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Contraceptive use in acne
Abstract
Acne vulgaris is an inflammatory disorder of the pilosebaceous follicle. It is well established that androgen hormones play a major role in sebum production and excretion, and are vital in the pathogenesis of acne. Isotretinoin notwithstanding, hormonal therapies such as combined oral contraceptives (COCs) and spironolactone are the only treatments that can affect sebum production and the androgen component of acne. Contraceptives are also used during isotretinoin therapy for pregnancy prevention. It is important for a dermatologist to be familiar with all the available methods of contraception to provide essential counseling to patients. The aim of this paper is to review the role of hormones in acne pathogenesis, discuss the use of hormonal therapies for acne, and detail various alternative contraceptive methods in relation to isotretinoin treatment and pregnancy prevention.
... It is necessary to identify risks/contradindications for certain conditions (Table 10) associated with COC use. 89 Dosing and administration. Dosing should start on the rst day of menstrual cycle as follows: one tablet daily for 21 days, stop for seven C O N S E N S U S G U I D E L I N E S days, then repeat. ...
... During a woman's reproductive years, her risk for VTE with ethinyl estradiol is 6 to 8 times higher than in nonusers. 89 The evidence regarding COCs and stroke is unclear. In healthy, young women, the risk of ischemic stroke is low, but concomitant COC use and smoking increases the risk signi cantly. ...
... For cervical cancer, there might be an association; however, the association is reduced with cessation of a COC, and, by 10 years, the risk of cervical cancer is similar to that of those who have never taken COCs. 89 Recently, the Singapore Health Promotions Board recommended decreasing cervical screenings to once every three years after the onset of sexual activity or beginning at the age of 25. 91 It is acceptable to start COCs with succeeding consultation that includes a Pap smear. ...
Due to the multiethnic patient population with varying skin types in Singapore, clinicians often find the management of acne in their patients to be challenging. The authors developed these guidelines to provide comprehensive advice on individualized acne treatment and to provide a reference guide for all doctors who treat patients of Asian descent. Unique features of acne in Singapore are highlighted. We address concerns such as diet, special population needs, and the benefits, side effects, risks, and cost-effectiveness of currently available acne treatments. These treatment guidelines outline recommendations for the diagnosis, grading, and treatment of children, adolescents, and adults with acne of varying severity, and include advice pertaining to the use of cosmeceuticals and management of scars.
... The side effects of COCs have been evaluated in millions of women. 18 Overall there are similar mortality rates seen between users and nonusers, but side effects are frequent and differ according to EE dose and progestin type. 19 Common side effects seen with COC use include weight gain, breast tenderness, breakthrough bleeding, and moodiness, all of which are seen less frequently with the newer-generation COCs. ...
... 22,23 There are also many uncommon causes for genetic thrombophilia that increase the risk of VTEs, but these are often first diagnosed when a young woman on COCs experiences her first VTE. 18 Increased risk of both breast and ovarian cancer has been suggested in the literature. However, the risk is marginal and controversial. ...
Therapeutic actives for acne have changed little in the last decade. Recognition that acne is an inflammatory condition, not an infectious one, has led to a call for reduction in antibiotic use, which has culminated in a re-evaluation of our nonantibiotic choices. Spironolactone and oral contraceptives have become more acceptable first-line choices, and earlier use of isotretinoin has been proposed.
... Кроме того, эти эффекты могут быть «замаскированы» приемом этих препаратов по другим показаниям, одновременно препятствуя развитию акне. Однако важно отметить, что в ранее проведенных исследованиях показано, что препараты, содержащие только прогестин, этоногестрел, левоноргестрел могут ухудшить симптоматику акне [18]. ...
... В качестве антиандрогена и потенциального ингибитора себогенеза возможно применение спиронолактона, являющегося возможной альтернативой перорального изотретиноина и КОК, позволяющего снизить риск побочных эффектов при приеме препаратов этих групп [18]. В ряде исследований [19] показана эффективность перорального приема спиронолактона в лечении угревой болезни у женщин среднего возраста. ...
... De ovaria maken testosteron, androsteen dion en DHEA aan. Overigens is er ook ter hoogte van de huid productie van testosteron vanuit acetaat en cholesterol door enzymatische activiteit aanwezig in keratinocyten en sebocyten (3). Voornamelijk DHT zorgt voor de groei van talgklieren en een toename van de talgproductie, de affiniteit voor de androgeenrecep tor is vijf tot tien keer groter dan deze van testosteron. ...
... Het betreft vooral uitgesproken inflammatoire letsels en minder comedonen, vaak ziet men een "flareup" premenstrueel (4). Stan daardtherapie (lokale therapie en antibiotica) biedt vaak geen adequate controle en de meerderheid van de patiënten heeft een normaal gehalte van circule rende androgenen in het bloed (3). ...
Samenvatting Androgenen en oestrogenen spelen een rol in de pathofysiologie van acne. Androgenen, voorna-melijk testosteron en dihydrotestosteron (DHT), verhogen via androgeenreceptoren de sebumpro-ductie. Oestrogenen hebben een gunstig effect op acne door de aanmaak van androgenen en de hoeveelheid vrij testosteron te verminderen. Tevens werken zij als antagonist ter hoogte van de androgeenreceptor. Zo heeft anticonceptie onder de vorm van oestroprogestatieve combinatie-preparaten, voornamelijk als gevolg van de oestrogenencomponent, een gunstige invloed op acne. De synthetische progestagenen werken, naargelang van het type progestageen, als remmer of activator van de androgeenreceptoren, met een gunstig of een ongunstig effect op acne. Een meta-analyse bevestigt dat orale oestroprogestatieve combinatieanticonceptiva als behandeling van acne doeltreffender zijn dan een placebo. Een vergelijking tussen de verschillende preparaten is niet conclusief, waardoor er geen duidelijk superieur progestageen in de behandeling van acne naar voren komt. De vaginale ring en patch zijn dankzij hun oestrogeencomponent mogelijke alter-natieven. De combinatie met de meeste antibiotica heeft geen ongunstig effect op de contracep-tieve veiligheid. Inleiding Acne is een vaak voorkomend huidprobleem. Andro genen en gerelateerde hormoonreceptoren spelen een rol in de pathofysiologie en de behandeling van acne en via deze weg heeft anticonceptie een mogelijke plaats in de behandeling van acne. Deze tekst geeft een kort overzicht over de pathofysiologie van acne en een samenvatting van gegevens uit de literatuur om een gegrond advies te geven over het gebruik van anticonceptie in het kader van de behandeling van acne.
... Spironolactone has an antiandrogenic effect. 6 Spironolactone is a possible alternative to oral ...
Background
Acne or acne vulgaris is the most common chronic inflammatory disease of the sebaceous follicles.
Objectives
The present study aims to identify the main lines of research in the field of acne treatment using reproducible scientometric methods. In this article, we reviewed the following research trends: facial acne, different antibiotics, retinoids, anti-inflammatory drugs, epidermal growth factor receptor inhibitors therapy, and associated diseases.
Methods
The analysis of publications from the PubMed collection was carried out from 1871 to 2022. All data were analyzed using Microsoft Excel. The evolution of the terminological portrait of the disease is shown.
Results
Trends in the use of various groups of antibiotics, retinoids, anti-inflammatory drugs, and photodynamic therapy for acne treatment have been found. There is a growing interest in clindamycin and doxycycline (polynomial and exponential growth, respectively). The effects of isotretinoin are also being studied more frequently (active linear growth). The publication of studies on spironolactone is increasing (linear growth). There is also a steady interest in the use of epidermal growth factor receptor inhibitors in the recent years. There is active research on acne and polycystic ovary syndrome (exponential growth).
Limitations
Only articles in English were selected. The most frequent terms were considered.
Conclusions
The dynamics of publication activity in the field of acne was considered. The aim of the current scientometric study was to analyze the global trends in acne treatments. The trend analysis made it possible to identify the most explored areas of research, as well as indicate those areas in dermatology in which interest is declining.
... 4 The ovaries release estrogen, progesterone, and androstenedione; androstenedione is first converted to testosterone, then to DHT by 5α-reductase. 16 Testosterone and DHT bind to androgen receptors in the pilosebaceous unit 15 ; the androgen-receptor complex dimerizes and translocates to the cell nucleus, 15 where it promotes the expression of genes involved in the production of sebum and inflammatory cytokines. 4,15 Ample evidence supports the role of androgens in acne pathogenesis in both male and female patients. ...
