaluated the evidence and the updated WHO guidance on the risk for human immunodeficiency virus (HIV) acquisition among women using hormonal contraception and intrauterine devices (IUDs) (2). After careful review, CDC adopted WHO's 2019 updated guidance for inclusion in the U.S. MEC guidance; CDC's updated guidance states that progestin-only injectable contraception (including depot medroxyprogesterone acetate [DMPA]) and IUDs (including levonorgestrel-releasing and copper-bearing) are safe for use without restriction among women at high risk for HIV infection (U.S. MEC category 1 [previously U.S. MEC category 2, advantages outweigh risks]) (Box). CDC's guidance also adds an accompanying clarification for women who wish to use IUDs, which states "Many women at a high risk for HIV infection are also at risk for other sexually transmitted diseases (STDs). For these women, refer to the recommendations in the 'U.S. Medical Eligibility Criteria for Contraceptive Use' for women with other factors related to STDs, and the 'U.S. Selected Practice Recommendations for Contraceptive Use' on STD screening before IUD insertion" (1,3). Recommendations for other hormonal contraceptive methods (including combined hormonal methods, implants, and progestin-only pills) remain the same; there is also no restriction for their use among women at high risk for HIV infection (U.S. MEC category 1). Finally, CDC clarified that the U.S. MEC recommendations for concurrent use of hormonal contraceptives or IUDs and antiretroviral use for treatment of HIV infection also apply to use of antiretrovirals for prevention of HIV acquisition (preexposure prophylaxis [PrEP]).


Assuntos
Contraceptivos Hormonais/administração & dosagem , Definição da Elegibilidade/organização & administração , Dispositivos Intrauterinos , Progestinas/administração & dosagem , Centers for Disease Control and Prevention, U.S. , Contraceptivos Hormonais/efeitos adversos , Feminino , Infecções por HIV/epidemiologia , Infecções por HIV/prevenção & controle , Humanos , Dispositivos Intrauterinos/efeitos adversos , Gravidez , Gravidez não Planejada , Progestinas/efeitos adversos , Medição de Risco , Estados Unidos/epidemiologia
8.
Trials ; 21(1): 121, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-32000820

RESUMO

BACKGROUND: Preterm birth accounts for 75% of perinatal deaths and more than 50% of long-term neurological disabilities. For a singleton pregnancy, progesterone treatment is effective in prevention of preterm birth in women with an asymptomatic short cervix or a history of preterm birth. However, a large proportion of preterm births still is not currently preventable. The aim of this study is to determine whether early universal use of oral progesterone before 14 + 0 weeks of gestation can prevent preterm birth better than universal screening of cervical length at 18 + 0 to 23 + 6 weeks of gestation, followed by progesterone treatment in those with a short cervix in singleton pregnancy. METHODS: This is a multicenter, randomized, double-blind, placebo-controlled trial registered with ClinicalTrials.gov on 12 February 2018. Eligible consecutive pregnant women with singleton gestation attending antenatal outpatient clinics will be recruited after receiving counseling and signing the written consent form. Transvaginal cervical length measurement will be performed at recruitment (before 14 + 0 weeks of gestation) and between 18 + 0 and 23 + 6 weeks of gestation. After randomization, women will be randomly assigned to either the treatment group (oral dydrogesterone 10 mg three times daily) or the placebo group, and medication will be started before 14 + 0 weeks of gestation. Assigned groups will be unblinded if the cervical length is ≤ 25 mm between 18 + 0 and 23 + 6 weeks of gestation, and the management option for short cervix will be discussed (oral progesterone, vaginal progesterone, or cervical cerclage). The primary outcome is preterm birth before 37 + 0 weeks of gestation. DISCUSSION: Progesterone is used extensively in part of the in vitro fertilization program as luteal phase support, and it is not associated with teratogenicity. Universal progesterone supplementation may be a better approach to prevent preterm birth. This large, multicenter, randomized, double-blind, placebo-controlled trial will provide the best evidence, leading to the best strategy for the prevention of preterm birth. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03428685. Registered on 12 February 2018.


Assuntos
Medida do Comprimento Cervical/métodos , Intervenção Médica Precoce/métodos , Nascimento Prematuro , Progesterona/administração & dosagem , Tempo para o Tratamento , Adulto , Colo do Útero/diagnóstico por imagem , Método Duplo-Cego , Feminino , Humanos , Estudos Multicêntricos como Assunto , Gravidez , Nascimento Prematuro/diagnóstico , Nascimento Prematuro/etiologia , Nascimento Prematuro/prevenção & controle , Progesterona/efeitos adversos , Progestinas/administração & dosagem , Progestinas/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto
9.
Expert Rev Clin Pharmacol ; 13(2): 163-182, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31975619

RESUMO

Introduction: Steroid hormones are responsible for specific changes in the endometrium during the menstrual cycle, when they are sequentially secreted and, because of this, in the early days sequential combined oral contraceptive regimens were utilized. The same basic concept has been utilized with multi-phasic regimens, in order to produce endometrial pictures mimicking the normal cycle.Areas covered: The Endometrial effects of progestins and estrogens; combined monophasic high- (50 µg), medium- (30 µg), low- (20 µg), ultralow- (15 µg) estrogen content; sequential regimens; multiphasic combinations; treatment schedules.Cervical effects of combined high-dose and sequential combinations, including evidence for an increase in malignant lesions.Expert opinion: Overall, combined oral contraceptives (COCs) inhibit normal proliferative changes and the endometrium becomes thin, narrow, with widely spaced glands and pre-decidual changes in the stroma. During the first few cycles the progestin induces a coexistence of proliferative and secretory features; with time, the picture changes because the progestin induces a down-regulation of estrogen receptors, resulting in tortuous glands similar to those in the secretory phase, but characterized by a quiescent, atrophic glandular epithelium.In the cervical epithelium, under the influence of high-dose COCs, endocervical glands became hypersecretory and in some instances, distinctive type of atypical polypoid endocervical hyperplasia is found.


Assuntos
Anticoncepcionais Orais Combinados/administração & dosagem , Estrogênios/administração & dosagem , Progestinas/administração & dosagem , Animais , Colo do Útero/efeitos dos fármacos , Colo do Útero/metabolismo , Anticoncepcionais Orais Combinados/efeitos adversos , Anticoncepcionais Orais Combinados/farmacologia , Relação Dose-Resposta a Droga , Endométrio/efeitos dos fármacos , Endométrio/metabolismo , Epitélio/efeitos dos fármacos , Epitélio/metabolismo , Estrogênios/efeitos adversos , Estrogênios/farmacologia , Feminino , Humanos , Progestinas/efeitos adversos , Progestinas/farmacologia
10.
Curr Allergy Asthma Rep ; 20(1): 4, 2020 01 28.
Artigo em Inglês | MEDLINE | ID: mdl-31993777

RESUMO

PURPOSE OF REVIEW: Progestogen hypersensitivity (PH) is a condition which typically occurs in women in childbearing years with a spectrum of symptoms ranging from urticaria with or without angioedema, dermatitis to systemic anaphylaxis. Herein, a clinical case of PH is presented followed by a discussion on the evaluation, diagnosis, and management of PH. RECENT FINDINGS: Progestogen hypersensitivity (a.k.a. "autoimmune progesterone dermatitis") symptoms are associated with exogenous progestin exposure (e.g., contraceptive medicines, in vitro fertilization therapy) or endogenous progesterone from progesterone surges during the luteal phase of the menstrual cycle and pregnancy. This condition can be difficult to recognize due to its heterogeneous clinical presentation. The mechanism of PH is believed to be primarily IgE-mediated; however, less commonly other immune responses may be involved. There is now a useful progesterone specific IgE immunoassay to assist in diagnosis and well-defined treatment algorithms that can be used to successfully manage PH. The epidemiology of PH is still poorly elucidated but is likely to be encountered by clinicians and especially allergists given the extensive use of oral contraceptives and increased use of supra-physiologic doses of progesterone required to support pregnancy in IVF. Including PH in the differential diagnosis of women presenting with cyclic hypersensitivity will accelerate diagnosis and successful management of this condition.