Acne vulgaris is the most common skin condition in the US, affecting up to 50 million Americans. The American Academy of Dermatology (AAD) guidelines on acne treatment were developed to provide recommendations for the diagnosis, grading, and treatment of acne in adolescents and adults to support clinicians in their therapeutic decision-making process. The most recent acne guidelines were published in 2016, and the approach to care and the therapeutic landscape of acne have evolved since that time. The Acne Management Consensus Roundtable was convened in 2022 to discuss unmet needs in the management of acne. The main focus of the meeting was the role of androgens in acne pathology; the evaluation of clascoterone, the first topical anti-androgen that specifically addresses sebum production in acne; and the identification of the place of clascoterone in therapy. Clascoterone was approved by the US Food and Drug Administration for the treatment of acne in patients 12 years and older in 2020. This report aims to highlight important limitations of the 2016 AAD treatment guidelines and to familiarize practitioners with clascoterone and its indication, efficacy and safety profile, and potential use across diverse patient populations. With its new mechanism of action, clascoterone may be able to fulfill important unmet needs in acne treatment. Baldwin H, Farberg AS, Frey C, et al. Unmet needs in the management of acne vulgaris: a consensus statement. J Drugs Dermatol. 2023;22(6):582-587. doi:10.36849/JDD.7587.
... (14) Acne patients also have lower levels of serum estradiol and sex hormone binding globulin, and combined oral contraceptives have been effective in acne patients, supporting the idea that estrogens reduce the function of sebaceous glands. (15,16) However, later studies provide conflicting data, in particular, despite the fact that the expression of α-and β-estrogen receptors in the sebaceous glands has been described, 17β-estradiol and progesterone did not have a noticeable effect on either proliferation or lipid production by SZ95 sebocytes. (17) The search for genotypic markers in patients with varying severity of acne is a difficult task due to the multifactorial pathogenesis and the role of trigger factors in the formation of acne. ...
Background: Acne is a multifactorial disease, in the pathogenesis of which one of the leading factors is the excessive effect of androgens on the hair follicles (HFs) and sebaceous glands (SGs), along with hypersecretion of sebum, pathological follicular hyperkeratosis and an inflammatory response. The search for genotypic markers in patients with varying severity of acne is a difficult task due to the multifactorial pathogenesis and the role of trigger factors in the formation of acne. The aim of this study was to determine SNPs within 3 genes involved in steroidogenesis (MVK, ARPC1B, and CA2) in patients with severe acne.
Methods and Results: The study included 70 patients (42 men and 28 women) aged between 15 and 46 years (the median age - 22.1 years). The main group (MG) included 50 patients (29 men and 21 women) with severe acne. The control group (CG) consisted of 20 apparently healthy individuals (13 men and 7 women). Molecular-genetic diagnostics was carried out by the method of high-throughput DNA sequencing (next-generation sequencing). Our study showed that severe acne is associated with 12 polymorphic loci of the MVK gene (4 SNPs in exons and 8 SNPs in introns), 7 SNPs of the ARPC1B gene (2 SNPs in exons and 5 SNPs in introns), and 9 SNPs of the CA2 gene (3 SNPs in exons and 6 SNPs in introns).
Conclusion: The revealed features of the SNPs within the MVK, ARPC1B, and CA2 genes in patients with severe acne probably indicate a hereditary determination of steroidogenesis in acne.
... Systemic isotretinoin has well-known adverse effects, including mucous and cutaneous adverse effects, elevated live enzymes, dyslipidemia, inflammatory bowel disease, depression, and the most freighting serious adverse effect teratogenicity [20] . Strict contraceptive measure and pregnancy prevention programs must be used in childbearing age women during isotretinoin therapy intake and for a period of at least 1 month after its stoppage [21] . ...
... Также возможен вариант с последующим переходом на прием изотретиноина per os по вышеуказанной рекомендованной схеме постепенного увеличения дозы на 4-й нед терапии системным ГКС [115]. Вопрос о необходимости назначения антиандрогенной терапии, в т. ч. комбинированных оральных контрацептивов девочкам, должен рассматриваться при недостаточном ответе на «стандартную» терапию ВА или при наличии эндокринологических патологий с оценкой возможных нежелательные явлений и соотношения «польза/риск» в каждом конкретном случае [116]. ...
В статье представлены современные данные о патогенезе вульгарных акне (ВА), особенностях клинической картины, диагностике и терапевтической тактике у детей и подростков. Приведены сведения о влиянии наиболее значимых внешних и внутренних факторов на патогенез и риск развития ВА. На основе анализа Европейских методических рекомендаций и рекомендаций Глобального альянса по лечению и диагностике ВА сформированы соответствующие диагностические и терапевтические алгоритмы ведения пациентов. Также продемонстрирована важная роль назначения эффективной терапии в виде фиксированной синергичной комбинации активных веществ, представленных топическим ретиноидом (адапален) и бензоила пероксидом.
... In contrast to the pro-lipogenic actions of androgens, estrogens were originally described to have opposite effects, namely to decrease the proliferation of sebocytes and to inhibit the production of sebum 39,40 . Patients with acne have also been shown to have lower serum estradiol and sex hormone binding globulin levels 41,42 , and combined oral contraceptive therapy has been shown to be beneficial in acne patients 43 , supporting the idea that estrogens decrease the function of the sebaceous gland. However, more recent reports have offered conflicting evidence, since whilst the expression of estrogen receptor -α and -β was described on sebaceous glands 26 , 17β-estradiol 45,46 . ...
The sebaceous gland, long considered an evolutionary relic with little-to-no physiological relevance in humans, has emerged in recent decades as a key orchestrator and contributor to many cutaneous functions. In addition to the classical physico-chemical barrier function of the skin against constant environmental challenges, a more novel, neuro-immune modulatory role has also emerged. As part of the complex intercellular communication network of the integumentary system, the sebaceous gland acts as a “relay station” in the skin for many endocrine factors. This review aims to offer a comprehensive overview of endocrine effects and subsequent interactions on this much maligned mini-organ.
... Androgen receptor antagonists, such as cyproterone acetate and spironolactone can also be used alone, without oestrogen, in patients who cannot take oral contraceptives. [51][52][53][54][55][56] Hormonal therapies predominantly target excess sebum production (but also follicular keratinocyte proliferation), and so need to be used together with topical fixed combination therapy to enable all four acne pathogenic factors to be targeted. 53,55 Maintenance therapy recommendations are the same as for predominant comedonal acne. ...
Background:
Many current guidelines provide detailed evidence-based recommendations for acne treatment.
Objective:
To create consensus-based, simple, easy-to-use algorithms for clinical acne treatment in daily office-based practice and to provide checklists to assist in determining why a patient may not have responded to treatment and what action to take.
Methods:
Existing treatment guidelines and consensus papers were reviewed. The information in them was extracted and simplified according to daily clinical practice needs using a consensus-based approach and based on the authors' clinical expertise.
Results:
As outcomes, separate simple algorithms are presented for the treatment of predominant comedonal, predominant papulopustular and nodular/conglobate acne. Patients with predominant comedonal acne should initially be treated with a topical retinoid, azelaic acid or salicylic acid. Fixed combination topicals are recommended for patients with predominant papulopustular acne with treatment tailored according to the severity of disease. Treatment recommendations for nodular/conglobate acne include oral isotretinoin or fixed combinations plus oral antibiotics in men, and these options may be supplemented with oral anti-androgenic hormonal therapy in women. Further decisions regarding treatment responses should be evaluated 8 weeks after treatment initiation in patients with predominant comedonal or papulopustular acne and 12 weeks after in those with nodular/conglobate acne. Maintenance therapy with a topical retinoid or azelaic acid should be commenced once a patient is clear or almost clear of their acne to prevent the disease from recurring. The principal explanations for lack of treatment response fall into 5 main categories: disease progression, non-drug-related reasons, drug-related reasons, poor adherence, and adverse events.
Conclusion:
This practical guide provides dermatologists with treatment algorithms adapted to different clinical features of acne which are simple and easy to use in daily clinical practice. The checklists to establish the causes for a lack of treatment response and subsequent action to take will facilitate successful acne management.
... It can be used as a sole agent or in combination with an oral contraceptive. 15,16 In addition, there have been many attempts to develop a cosmetic ingredient able to improve oily skin. Vogelgesang and colleagues 17 demonstrated the in vitro and in vivo efficacy of Orthosiphon stamineus leaf extract as a cosmetic ingredient intended to reduce the oily appearance of skin and to improve skin imperfections related to excess sebum. ...
Background:
Enlarged skin pores refer to conditions that present with visible topographic changes of skin surfaces. Although not a medical concern, enlarged pores are a cosmetic concern for a large number of individuals. Moreover, clear definition and possible causes of enlarged pores have not been elucidated.
Objective:
To review the possible causes and treatment options for skin pores.
Methods:
This article is based on a review of the medical literature and the authors' clinical experience in investigating and treating skin pores.
Results:
There are 3 major clinical causes of enlarged facial pores, namely high sebum excretion, decreased elasticity around pores, and increased hair follicle volume. In addition, chronic recurrent acne, sex hormones, and skin care regimen can affect pore size. Given the different possible causes for enlarged pores, therapeutic modalities must be individualized for each patient.
Conclusion:
Potential factors that contribute to enlarged skin pores include excessive sebum, decreased elasticity around pores, and increased hair follicle volume. Because various factors cause enlarged facial pores, it might be useful to identify the underlying causes to be able to select the appropriate treatment.
... Besides these, teratogenicity is the most frightening complication of systemic isotretinoin 8 . Because of this, some form of birth control must be advised to any women of child bearing age who is going to use the drug 9 . ...
Background/objective:
Acne vulgaris is one of the most common diseases of the youth. Systemic isotretinoin is the only drug which acts on all of the etiopathogenic mechanisms of acne. Isotretinoin has some well-known side effects. Besides these, there is a suspicion whether it causes infertility or not. In this study, we aimed to evaluate the effects of systemic isotretinoin on male fertility.
Methods:
Eighty one male patients, who were older than 18 years of age, and had severe or refractory acne vulgaris were included in the study. They were given a total dose of 120 mg/kg of systemic isotretinoin over a period of six months. Before and after the study, the spermiogram parameters of the patients were evaluated to show any possible effect on male fertility. The patients' total testosterone, follicle stimulating hormone and luteinizing hormone levels were also evaluated.
Results:
All of the spermiogram parameters changed positively (p < 0.05). There was no significant change in the hormone levels.
Conclusion:
Systemic isotretinoin has a positive effect on male fertility. Since the hormone levels did not change significantly, this positive effect of isotretinoin is not via the hypothalamic-pituitary-gonadal axis but can be due to its regenerative and proliferative effects on the testes.
Introdução: Os anticoncepcionais hormonais são fármacos constituídos por hormônios, geralmente combinados, estrogênio e progestogênio, ou apenas progestogênio. Devido às propriedades características desses hormônios, são também responsáveis por diversos efeitos colaterais, o que tem levado a uma evolução contínua das formulações e tem-se observado vários benefícios não contraceptivos à saúde da mulher. Objetivo: O objetivo dessa revisão foi analisar os usos não contraceptivos dos anticoncepcionais hormonais, evidenciando sua eficácia e segurança. Metodologia: A pesquisa foi realizada em bases de dados eletrônicos e portais de busca, priorizando materiais publicados na faixa anual de 2008 a 2018, sendo encontrados 332 e utilizados 148 materiais de estudo. Resultados: Esses fármacos tem sido uma alternativa eficaz de tratamento da síndrome do ovário policístico, uma vez que reduzem os androgênios circulantes e induzem a melhora dos sintomas como acne, irregularidade menstrual e dismenorreia. Estão associados ao tratamento da endometriose e à menor incidência de câncer de ovário, exercendo um efeito protetor durante anos, até mesmo após a interrupção. Conclusão: Assim, os anticoncepcionais hormonais têm representado uma nova proposta terapêutica simples, segura e eficaz, e seus benefícios ultrapassam os riscos associados, proporcionando uma terapia adequada e individualizada para cada mulher. Non-contraceptive uses of hormonal contraceptive drugs: a review
Purpose of review:
Polycystic ovary syndrome (PCOS) is the most common endocrine disorder among reproductive-age women, the most common cause of infertility among women and a major contributor to pregnancy complications.
Recent findings:
Diagnostic and associated features of PCOS, including hyperandrogenism, insulin resistance, and obesity, contribute to the 2-4-fold increased risk of pregnancy-induced hypertension and preeclampsia, gestational diabetes and preterm birth observed among pregnant women with PCOS. PCOS should be diagnosed according to the 2018 International Guideline. Screening for and optimizing management of hypertension, impaired glucose tolerance and obesity in the preconception window in women with PCOS provides an opportunity to increase the odds of a spontaneous pregnancy, live birth with fertility treatment and possibly reduce the risk of pregnancy complications.
Summary:
Providers should prioritize individualizing recommendations for preconception health optimization in women with PCOS in order to maximize the chance of conception, a healthy pregnancy and the health of future generations.
Contraceptives that contain estrogen and/or progestins are used by millions of women around the world to prevent pregnancy. Owing to their unique physiological mechanism of action, many of these medications can also be used to prevent cancer and treat multiple general medical conditions that are common in women. We performed a comprehensive literature search. This article will describe the specific mechanisms of action and summarize the available data documenting how hormonal contraceptives can prevent ovarian and uterine cancer and be used to treat women with a variety of gynecological and nongynecological conditions such as endometriosis, uterine fibroids, heavy menstrual bleeding, polycystic ovary syndrome, acne, and migraines. Contraceptive methods containing estrogen and progestin can be used for a wide variety of medical issues in women.
Background The management of acne in adult females is problematic, with many having a history of treatment
failure and some having a predisposition to androgen excess. Alternatives to oral antibiotics and combine d oral
contraceptives (COCs) are required.
Objective Our aim was to conduct a hybrid systematic review of the evidence for benefits and potential harms of oral spironolactone in the management of acne in adult females.
Methods The review was conducted according to a previously published protocol. Three reviewers independently selected relevant studies from the search results, extracted data, asse ssed the risk of bias, and rated the quality of the evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.
Results Ten randomized controlled trials (RCTs) and 21 case series were retrieved. All trials were assessed as being at a ‘high risk’ of bias, and the quality of evidence was rated as low or very low for all outcomes. Apart from one crossover trial that demonstrated statistical superiority of a 200 mg daily dose versus inflamed lesions compared with placebo, data from the remaining trials were unhelpful in establishing the degree of effica cy of lower doses versus active com parators or placebo. Menstrual side effects were significantly more common with the 200 mg dose; frequency could be significantly reduced by concomitant use of a COC. Pooling of results for serum potassium supported the recent recommendation that routine monitoring is not required in this patient population.
Conclusion This systematic review of RCTs and case series identified evidence of limited quality to underpin the expert endorsement of spironolactone at the doses typically used (B100 mg/day) in everyday clinical practice
Introduction:
Though typically found in adolescents, acne frequently affects the adult population. In Portugal, no representative studies about acne prevalence in greater populational areas are known. This study had the following objectives: calculate acne prevalence in primary healthcare patients; its characteristics, including risk factors for onset and worsening; collect information concerning selfmedication and/or prescribed treatment.
Material and methods:
Application of a questionnaire and physical examination into a convenience sample, composed by adults from20 - 60 years old that visited, in random days, five primary healthcare centers of the Greater Porto area.
Results:
From the 1,055 evaluated adults, acne prevalence was estimated at 61.5%. Only 36.8% of acne suffering adults was awareof their condition. More than half of tobacco users (62.3%) had acne. Just 25% of acne sufferers sought treatment. The most affected areas were the malars, differing from the younger disease form.
Discussion:
Acne prevalence was relatively higher than other studies. The results of this study have confirmed that acne seems to be related with increased calorie intake, tobacco smoking, whole milk and fat-reduced milk consumption, hirsutism, alopecia and seborrhea.
Conclusion:
In the primary healthcare set, more than half of adults were acne sufferers. These numbers show how important primary healthcare services can be in preventing and intervening when managing acne-related risk factors and psychosocial consequences.
Oral isotretinoin is unrivalled in efficacy and remission capability for treatment of acne. In addition to appropriate monitoring and continued vigilance for safety concerns, appropriate dosing to mitigate avoidable dose-dependent adverse effects is the responsibility of prescribers. Low-dose regimens are better tolerated and effective in inducing acne clearance. Although much progress has been made since the advent of isotretinoin, there remain many unanswered questions regarding optimization to maximize response while minimizing the potential for avoidable adverse events. The ongoing availability of isotretinoin is imperative to patients with acne, their caregivers, and physicians.
Hirsutism, acne, and androgenetic alopecia are classically considered signs of cutaneous hyperandrogenism (CHA). These common skin findings have significant impacts on the quality of patients' lives and pose the diagnostic challenge of excluding underlying disorders. Many with CHA have normal serum androgen levels. Hirsutism is more strongly associated with hyperandrogenism than are acne or androgenetic alopecia. Variable association of CHA with hyperandrogenemia results from the complexity of the underlying pathophysiology, including factors local to the pilosebaceous unit. CHA often occurs in the setting of polycystic ovary syndrome, the most common disorder of hyperandrogenism, but can also present in uncommon conditions, including nonclassic adrenal hyperplasia and androgen-producing tumors. A thorough history and full skin examination are important to guide appropriate diagnostic evaluation. Oral contraceptive pills with or without antiandrogens can provide therapeutic benefit for hirsutism and acne. Medical options for androgenetic alopecia remain limited. Multidisciplinary approaches may be needed given endocrine, metabolic, reproductive, and psychiatric disorders associated with CHA. More high-quality studies into the mechanisms of CHA and the benefits of antiandrogenic therapies are needed. We provide an evidence-based review of key diagnostic and therapeutic considerations in the treatment of women with CHA.