Assuntos
Anafilaxia/induzido quimicamente , Doenças Autoimunes/induzido quimicamente , Dispositivos Intrauterinos Medicados/efeitos adversos , Progesterona/efeitos adversos , Progestinas/efeitos adversos , Urticária/induzido quimicamente , Anafilaxia/diagnóstico , Anafilaxia/tratamento farmacológico , Antialérgicos/uso terapêutico , Doenças Autoimunes/diagnóstico , Doenças Autoimunes/tratamento farmacológico , Dermatite/diagnóstico , Dermatite/tratamento farmacológico , Dessensibilização Imunológica , Remoção de Dispositivo , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Imunoglobulina E/sangue , Omalizumab/uso terapêutico , Urticária/diagnóstico , Urticária/tratamento farmacológico , Adulto Jovem
11.
Environ Toxicol Pharmacol ; 74: 103305, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31790957

RESUMO

Glycogen and lipid disruptions represent a spectrum of metabolic disorders that are crucial risk factors for cardiovascular disease in estrogen-progestin oral contraceptive (COC) users. l-glutamine (GLN) has been shown to exert a modulatory effect in metabolic disorders-related syndromes. We therefore hypothesized that GLN supplementation would protect against myocardial and renal glycogen-lipid mishandling in COC-treated animals by modulation of Glucose-6-phosphate dehydrogenase (G6PD) and xanthine oxidase (XO) activities. Adult female Wistar rats were randomly allotted into control, GLN, COC and COC + GLN groups (six rats per group). The groups received vehicle (distilled water, p.o.), GLN (1 g/kg), COC containing 1.0 µg ethinylestradiol plus 5.0 µg levonorgestrel and COC plus GLN respectively, daily for 8 weeks. Data showed that treatment with COC led to metabolically-induced obesity with correspondent increased visceral and epicardial fat mass. It also led to increased plasma, myocardial and renal triglyceride, free fatty acid, malondialdehyde (MDA), XO activity, uric acid content and decreased glutathione content and G6PD activity. In addition, COC increased myocardial but not renal glycogen content, and increased myocardial and renal glycogen synthase activity, increased plasma and renal lactate production and plasma aspartate transaminase/alanine aminotransferase (AST/ALT) ratio. However, these alterations were attenuated when supplemented with GLN except plasma AST/ALT ratio. Collectively, the present results indicate that estrogen-progestin oral contraceptive causes metabolically-induced obesity that is accompanied by differential myocardial and renal metabolic disturbances. The findings also suggest that irrespective of varying metabolic phenotypes, GLN exerts protection against cardio-renal dysmetabolism by modulation of XO and G6PD activities.


Assuntos
Anticoncepcionais Orais Hormonais/efeitos adversos , Estrogênios/efeitos adversos , Glutamina/administração & dosagem , Miocárdio/química , Obesidade/prevenção & controle , Progestinas/efeitos adversos , Animais , Colágeno/metabolismo , Anticoncepcionais Orais Hormonais/administração & dosagem , Estrogênios/administração & dosagem , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Glucosefosfato Desidrogenase/metabolismo , Glutamina/farmacologia , Metabolismo dos Lipídeos/efeitos dos fármacos , Modelos Animais , Obesidade/induzido quimicamente , Progestinas/administração & dosagem , Distribuição Aleatória , Ratos , Ratos Wistar , Xantina Oxidase/metabolismo
12.
BMJ Sex Reprod Health ; 46(2): 139-146, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31754066

RESUMO

INTRODUCTION: There is unmet need for male contraceptive options, but a recent injectable combination male contraceptive trial was terminated early due to adverse events (AEs). METHODS: We examined the frequency of reported AEs by male research participants compared with AEs reported in prescribing information of approved female hormonal contraceptive methods. Published data from trials of the top five most-used female hormonal contraceptives, supplemented by contemporary contraceptive research, were compared with the frequency of AEs reported in a male injectable hormonal contraceptive trial. RESULTS: We observed similar frequencies of AEs reported by users of male contraceptives compared with those reported by female users. Among quantitatively comparable AEs, compared with men, women reported experiencing higher frequencies of headaches, pelvic pain, and weight gain and similar frequencies of decreased libido. Compared with women, men reported experiencing higher frequencies of acne and mood changes. Men discontinued participation due to AEs at a lower frequency than women. CONCLUSIONS: Female hormonal methods generally have similar frequencies of AEs to those reported in a recent male hormonal contraceptive trial, and male users had lower rates of discontinuation due to AEs. There were fewer serious AEs of the male contraceptive than reported in contemporary female trials which resulted in FDA licensure. This suggests there may be implicit bias in the scientific community regarding the level of acceptable risk for users of male contraceptive methods.


Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Contracepção Hormonal/normas , Segurança do Paciente/normas , Acne Vulgar/epidemiologia , Acne Vulgar/etiologia , Adulto , Anticoncepcionais Masculinos/normas , Anticoncepcionais Masculinos/uso terapêutico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Cefaleia/epidemiologia , Cefaleia/etiologia , Contracepção Hormonal/métodos , Humanos , Levanogestrel/efeitos adversos , Levanogestrel/uso terapêutico , Libido/efeitos dos fármacos , Masculino , Transtornos do Humor/epidemiologia , Transtornos do Humor/etiologia , Segurança do Paciente/estatística & dados numéricos , Dor Pélvica/epidemiologia , Dor Pélvica/etiologia , Progestinas/efeitos adversos , Progestinas/uso terapêutico , Ganho de Peso/efeitos dos fármacos
13.
Am J Perinatol ; 37(2): 127-136, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31652479

RESUMO

BACKGROUND: Women with a history of spontaneous preterm birth (SPTB) are at a significantly increased risk for recurrent preterm birth (PTB). To date, only one large U.S. clinical trial comparing 17-OHPC (17-α-hydroxyprogesterone caproate or "17P") to placebo has been published, and this trial was stopped early due to a large treatment benefit. OBJECTIVE: This study aimed to assess whether 17-OHPC decreases recurrent PTB and neonatal morbidity in women with a prior SPTB in a singleton gestation. STUDY DESIGN: This was a double-blind, placebo-controlled international trial involving women with a previous singleton SPTB (clinicaltrials.gov: NCT01004029). Women were enrolled at 93 clinical centers (41 in the United States and 52 outside the United States) between 160/7 to 206/7 weeks in a 2:1 ratio, to receive either weekly intramuscular (IM) injections of 250 mg of 17-OHPC or an inert oil placebo; treatment was continued until delivery or 36 weeks. Co-primary outcomes were PTB < 35 weeks and a neonatal morbidity composite index. The composite included any of the following: neonatal death, grade 3 or 4 intraventricular hemorrhage, respiratory distress syndrome, bronchopulmonary dysplasia, necrotizing enterocolitis, or proven sepsis. A planned sample size of 1,707 patients was estimated to provide 98% power to detect a 30% reduction in PTB < 35 weeks (30% to 21%) and 90% power to detect a 35% reduction in neonatal composite index (17%-11%) using a two-sided type-I error of 5%. Finally, this sample size would also provide 82.8% power to rule out a doubling in the risk of fetal/early infant death assuming a 4% fetal/early infant death rate. Analysis was performed according to the intention-to-treat principle. RESULTS: Baseline characteristics between the 1,130 women who received 17-OHPC and 578 women who received placebo were similar. Overall, 87% of enrolled women were Caucasian, 12% had >1 prior SPTB, 7% smoked cigarettes, and 89% were married/lived with partner. Prior to receiving study drug, 73% women had a transvaginal cervical length measurement performed and <2% had cervical shortening <25 mm. There were no significant differences in the frequency of PTB < 35 weeks (17-OHPC 11.0% vs. placebo 11.5%; relative risk = 0.95 [95% confidence interval (CI): 0.71-1.26]) or neonatal morbidity index (17-OHPC 5.6% vs. placebo 5.0%; relative risk = 1.12 [95% CI: 0.68-1.61]). There were also no differences in frequency of fetal/early infant death (17-OHPC 1.7% vs. placebo 1.9%; relative risk = 0.87 [95% CI: 0.4-1.81]. Maternal outcomes were also similar. In the subgroup of women enrolled in the United States (n = 391; 23% of all patients), although the rate of PTB < 35 weeks was higher than the overall study population, there were no statistically significant differences between groups (15.6% vs. 17.6%; relative risk = 0.88 [95% CI: 0.55, 1.40]. CONCLUSION: In this study population, 17-OHPC did not decrease recurrent PTB and was not associated with increased fetal/early infant death.


Assuntos
Caproato de 17 alfa-Hidroxiprogesterona/uso terapêutico , Doenças do Recém-Nascido/prevenção & controle , Resultado da Gravidez , Nascimento Prematuro/prevenção & controle , Progestinas/uso terapêutico , Caproato de 17 alfa-Hidroxiprogesterona/efeitos adversos , Método Duplo-Cego , Feminino , Idade Gestacional , Humanos , Recém-Nascido , Doenças do Recém-Nascido/epidemiologia , Injeções Intramusculares , Morte Perinatal , Gravidez , Complicações na Gravidez/epidemiologia , Progestinas/efeitos adversos , Prevenção Secundária , Falha de Tratamento
14.
Am J Epidemiol ; 189(4): 314-329, 2020 04 02.
Artigo em Inglês | MEDLINE | ID: mdl-31665225