Copyright © 2015 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.
Acne occurs because the sebaceous glands are overstimulated by high levels of androgens or are hypersensitive to normal levels of testosterone. In women with mild or moderate acne, the association of norgestimate (NG), and ethinyl estradiol (EE) is an effective treatment. This is related to the effect of oral contraceptives on androgen production and transport and the antiandrogenic properties of NG itself.
The present work was undertaken to find out whether NG and its derivative, 17-deacetylnorgestimate(dNG), present steroid activities other than antiandrogen activities, using human progesterone receptor(PR), estrogen receptor α(ERα) and β(ERβ), glucocorticoid receptor(GR) and mineralocorticoid receptor(MR)-responsive cell lines.
We confirmed that NG and its metabolite were progestogen partial agonists (EC50 of 13 and 11.1 nM) and ERα selective agonists (EC50 of 30.4 and 43.4 nM), as well as full antagonists of low affinity for GR (IC50 of 325 and 255 nM) and moderate affinity for MR (IC50 of 81.2 and 83.7).
We demonstrated that NG and dNG have full progestogen and weak estrogenic (through ERα) properties, which could explain in part the efficacy of NG in association with EE for the treatment of moderate acne in women. Moreover, their antagonist MR activity might have a favorable impact on cardiovascular risk, atherosclerosis and lipid profiles.
Acne pathogenesis is a multifactorial process that occurs at the level of the pilosebaceous unit. While acne was previously perceived as an infectious disease, recent data have clarified it as an inflammatory process in which Propionibacterium acnes and innate immunity play critical roles in propagating abnormal hyperkeratinization and inflammation. Alterations in sebum composition, and increased sensitivity to androgens, also play roles in the inflammatory process. A stepwise approach to acne management utilizes topical agents for mild to moderate acne (topical retinoid as mainstay ± topical antibiotics) and escalation to oral agents for more resistant cases (oral antibiotics or hormonal agents in conjunction with a topical retinoid or oral isotretinoin alone for severe acne). Concerns over antibiotic resistance and the safety issues associated with isotretinoin have prompted further research into alternative medications and devices for the treatment of acne. Radiofrequency, laser, and light treatments have demonstrated modest improvement for inflammatory acne (with blue-light photodynamic therapy being the only US FDA-approved treatment). However, limitations in study design and patient follow-up render these modalities as adjuncts rather than standalone options. This review will update readers on the latest advancements in our understanding of acne pathogenesis and treatment, with emphasis on emerging treatment options that can help improve patient outcomes.
To test whether use of combined oral contraceptives containing third generation progestogens is associated with altered risk of venous thromboembolism.
Matched case-control study.
10 centres in Germany and United Kingdom.
Cases were 471 women aged 16-44 who had a venous thromboembolism. Controls were 1772 women (at least 3 controls per case) unaffected by venous thromboembolism who were matched with corresponding case for age and for hospital or community setting.
Odds ratios derived with stratified analyses and unconditional logistic regression to adjust for potential confounding variables.
Odds ratios (95% confidence intervals) for venous thromboembolism were: for any oral contraceptives versus no use, 4.0 (3.1 to 5.3); for second generation products (low dose ethinyl-oestradiol, no gestodene or desogestrel) versus no use, 3.2 (2.3 to 4.3); for third generation products (low dose ethinyloestradiol, gestodene or desogestrel) versus no use, 4.8 (3.4 to 6.7); for third generation products versus second generation products, 1.5 (1.1 to 2.1); for products containing gestodene versus second generation products, 1.5 (1.0 to 2.2); and for products containing desogestrel versus second generation products, 1.5 (1.1 to 2.2). Probability of death due to venous thromboembolism for women using third generation products is about 20 per million users per year, for women using second generation products it is about 14 per million users per year, and for non-users it is five per million per year.
Risk of venous thromboembolism was slightly increased in users of third generation oral contraceptives compared with users of second generation products.
New studies about the influence of hormonal contraception on the risk of venous thromboembolism (VTE) have been published.
To evaluate new epidemiological data and to propose clinical consequences.
A literature survey.
Studies assessing the risk of specific types of hormonal contraception were evaluated, compared and set into a clinical perspective.
The majority of newer studies have demonstrated a threefold increased risk of VTE in current users of medium- and low-dose combined oral contraceptives (COCs) with norethisterone, levonorgestrel (LNG) or norgestimate compared with non-users. The same studies have demonstrated a sixfold increased risk of VTE in users of combined pills with desogestrel, gestodene, drospirenone or cyproteroneacetate, and in users of the contraceptive vaginal ring, compared with non-users. The rate ratio of VTE between users of COCs with newer progestogens compared with users of COCs with LNG was 1.5-2.8 in seven studies and 1.0 in two studies. Progestogen-only contraception did not confer an increased risk of VTE in any study. The incidence rate of VTE in non-pregnant women aged 15-49 years using non-hormonal contraception is three per 10 000 years.
For women starting on hormonal contraception, we recommend medium- or low-dose combined pills with norethisterone, LNG or norgestimate as first-choice preparations. For the many women who are users of COCs with newer progestogens, although the absolute risk of VTE is low, a change to combined pills with norethisterone, LNG or norgestimate may halve their risk of VTE. Finally, we recommend COCs with 20 μg estrogen combined with the older progestogens to be launched in the Scandinavian countries. Women at an increased risk of VTE should consider progestogen-only contraception or non-hormonal contraception.
The rate of unintended pregnancy in the United States is much higher than in other developed nations. Approximately half of unintended pregnancies are due to contraceptive failure, largely owing to inconsistent or incorrect use.
We designed a large prospective cohort study to promote the use of long-acting reversible contraceptive methods as a means of reducing unintended pregnancies in our region. Participants were provided with reversible contraception of their choice at no cost. We compared the rate of failure of long-acting reversible contraception (intrauterine devices [IUDs] and implants) with other commonly prescribed contraceptive methods (oral contraceptive pills, transdermal patch, contraceptive vaginal ring, and depot medroxyprogesterone acetate [DMPA] injection) in the overall cohort and in groups stratified according to age (less than 21 years of age vs. 21 years or older).
Among the 7486 participants included in this analysis, we identified 334 unintended pregnancies. The contraceptive failure rate among participants using pills, patch, or ring was 4.55 per 100 participant-years, as compared with 0.27 among participants using long-acting reversible contraception (hazard ratio after adjustment for age, educational level, and history with respect to unintended pregnancy, 21.8; 95% confidence interval, 13.7 to 34.9). Among participants who used pills, patch, or ring, those who were less than 21 years of age had a risk of unintended pregnancy that was almost twice as high as the risk among older participants. Rates of unintended pregnancy were similarly low among participants using DMPA injection and those using an IUD or implant, regardless of age.
The effectiveness of long-acting reversible contraception is superior to that of contraceptive pills, patch, or ring and is not altered in adolescents and young women. (Funded by the Susan Thompson Buffet Foundation.).
To assess the risk of venous thrombosis in current users of non-oral hormonal contraception.
Historical national registry based cohort study.
Four national registries in Denmark.
All Danish non-pregnant women aged 15-49 (n=1,626,158), free of previous thrombotic disease or cancer, were followed from 2001 to 2010.
Incidence rate of venous thrombosis in users of transdermal, vaginal, intrauterine, or subcutaneous hormonal contraception, relative risk of venous thrombosis compared with non-users, and rate ratios of venous thrombosis in current users of non-oral products compared with the standard reference oral contraceptive with levonorgestrel and 30-40 µg oestrogen. Diagnoses were confirmed by at least four weeks of anticoagulation therapy after the diagnosis.
Within 9,429,128 woman years of observation, 5287 first ever venous thrombosis events were recorded, of which 3434 were confirmed. In non-users of hormonal contraception the incidence rate of confirmed events was 2.1 per 10,000 woman years. Compared with non-users of hormonal contraception, and after adjustment for age, calendar year, and education, the relative risk of confirmed venous thrombosis in users of transdermal combined contraceptive patches was 7.9 (95% confidence interval 3.5 to 17.7) and of the vaginal ring was 6.5 (4.7 to 8.9). The corresponding incidences per 10,000 exposure years were 9.7 and 7.8 events. The relative risk was increased in women who used subcutaneous implants (1.4, 0.6 to 3.4) but not in those who used the levonorgestrel intrauterine system (0.6, 0.4 to 0.8). Compared with users of combined oral contraceptives containing levonorgestrel, the adjusted relative risk of venous thrombosis in users of transdermal patches was 2.3 (1.0 to 5.2) and of the vaginal ring was 1.9 (1.3 to 2.7).
Women who use transdermal patches or vaginal rings for contraception have a 7.9 and 6.5 times increased risk of confirmed venous thrombosis compared with non-users of hormonal contraception of the same age, corresponding to 9.7 and 7.8 events per 10,000 exposure years. The risk was slightly increased in women using subcutaneous implants but not in those using the levonorgestrel intrauterine system.
Oral spironolactone has been used for over two decades in the dermatological setting. Although it is not generally considered a primary option in the management of female patients with acne vulgaris, the increase in office visits by post-teenage women with acne vulgaris has recently placed a spotlight on the use of this agent in this subgroup of patients. This article reviews the literature focusing on the use of oral spironolactone in this subset of women with acne vulgaris, including discussions of the recommended starting dose, expected response time, adjustments in therapy, potential adverse effects, and patient monitoring.
Routine pelvic examinations are the core of the periodic gynecological examination and widely tolerated as a necessary part of health maintenance. Is this examination beneficial for asymptomatic women? Justifications for the pelvic examination include screening for Chlamydia (or gonorrhea) infection, evaluation before initiation of hormonal contraception, screening for cervical cancer, and early detection of ovarian cancer. Current nucleic acid amplification tests for Chlamydia and gonorrhea permit the use of urine and self-administered vaginal swabs, which most women prefer over a pelvic examination. Pelvic examination findings do not affect the decision to prescribe or withhold systemic hormonal contraception; a pelvic examination is not needed to initiate these contraceptives. Recent American College of Obstetricians and Gynecologists (ACOG) guidelines recommend less frequent cervical screening, thus decreasing the frequency of a speculum examination for cervical screening. Bimanual examinations for palpation of the uterus and ovaries are also routinely performed in the United States. Clinical trial data, however, show these examinations do not lead to earlier detection of ovarian cancer. No evidence identifies benefits of a pelvic examination in the early diagnosis of other conditions in the asymptomatic woman. Speculum and bimanual examinations are uncomfortable, disliked by many women, and use scarce time during a well woman visit. Eliminating the speculum examination from most visits and the bimanual examination from all visits of asymptomatic women will free resources to provide services of proven benefit. Overuse of the pelvic examination contributes to high healthcare costs without any compensatory health benefit.
Fear from increased cancer risk is one of the most significant reasons for low acceptance of reliable contraceptive methods and low compliance.
In this review, we included all cohort and case-control studies published in English up to December 2008. They were identified through a search of the literature using Pubmed and EMBASE.
Data about breast cancer risk indicate a slightly increased risk among current users of oral contraceptives (OC), an effect which disappears 5-10 years after stopping. Combined OC have a significant protective effect on the risk of ovarian cancer, and the protection increases with duration of use (relative risk decreased by 20% for each 5 years of use). The significant risk reduction has been confirmed for BRCA 1 and 2 mutation carriers. The risk of endometrial cancer is reduced by about 50% in ever users, a benefit which is greater with increasing duration of use. An association has been found between increased risk of cervical cancer and long-term OC use. Current OC use has been associated with an excess risk of benign liver tumours and a modest increased risk of liver cancer. None of large prospective cohort studies with prolonged follow-up has observed an increased overall risk of cancer incidence or mortality among ever users of OC, indeed several have suggested important long-term benefits. Specifically, protective effect of OC can be used as chemoprevention in young women who are BRCA mutation carriers.
Women wishing to use combined OC can be reassured that their decision is unlikely to place them at higher risk of developing cancer.
This report presents detailed pregnancy rates for 1990-2005, updating a national series of rates extending since 1976.
Tabular data on pregnancy rates by age, race and Hispanic origin, and by marital status are presented and briefly described.
in 2005, an estimated 6,408,000 pregnancies resulted in 4.14 million live births, 1.21 million induced abortions, and 1.06 million fetal losses. The 2005 pregnancy rate of 103.2 pregnancies per 1000 women aged 15-44 years is 11 percent below the 1990 peak of 115.8. The teenage pregnancy rate dropped 40 percent from 1990 to 2005, reaching an historic low of 70.6 per 1000 women aged 15-19 years. Rates fell much more for younger than for older teenagers.
The use of oral contraceptives is associated with an increased risk of venous thrombosis. It is now generally accepted that women who use oral contraceptives that contain so-called third-generation progestins (desogestrel or gestodene) are exposed to a twofold higher risk of venous thrombosis than women who use oral contraceptives that contain the second-generation progestin levonorgestrel. Coagulation studies demonstrated that oral contraceptives increase the plasma level of prothrombin, decrease the level of protein S and induce acquired activated protein C resistance. The changes in hemostatic parameters can explain why women who use oral contraceptives are exposed to an increased risk of venous thrombosis and why the risk is further increased in third-generation oral contraceptive users.
It is common in emergency departments (EDs) for emergency nurse practitioners (ENPs) or doctors to prescribe antibiotics for and dispense antibiotics to women who are also taking the oral contraceptive pill (OCP) and for more junior staff to dispense the prescriptions. Women who take OCPs are advised to take extra contraceptive precautions while taking and for seven days after finishing their antibiotics. Those who finish their current packs of OCPs before the end of this seven-day period are advised to start their next packet of OCPs without a break (Gibbons et al 2003). Women are given this advice because of the potential interaction of the two types of drug which can lead to OCP failure and therefore unplanned pregnancy. This article reviews the literature that describes these interactions and examines the basis of this advice. (excerpt)
Objective: To provide current and emerging evidence on oral contraceptives and the risk of venous thromboembolism. Evidence: Articles published in English from 2005 were retrieved through searches of PubMed and Medline, using the following terms: venous thromboembolism, VTE, contraception, oral contraceptives, hormonal contraception. Results were restricted to systematic reviews, randomized control trials/controlled clinical trials, and observational studies. Searches were updated on a regular basis and incorporated in the guideline to May 2010. Grey (unpublished) literature was identified through searching the websites of health technology assessment and health technology assessment-related agencies, clinical practice guideline collections, clinical trial registries, and national and international medical specialty societies. Values: The quality of evidence was rated using the criteria described by the Canadian Task Force on Preventive Health Care (Table). Summary Statements: 1.Modern oral contraceptives offer highly effective contraception and a range of non-contraceptive benefits. (I)2.Venous thromboembolism, although rare, remains one of the serious adverse consequences of hormonal contraception. Best evidence indicates that venous thromboembolism rates in non-users of reproductive age approximate 4-5/10 000 women per year; rates in oral contraceptive users are in the range of 9-10/10 000 women per year. For comparison, venous thromboembolism rates in pregnancy approach 29/10 000 overall and may reach 300-400/10 000 in the immediate postpartum period. (II-1)3.Research demonstrates that oral contraceptives with ≤ 35 μg of ethinyl estradiol carry a lower risk of venous thromboembolism than oral contraceptives with 50 μg. (II-2) Although preliminary data suggest a possible further reduction in venous thromboembolism with oral contraceptives with < 35 μg ethinyl estradiol, robust data to support this conclusion are presently lacking.4.Recent contradictory evidence and the ensuing media coverage of the venous thromboembolism risk attributed to the progestin component of certain newer oral contraceptive products have led to fear and confusion about the safety of oral contraceptives in general and drospirenone-containing oral contraceptives in particular. "Pill scares" of this nature have occurred in the past, with panic stopping of the pill, increased rates of unplanned pregnancy, and no subsequent decrease in venous thromboembolism rates. (II-3)5.Two high quality research studies that addressed the venous thromboembolism risk associated with various oral contraceptives found comparable venous thromboembolism rates with drospirenone-containing oral contraceptives and other approved products. (II-1)6.Two reports suggesting an increased risk of venous thromboembolism with drospirenone-containing oral contraceptives have significant methodological flaws that render their conclusions suspect. It seems likely that residual confounding could have distorted both the results and the conclusions of these reports. (II-3).