RESUMO

We investigated the influence of premenopausal use of progestogens on melanoma using data from E3N (Etude Epidémiologique Auprès de Femmes de l'Education Nationale), a prospective cohort of 98,995 French women, aged 40-65 years at inclusion. We used Cox models to adjust for age and melanoma risk factors. Over 1992-2008, 540 melanoma cases were ascertained among 79,558 women. We found a modest association between self-reported progestogen use and melanoma risk (hazard ratio (HR) = 1.23, 95% confidence interval (CI) = 1.02, 1.47), which was reduced after adjustment for melanoma risk factors (HR = 1.15, 95% CI: 0.95, 1.39). There was no heterogeneity across types of progestogens (P = 0.22), and use of multiple progestogens was positively associated with melanoma risk (HR = 1.33, 95% CI: 1.04, 1.70). Among users, we found no relationship with duration of progestogen use, age at start and last use, and time since first and last use. Although our results did not show evidence of a confounding effect of sun exposure, progestogen users had lower levels of residential sun exposure and were more likely to report sunscreen use, suggesting specific sun exposure profiles in users. Our findings do not support a strong influence of progestogens on melanoma risk. Further research is needed to confirm these results.


Assuntos
Melanoma/epidemiologia , Progestinas/efeitos adversos , Neoplasias Cutâneas/epidemiologia , Adulto , Idoso , Feminino , França/epidemiologia , Humanos , Melanoma/induzido quimicamente , Pessoa de Meia-Idade , Pré-Menopausa , Progestinas/administração & dosagem , Estudos Prospectivos , Neoplasias Cutâneas/induzido quimicamente
15.
Ceska Gynekol ; 85(3): 222-225, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33562977

RESUMO

Methods of hormonal contraception are an important tool in the implementation of family planning. Although the primary design of hormonal contraceptives was based on a combination of estrogenic and progestogenic components, the most important component of hormonal contraceptives is the progestin molecule responsible for the anti-gonadotropic effect leading to ovulation inhibition, increased cervical mucus viscosity and endometrial desynchronization. The combination of progestins with estrogens has improved the bleeding profile, but it has increased the risk of cardiovascular complications, particularly deep venous thrombosis and pulmonary embolism, in patients at specific risk. The development of purely progestogenic contraceptives is being conducted to eliminate these cardiovascular risks. A new hormonal contraceptive based on oral drospirenone alone at a daily dose of 4 mg administered in a 24-active tablet + 4 days hormone-free interval shows contraceptive efficacy and bleeding profile consistent with combined hormonal contraceptives and high safety profile as the risk of deep vein thrombosis and pulmonary embolism does not increase according to recent clinical studies. It appears to be a very effective alternative to combination products suitable for a wide range of users.


Assuntos
Anticoncepção , Anticoncepcionais Orais Hormonais , Anticoncepcionais Orais Hormonais/efeitos adversos , Estrogênios , Feminino , Humanos , Progestinas/efeitos adversos
16.
Presse Med ; 48(11 Pt 1): 1269-1283, 2019 Nov.
Artigo em Francês | MEDLINE | ID: mdl-31757732

RESUMO

Hypertension is a major risk factor for cardiovascular diseases. Because of the high frequency of hormonal contraceptives use, assessing their side effects is an important public health issue. In this perspective, we conducted a review of the risk of hypertension associated with the use of hormonal contraceptives, either combined estrogen-progestin or only progestin. The use of combined hormonal contraceptives, regardless of its type and route of administration, is associated with a slight increase in blood pressure, both systolic and diastolic blood pressures. The frequency of onset of hypertension in women who use combined hormonal contraception is between 0.6% and 8.5%. Progestin-only contraception seems safe with respect to the risk of hypertension. It is therefore important to remember that the use of combined hormonal contraception is contra-indicated in hypertensive women, even well controlled. Finally, we propose a prescription assistance algorithm according to the recommendations of an expert panel. It should be remembered that taking blood pressure at each contraceptive consultation (initial and follow-up) is essential.