Background: The risk for venous thromboembolism during pregnancy or postpartum is uncertain. Objectives: To estimate the relative and absolute risk for deep venous thrombosis and pulmonary embolism during pregnancy and postpartum and to describe trends in incidence. Design: Population-based inception cohort study using the resources of the Rochester Epidemiology Project. Setting: Olmsted County, Minnesota. Patients: Women with deep venous thrombosis or pulmonary embolism first diagnosed between 1966 and 1995, including women with venous thromboembolism during pregnancy or the postpartum period (defined as delivery of a newborn no more than 3 months before the deep venous thrombosis or pulmonary embolism event date, including delivery of a stillborn infant after the first trimester). Measurements: The authors obtained yearly counts of live births in Olmsted County between 1966 and 1995 from the Minnesota Department of Health. Results: The relative risk (standardized incidence ratio) for venous thromboembolism among pregnant or postpartum women was 4.29 (95% Cl, 3.49 to 5.22; P< 0.001), and the overall incidence of venous thromboembolism (absolute risk) was 199.7 per 100 000 woman-years. The annual incidence was 5 times higher among postpartum women than pregnant women (511.2 vs. 95.8 per 100 000), and the incidence of deep venous thrombosis was 3 times higher than that of pulmonary embolism (151.8 vs. 47.9 per 100 000). Pulmonary embolism was relatively uncommon during pregnancy versus the postpartum period (10.6 vs. 159.7 per 100 000). Over the 30-year study period, the incidence of venous thromboembolism during pregnancy remained relatively constant whereas the postpartum incidence of pulmonary embolism decreased more than 2-fold. Limitations: Because the Olmsted County population was 98% white and of non-Hispanic ethnicity, the results may not be generalizable to other ethnicities. Conclusions: Among pregnant women, the highest risk period for venous thromboembolism and pulmonary embolism in particular is during the postpartum period. Any prophylaxis against these events should be particularly targeted to postpartum women. Although the incidence of pulmonary embolism has decreased over time, the incidence of deep venous thrombosis remains unchanged, indicating the need to better identify pregnant women at increased risk.
Drospirenone 3mg with ethinylestradiol 20µg (Yaz®) is a low-dose combined oral contraceptive (COC) administered in a regimen of 24 days of active tablets followed by a short hormone-free interval (4 days; 24/4 regimen). Drospirenone, unlike other synthetic progestogens used in COCs, is a 17α-spirolactone derivative and a 17α-spironolactone analogue with antimineralocorticoid and antiandrogenic properties. Drospirenone/ethinylestradiol 3mg/20µg (24/4) is approved in the US for the prevention of pregnancy in women, for the treatment of the symptoms of premenstrual dysphoric disorder (PMDD) and for the treatment of moderate acne vulgaris in women who wish to use an oral contraceptive for contraception.
Drospirenone/ethinylestradiol 3mg/20µg (24/4) provided 99% contraceptive protection over 1 year of treatment in two large studies. The same treatment regimen over three treatment cycles also significantly improved the emotional and physical symptoms associated with PMDD, and improved moderate acne vulgaris over six treatment cycles in double-blind trials. It was generally well tolerated, with adverse events generally typical of those experienced with other COCs and which were most likely to occur in the first few cycles. Clinical trials indicate that drospirenone/ethinylestradiol 3mg/20µg (24/4) is a good long-term contraceptive option, and additionally offers relief of symptoms that characterise PMDD and has a favourable effect on moderate acne vulgaris.
Pharmacological Properties
The pharmacological properties of ethinylestradiol are well established. Drospirenone is a 17α-spirolactone derivative and an analogue of 17α-spironolactone that resembles endogenous progesterone and has antimineralocorticoid and antian-drogenic properties. Drospirenone/ethinylestradiol 3mg/20µg administered as a 24/4 (Yaz®) or 21/7 regimen for two treatment cycles suppressed ovarian activity during daily recommended use; however, stronger suppression of ovarian activity was observed with the 24/4 regimen during intentional dosing errors (three active tablets replaced with placebo at the start of a third treatment cycle).
Like natural progesterone, drospirenone induces mild natriuresis, which counteracts estrogen-stimulated fluid retention and weight gain. The effects of drospirenone/ethinylestradiol 3mg/20µg on metabolic parameters, including lipoproteins, were generally neutral or favourable, although, as with other COCs, the serum glucose response to an oral glucose tolerance test in healthy women volunteers increased from baseline. As drospirenone is a spironolactone analogue with antimineralocorticoid activity, it has the potential to induce hyperkalaemia in high-risk patients (those with conditions that predispose them to hyperkalaemia [i.e. renal insufficiency, hepatic dysfunction and adrenal insufficiency] or those receiving other medications that may increase serum potassium).
Both drospirenone and ethinylestradiol are rapidly absorbed, with maximum serum concentration reached after 1.5 hours. Both are ≥97% plasma bound, with volumes of distribution of ≈4–5 L/kg. Steady-state levels of drospirenone are reached on day 8, and of ethinylestradiol in the second half of the cycle. Metabolism of both components, including first pass metabolism of ethinylestradiol, is extensive. The elimination half-life of drospirenone is ≈30 hours andthat of ethinylestradiol is ≈24 hours. Drospirenone exposure is slightly increased in women with renal impairment and markedly increased in those with hepatic dysfunction, with drospirenone/ethinylestradiol 3mg/20µg (24/4) contraindicated in both of these groups.
Therapeutic Efficacy
In two 1-year (13 contraceptive treatment cycles), noncomparative, international and EU trials enrolling 1027 and 1101 healthy women aged 17–36 years, oral drospirenone/ethinylestradiol 3mg/20µg (24/4) provided 99% contraceptive protection. The uncorrected Pearl index (PI) in the international trial was 1.29 and the PI adjusted for noncompliance was 0.72; in the EU trial, the uncorrected PI was 0.49. The cumulative pregnancy rates were 1.26% and 0.5% in the international and EU trials. Subjective satisfaction ratings (overall satisfaction, emotional and physical well-being, and interest in continuing medication if available) assessed in the international trial were positive in 73–88% of women.
The drospirenone/ethinylestradiol 3mg/20µg (24/4) regimen was shown to improve the emotional and physical symptoms associated with PMDD over three treatment cycles in two double-blind, parallel-group (n = 449) or crossover (n = 64) studies. In both trials, the improvement in overall luteal phase Daily Record of Severity of Problems (DRSP) scores (primary outcome) versus baseline was significantly greater in drospirenone/ethinylestradiol 3mg/20µg (24/4) than placebo recipients, while in the parallel-group trial, scores for physical, behavioural and mood subscales were also significantly improved. In both trials, the improvement from baseline in all individual DRSP items, including premenstrual depression, were significantly greater in drospirenone/ethinylestradiol 3mg/20µg (24/4) than in placebo recipients.
In the treatment of moderate acne vulgaris, drospirenone/ethinylestradiol 3mg/20µg (24/4) was generally well tolerated and was more effective than placebo in reducing the number of acne lesions and increasing the proportion of patients with ‘clear’ or ‘almost clear’ ratings on an Investigator Static Global Assessment scale in two large (n = 431 and 458) randomised, double-blind, placebo-controlled multicentre trials over six treatment cycles.
Tolerability
Once-daily drospirenone/ethinylestradiol 3mg/20µg in a 24/4 day regimen was generally well tolerated. Irregular bleeding (actively solicited), headache, nausea and breast pain were the most common adverse events; all tended to decrease over time in the 1-year, international trial. There were no clinically significant changes in potassium levels or other laboratory investigations and no abnormalities in adequate-sample endometrial biopsies after 13 cycles.
Adverse events were generally similar in the double-blind, 3-month studies in PMDD, although irregular bleeding (spontaneously reported) was more common in the parallel-group trial. The proportion of drospirenone/ethinylestradiol 3mg/20µg (24/4) recipients who discontinued treatment for this reason was <4% in the parallel-group PMDD study and <1% in the international contraceptive trial. Other common adverse events were headache, nausea and breast pain in 13–20% of patients.
BACKGROUND This paper explores recent developments in female contraception, using them to illustrate how adaptation of existing methods,
improved service delivery and understanding contraceptive behaviour might increase contraceptive uptake and correct and consistent
use, and how the development of new methods holds some promise for capitalizing on the potential non-contraceptive benefits.