Assuntos
Anticoncepção/efeitos adversos , Anticoncepcionais Orais Combinados/efeitos adversos , Anticoncepcionais Orais Hormonais/efeitos adversos , Hipertensão/induzido quimicamente , Progestinas/efeitos adversos , Adolescente , Adulto , Pressão Sanguínea/efeitos dos fármacos , Determinação da Pressão Arterial , Feminino , Humanos , Pessoa de Meia-Idade , Progestinas/administração & dosagem , Fatores de Risco , Adulto Jovem
17.
Medicina (Kaunas) ; 55(9)2019 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-31480288

RESUMO

Background and Objectives: Hormonal replacement therapy (HRT) is effective in treating many debilitating symptoms of menopause. However, its use in women with uterine fibroids is widely debated, based on the susceptibility of these tumors to sexual steroids. This review aims to ascertain the effects of HRT on leiomyomas development and growth in postmenopausal women. Materials and Methods: Electronic databases (i.e., MEDLINE, Scopus, ClinicalTrials.gov, EMBASE, Sciencedirect, the Cochrane Library at the CENTRAL Register of Controlled Trials, Scielo) were searched from January 1990 until May 2019. All English-written studies evaluating the impact of various HRT regimens on uterine leiomyomas were selected. Results: Seventeen papers, considering a total of 1122 participants, were included. Fifteen of these were prospective trials, of which nine were randomized controlled trials. The remaining two works were a retrospective observational trial and a retrospective case series respectively. Five studies evaluated the effects of tibolone, also comparing it with various estrogen/progestin combinations, while two were about raloxifene. Thirteen studies compared different combinations of estrogens/progestins, the most common being transdermal estrogens (used in nine studies) and medroxyprogesterone acetate at different doses (used in 10 studies). Conclusions: For women with uterine fibroids, the choice of the most appropriate HRT regimen is crucial to avoid leiomyomas growth and the symptoms possibly related to it. Available data are conflicting, but suggest that uterine fibroids might be influenced by HRT, without representing an absolute contraindication to hormonal replacement therapy. Women with uterine fibroids subjected to HRT should be periodically examined and hormonal treatment should be discontinued if leiomyomas appear to increase in size. Moreover, the minimal effective dose of progestin should be employed.


Assuntos
Terapia de Reposição de Estrogênios/efeitos adversos , Leiomioma/fisiopatologia , Progestinas/farmacologia , Neoplasias Uterinas/fisiopatologia , Progressão da Doença , Estrogênios/efeitos adversos , Estrogênios/farmacologia , Feminino , Humanos , Leiomioma/diagnóstico por imagem , Leiomioma/tratamento farmacológico , Pós-Menopausa , Progestinas/efeitos adversos , Ultrassonografia , Neoplasias Uterinas/diagnóstico por imagem , Neoplasias Uterinas/tratamento farmacológico , Útero/efeitos dos fármacos
18.
Anticancer Res ; 39(9): 4897-4903, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31519593

RESUMO

BACKGROUND/AIM: Endometrial hyperplastic polyps (EHP) may progress to endometrial carcinoma (EC) if left untreated. We aimed to prospectively investigate the efficacy of the low-dose levonorgestrel intrauterine system (LNG-IUS) as therapy for EHP with malignant potential. PATIENTS AND METHODS: In total, 37 women with EHP underwent therapy with LNG-IUS containing 13.5 mg levonorgestrel for six months or 4-10 weeks depending on whether the EHP was characterized (by D-score analysis) as low- to medium-risk (n=33) or high-risk (n=4) of coexistent or future EC. Therapy response was defined as complete clearance of hyperplastic glands in post-therapy endometrial biopsy. RESULTS: All women with low- to medium-risk EHP obtained therapy response, whereas only 1 out of 4 with high-risk EHP responded to therapy. None of the women were diagnosed with EC during the study and no serious adverse events occurred. CONCLUSION: Low-dose LNG-IUS represents a promising therapy for selected women with EHP.


Assuntos
Antineoplásicos Hormonais/administração & dosagem , Hiperplasia Endometrial/tratamento farmacológico , Hiperplasia Endometrial/patologia , Pólipos/patologia , Lesões Pré-Cancerosas/tratamento farmacológico , Lesões Pré-Cancerosas/patologia , Progestinas/administração & dosagem , Adulto , Idoso , Biomarcadores , Feminino , Humanos , Pessoa de Meia-Idade , Projetos Piloto , Progestinas/efeitos adversos , Estudos Prospectivos , Resultado do Tratamento
19.
Obstet Gynecol ; 134(3): 581-589, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31403601