There is substantial evidence that use of an intrauterine device (IUD) reduces the risk of endometrial cancer. Little is known about the potential effects of an IUD on the risk of developing cervical cancer or cervical human papillomavirus (HPV) infection. A number of studies have addressed the concern that these devices could cause cervical cancer, but the results have been inconclusive. This study used pooled data from 2 large epidemiologic studies that explored the potential effects of IUD use on the risk of cervical HPV infection and the risk of developing cervical cancer. The 2 studies were conducted by the International Agency for Research on Cancer and Institut Català d'Oncologia research program on HPV and cervical cancer. Data from 1 study were obtained from 10 case–control studies of cervical cancer conducted in 8 countries; the other study included data for 16 HPV prevalence surveys from 14 countries for women in the general population. The final pooled analysis included 2205 women with cervical cancer and 2214 matched control women without cervical cancer from the case–control studies, and 15,272 healthy women from the HPV surveys. Personal interviews with participants provided information on potential risk factors for cervical cancer, including IUD use and duration of polymerase chain reaction-based assays, which were used to detect HPV DNA. Multivariate unconditional logistic regression analysis was used to estimate the associations between IUD use and both cervical HPV DNA and cervical cancer, and to adjust the latter for covariates, including cervical HPV DNA and number of previous Papanicolaou smears. The adjusted data show a strong and consistent inverse association between ever use of an IUD and cervical cancer. The adjusted odds ratio (aOR) was 0.55, with a 95% confidence interval (CI) of 0.42 to 0.70 (P < 0.0001). A protective association was found between IUD use and the cervical cancer histologic subtypes, squamous cell carcinoma (aOR, 0.56; 95% CI, 0.43–0.72; P < 0.0001) and combined adenocarcinoma and adenosquamous carcinomas (aOR, 0.46; 0.22–0.97; P = 0.035) but not for HPV-positive women (aOR, 0.68; 95% CI, 0.44–1.06; P = 0.11). None of the surveys showed an association between IUD use and cervical HPV-DNA detection among women without cervical cancer. These findings show that use of IUDs substantially reduces the risk of cervical cancer. Although the underlying mechanisms in reducing the risk of developing cervical cancer are unclear, the data suggest that IUD use could act as a protective cofactor in cervical carcinogenesis and/or may trigger cellular immunity.
Dermatologists prescribe oral antibiotics to female acne patients on a regular basis. There have been reports of oral antibiotic interaction with oral contraceptive preparations,1-3 but no clinical study has precisely defined the risk for women taking these medications in combination with oral antibiotics. Amid the uncertainty, some dermatologists recommend that their female acne patients use additional birth control measures as a precaution. Our study examines the frequency of pregnancy in female acne patients taking oral antibiotics in conjunction with oral contraceptives compared with published failure rates for women taking birth control pills alone.
Materials and Methods.
Female acne patients were interviewed by mail questionnaire and by survey in an outpatient dermatology clinic. Patients were questioned about concurrent usage of their antibiotic and oral contraceptive preparations. Pregnancy occurrence and side effects were also investigated. Further inquiries were made concerning the use of additional medications while receiving the pill/antibiotic combination and
The assumption that the metabolism of testosterone to 5α-dihydrotestosterone (5α-DHT) is required for androgen action in the skin was investigated by studying the uptake and metabolism of testosterone by skin and other tissues of the rat in vivo. The skin resembled the classical androgen target organs in the uptake and retention of radioactivity, but the proportions of the steroids present were markedly different. In the ventral prostate most of the testosterone was metabolized, mainly to 5α-DHT, after only 20 min. In the skin testosterone was always the predominant steroid identified and androstenedione, 5α-DHT, 5α-androstane-3α, 17β-diol, androsterone and 5α-androstane-3β, 17β-diol were only present in much smaller quantities, even after 5 h. Hypophysectomy, known to reduce the response of the sebaceous glands to testosterone in the rat, did not alter the steroid composition in the classical target organs, the preputial glands, or the plasma, but in the skin it increased testosterone metabolism without altering the levels of 5α-DHT or the 5α-androstane-diols. These results suggest that the 5α-reduction of testosterone to 5α-DHT may not be so important in the skin, or at least in the sebaceous glands, as it is in the prostate.
Objective:
To investigate the efficacy, safety, removal characteristics, and x-ray visibility of Nexplanon, a radiopaque etonogestrel contraceptive implant combined with a next-generation applicator.
Study design:
A 3-year, nocomparative, multicenter study in women aged 18-40 years at 23 clinical sites.
Results:
Of 301 women who had an implant inserted, none became pregnant while the implant was in situ. Serious adverse events were reported in 16 of 301 (5.3%) women; none were judged as drug related. Fibrosis around the implant was the most common removal complication (4.4%). The implant was visible on X-ray and palpable before removal with a mean removal time of 2 minutes.
Conclusion:
Nexplanon showed high contraceptive efficacy, palpability before removal, short removal times, and few removal complications. Nexplanon provides clinicians with a long-term hormonal contraceptive method with a safety and efficacy profile comparable to Implanon, radiopacity, and a new applicator.
Teen pregnancy continues to plague the United States. This review will discuss long-acting reversible contraceptive (LARC) method use in teens, comprising intrauterine devices and subdermal implants.
The American College of Obstetricians and Gynecologists along with the American Academy of Pediatrics, the Centers for Disease Control, and the World Health Organization have recognized the potential impact of LARC (comprising intrauterine contraception and subdermal implants) to reduce unintended pregnancies. They have affirmed the safety of such devices, and no effects on long-term fertility have been identified. Teen users of these methods have been shown to have high continuation and satisfaction rates. On the contrary, oral contraceptive pills, the patch, and the contraceptive vaginal ring have significantly higher contraceptive failure rates, and these rates are magnified in young women.
LARC methods should be considered first-line options for teens seeking contraception.
To inform about the risk of venous thromboembolism (VTE) of different hormonal contraceptives in different patient groups.
Combined oral contraceptives (COCs) differ significantly regarding VTE risk depending on amount of estrogen and type of progestogen: COCs containing desogestrol, gestoden or drospirenone in combination with ethinylestradiol (so called third-generation or fourth-generation COCs) are associated with a higher VTE risk than COCs with ethinylestradiol and levonorgestrel or norethisterone (so called second-generation COCs). The VTE risk for transdermal COCs like vaginal ring (NuvaRing) or patch (Evra) is as high as for COCs of third or fourth generation. Progestogen-only contraceptive methods do not increase VTE risk significantly. New kinds of COC without ethinylestradiol but with estradiol valerat or estradiol showed a much lower degree of coagulation activation than 'classical' COC containing ethinylestradiol.
Second-generation COCs should be the first choice when prescribing hormonal contraception.In patients with a history of VTE and/or a known thrombophilic defect, COCs are contraindicated, but progestogen-only contraceptives can be safely used in this patient group. Whether newer COCs with estradiol valerate or estradiol have a lower VTE risk remains to be elucidated.
We have established a sensitive and specific radioreceptor assay for androgen receptor active materials in plasma, using tritiated methyltrienolone ([3H]R 1881) as tracer, and spayed mouse kidney cytosol receptor as the binding species. On radioreceptor assay, plasma from mice chronically administered spironolactone contained ˜ 10 times higher levels of androgen receptor active material than from mice administered potassium canrenoate. In parallel bioassays (antagonism of the effect of testosterone on seminal vesicle weight), spironolactone was >4 times as potent an antiandrogen as potassium canrenoate. Administered potassium canrenoate circulates as canrenoic acid, in equilibrium with its lactonized congener canrenone. Since over 80% of administered spironolactone is irreversibly converted to canrenone/canrenoic acid, its much higher anti-androgen activity on radioreceptor assay and bioassay may point to the generation of unidentified, minor metabolites with very high affinity for androgen receptors and/or a very long plasma half-life.
Priority health-risk behaviors, which are behaviors that contribute to the leading causes of morbidity and mortality among youth and adults, often are established during childhood and adolescence, extend into adulthood, and are interrelated and preventable.
September 2010-December 2011.
The Youth Risk Behavior Surveillance System (YRBSS) monitors six categories of priority health-risk behaviors among youth and young adults: 1) behaviors that contribute to unintentional injuries and violence; 2) tobacco use; 3) alcohol and other drug use; 4) sexual behaviors that contribute to unintended pregnancy and sexually transmitted diseases (STDs), including human immunodeficiency virus (HIV) infection; 5) unhealthy dietary behaviors; and 6) physical inactivity. In addition, YRBSS monitors the prevalence of obesity and asthma. YRBSS includes a national school-based Youth Risk Behavior Survey (YRBS) conducted by CDC and state and large urban school district school-based YRBSs conducted by state and local education and health agencies. This report summarizes results from the 2011 national survey, 43 state surveys, and 21 large urban school district surveys conducted among students in grades 9-12.
Results from the 2011 national YRBS indicated that many high school students are engaged in priority health-risk behaviors associated with the leading causes of death among persons aged 10-24 years in the United States. During the 30 days before the survey, 32.8% of high school students nationwide had texted or e-mailed while driving, 38.7% had drunk alcohol, and 23.1% had used marijuana. During the 12 months before the survey, 32.8% of students had been in a physical fight, 20.1% had ever been bullied on school property, and 7.8% had attempted suicide. Many high school students nationwide are engaged in sexual risk behaviors associated with unintended pregnancies and STDs, including HIV infection. Nearly half (47.4%) of students had ever had sexual intercourse, 33.7% had had sexual intercourse during the 3 months before the survey (i.e., currently sexually active), and 15.3% had had sexual intercourse with four or more people during their life. Among currently sexually active students, 60.2% had used a condom during their last sexual intercourse. Results from the 2011 national YRBS also indicate many high school students are engaged in behaviors associated with the leading causes of death among adults aged ≥ 25 years in the United States. During the 30 days before the survey, 18.1% of high school students had smoked cigarettes and 7.7% had used smokeless tobacco. During the 7 days before the survey, 4.8% of high school students had not eaten fruit or drunk 100% fruit juices and 5.7% had not eaten vegetables. Nearly one-third (31.1%) had played video or computer games for 3 or more hours on an average school day.