RESUMO

OBJECTIVE: To assess fracture risk among women with depot medroxyprogesterone acetate (DMPA), oral contraceptive pill (OCP), and intrauterine device (IUD) use. METHODS: A retrospective cohort study of 308,876 women age 12-45 years who initiated DMPA, combined or progestin-only OCPs, and copper and levonorgestrel IUDs from 2005 to 2015. Cumulative DMPA, OCP, and IUD use was assessed. Time since last DMPA injection was quantified as recent (within 2 years) and past (more than 2 years ago). Crude fracture rate was estimated using a Poisson distribution. Unadjusted and adjusted hazard ratios (HRs) were estimated using cox proportional hazards models. RESULTS: Thirteen percent of women used DMPA, 78.6% combined OCPs, 17.4% progestin-only OCPs, and 26.2% IUDs; 29.5% used more than one method. There were 7,659 fractures in 1,391,251 person-years (5.5/1,000 person-years [95% CI 5.4-5.6]). The fracture rate for women with any DMPA use was 6.6 (95% CI 6.1-7.2) and 7.8 (95% CI 6.0-10.0) for women with recent use and more than 2 years of cumulative use. Women who had recent use with 2 years or less, or more than 2 years of cumulative use had higher fracture risk compared with women who had no DMPA use and used other methods (adjusted HR 1.15 [95% CI 1.01-1.31] and 1.42 [95% CI 1.10-1.83], respectively). Fracture risk was not increased in women with past DMPA use. Women who had more than 2 years cumulative use of combined OCPs and women with any progestin-only OCP use had lower fracture risk compared with women who did not use OCPs and used other methods (adjusted HR 0.85 [95% CI 0.76-0.96] and 0.88 [95% CI 0.80-0.97], respectively). CONCLUSION: Use of DMPA beyond 2 years should not be considered an absolute contraindication. Although DMPA use was associated with slightly increased fracture risk compared with other methods, the absolute risk of fracture was small and was not observed after discontinuation.


Assuntos
Anticoncepcionais Femininos/efeitos adversos , Anticoncepcionais Orais/efeitos adversos , Fraturas Ósseas/induzido quimicamente , Dispositivos Intrauterinos Medicados/efeitos adversos , Acetato de Medroxiprogesterona/efeitos adversos , Adolescente , Adulto , Criança , Feminino , Humanos , Levanogestrel/efeitos adversos , Pessoa de Meia-Idade , Progestinas/efeitos adversos , Estudos Retrospectivos , Fatores de Risco , Adulto Jovem
20.
PLoS One ; 14(7): e0218511, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31276521

RESUMO

BACKGROUND: Use of hormonal contraceptives has been associated with Staphylococcus aureus nasal carriage in adult women. However, the role of hormonal contraceptives in S. aureus colonization among adolescents and associations with progestin only contraceptives are unknown. METHODS: We obtained nasal and throat swab samples from 439 girls aged 17-21 years in the population-based Tromsø study Fit Futures, 2012-2013, Norway, with information on lifestyle, health and biomarkers. We used multivariable logistic regression to study the association between use of hormonal contraceptives and Staphylococcus aureus carriage while adjusting for potential confounding factors. RESULTS: Staphylococcus aureus nasal carriage prevalence were 34%, 42%, and 61% among progestin-only users, non-users, and progestin-estrogen combination contraceptive users, respectively (P<0.001). Use of combination contraceptives doubled the odds of nasal carriage (non-users reference; OR = 2.31, 95%CI = 1.43-3.74). The OR of nasal carriage was 0.29 among progestin-only users compared to combination contraceptives users (95% CI = 0.12-0.67). DISCUSSION: In this study, use of combination hormonal contraceptives was associated with higher risk of Staphylococcus aureus nasal carriage in adolescent girls. Experimental design studies are needed to establish the role of exogenous sex steroids in Staphylococcus aureus colonization in women.


Assuntos
Comportamento Contraceptivo , Anticoncepcionais Orais Hormonais/administração & dosagem , Estrogênios , Cavidade Nasal/microbiologia , Faringe/microbiologia , Progestinas , Staphylococcus aureus , Adolescente , Adulto , Estrogênios/administração & dosagem , Estrogênios/efeitos adversos , Feminino , Humanos , Noruega/epidemiologia , Prevalência , Progestinas/administração & dosagem , Progestinas/efeitos adversos , Fatores de Risco , Infecções Estafilocócicas/induzido quimicamente , Infecções Estafilocócicas/epidemiologia , Staphylococcus aureus/crescimento & desenvolvimento , Staphylococcus aureus/isolamento & purificação , Adulto Jovem
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