Since 1991, the prevalence of many priority health-risk behaviors among high school students nationwide has decreased. However, many high school students continue to engage in behaviors that place them at risk for the leading causes of morbidity and mortality. Variations were observed in many health-risk behaviors by sex, race/ethnicity, and grade. The prevalence of some health-risk behaviors varied substantially among states and large urban school districts.
YRBS data are used to measure progress toward achieving 20 national health objectives for Healthy People 2020 and one of the 26 leading health indicators; to assess trends in priority health-risk behaviors among high school students; and to evaluate the impact of broad school and community interventions at the national, state, and local levels. More effective school health programs and other policy and programmatic interventions are needed to reduce risk and improve health outcomes among youth.
Current evidence suggests that post-adolescent acne in women is on the rise. Acne in this subgroup of patients commonly follows a specific pattern that can often be treatment resistant and/or prone to relapse, including after oral isotretinoin therapy. With a plethora of medications to choose from for acne treatment, many of which have been used in the past by patients without success, dermatology practitioners often find oral contraceptives and spironolactone to be of benefit in otherwise healthy adult females. Also, some of these patients may have concurrent hormonal anomalies such as polycystic ovarian syndrome or other underlying endocrine disorders, which should also be appropriately worked up by the clinician and managed accordingly. This article reviews some of the underlying pathophysiological factors, available treatment options, and screening guidelines to assist clinicians in the management of acne in adult females.
In affluent societies, median age at menarche has dropped to below 13 years. Younger age at menarche is associated with earlier sexual activity. To avoid unintended teenage pregnancies, barriers to contraception provision must be kept low, i.e. availability without prescription or through a low-threshold prescription system, low-cost options and long-term prescriptions or easy refills. Since many adolescents are (over)concerned about side effects, these should be addressed. A gynaecological examination prior to prescription is no longer recommended. All effective reversible contraceptive methods are available to adolescents: user-based hormonal contraceptives, trimonthly depot medroxyprogesterone acetate (DMPA), and long-acting reversible contraception (LARC). User-based hormonal contraceptives carry a small absolute risk of venous thromboembolism (~4 per 10,000 patient-years), but the risk is more than tenfold higher among young women with an inherited clotting defect. DMPA reduces bone mineral accumulation, but this is a reversible effect; the metabolic risks, including weight gain and insulin resistance, appear to be greater. LARC, including intrauterine contraceptive devices and the progestogen-containing implant, is gaining popularity among teenagers; abnormal bleeding is the main side effect. Any effective contraceptive should preferably be combined with consistent condom use to prevent sexually transmitted infections ("the double Dutch").
Adolescent women have a high risk of unintended pregnancy. Currently, there are little data about their choice to initiate long-acting reversible contraception (LARC).
We evaluated the association of age and preference for a LARC vs. a non-LARC method among adolescent participants in the Contraceptive CHOICE Project, comparing those aged 14-17 years to adolescents aged 18-20 years. We then analyzed the association between age and choice of the implant vs. the intrauterine device (IUD) among adolescents.
Of the 5086 women enrolled, 70% (n=3557) of participants chose a LARC method. Among adolescents aged 14-20 years, 69% of 14-17-year-olds chose LARC, while 61% of 18-20-year-olds chose LARC (relative risk 1.16, 95% confidence interval 1.03-1.30). Among adolescents choosing a LARC method, 63% (n=93/148) of the 14-17-year-olds chose the implant, whereas 71% (n=364/510) of the 18-20-year-olds chose the IUD.
Long-acting reversible contraception use is clearly acceptable and common among adolescents enrolled in the Contraceptive CHOICE Project, with the younger group being most interested in the implant.
Intrauterine device (IUD) use has been shown to reduce the risk of endometrial cancer, but little is known about its association with cervical cancer risk. We assessed whether IUD use affects cervical human papillomavirus (HPV) infection and the risk of developing cervical cancer.
We did a pooled analysis of individual data from two large studies by the International Agency for Research on Cancer and Institut Català d'Oncologia research programme on HPV and cervical cancer; one study included data from ten case-control studies of cervical cancer done in eight countries, and the other included data from 16 HPV prevalence surveys of women from the general population in 14 countries. 2205 women with cervical cancer and 2214 matched control women without cervical cancer were included from the case-control studies, and 15,272 healthy women from the HPV surveys. Information on IUD use was obtained by personal interview. HPV DNA was tested by PCR-based assays. Odds ratios and 95% CIs were estimated using multivariate unconditional logistic regression for the associations between IUD use, cervical HPV DNA, and cervical cancer.
After adjusting for relevant covariates, including cervical HPV DNA and number of previous Papanicolaou smears, a strong inverse association was found between ever use of IUDs and cervical cancer (odds ratio 0·55, 95% CI 0·42-0·70; p<0·0001). A protective association was noted for squamous-cell carcinoma (0·56, 0·43-0·72; p<0·0001), adenocarcinoma and adenosquamous carcinoma (0·46, 0·22-0·97; p=0·035), but not among HPV-positive women (0·68, 0·44-1·06; p=0·11). No association was found between IUD use and detection of cervical HPV DNA among women without cervical cancer.
Our data suggest that IUD use might act as a protective cofactor in cervical carcinogenesis. Cellular immunity triggered by the device might be one of several mechanisms that could explain our findings.
Instituto de Salud Carlos III; Agència de Gestió d'Ajuts Universitaris i Recerca; Marató TV3 Foundation; Bill & Melinda Gates Foundation; International Agency for Research on Cancer; European Community; Fondo de Investigaciones Sanitarias, Spain; Preventiefonds, Netherlands; Programa Interministerial de Investigación y Desarrollo, Spain; Conselho Nacional de Desenvolvimiento Cientifico e Tecnologico, Brazil; and Department of Reproductive Health & Research, WHO.
In Germany today, one-third of the 20 million women of child-bearing age use combined oral contraceptives (COCs). In this article, we summarize the current knowledge of the mode of action, wanted and unwanted side effects, and long-term risks of COCs. The levonorgestrel intrauterine device (IUD) and long-acting injectable or implantable monophasic progestogen preparations offer comparable contraceptive efficacy to COCs. Nonetheless, they are less frequently used in Germany than COCs, because of their propensity to cause breakthrough bleeding.
Selective review of the literature.
COCs suppress gonadotropin secretion and thereby inhibit follicular maturation and ovulation. Their correct use is associated with 0.3 pregnancies per 100 women per year, their typical use, with 1 pregnancy per 100 women per year (Pearl index). COCs have effects on the cardiovascular and hemostatic systems as well as on lipid and carbohydrate metabolism. When given in the presence of specific risk factors, they significantly increase the likelihood of cardiovascular disease and thromboembolism. Women with persistent human papilloma virus (HPV) infection who take COCs are at increased risk of developing invasive cervical cancer. On the other hand, COCs lower the cumulative incidence of endometrial and ovarian cancer by 30% to 50%, and that of colorectal cancer by 20% to 30%. Other malignancies seem to be unaffected by COC use.
As long as personal and familial risk factors are carefully considered, COCs constitute a safe, reversible, and well-tolerated method of contraception.
To review the association between combined oral contraceptives and cardiovascular disease, with emphasis on oral contraceptives containing low doses of estrogen (low-dose oral contraceptives).
A systematic search of the MEDLINE database was done for all relevant articles published between 1967 (when low-dose oral contraceptives were introduced in the United States) and June 1997. Textbooks, meeting proceedings, and reference lists were also searched.
All English-language human epidemiology studies of oral contraceptives that used cardiovascular disease as an end point were reviewed. Animal and metabolic studies were reviewed only if they were especially relevant to the mechanism of action of oral contraceptives.
Descriptive and analytic data from each study were collected.
Data were organized by cardiovascular end point, study design, estrogen dose, and type of progestogen. Data on relative and absolute risk are presented to address current prescription guidelines.
The risk for cardiovascular disease is lower with current preparations of oral contraceptives, including those that contain the new progestogens, than with older oral contraceptives containing high doses of estrogen. Among users of low-dose oral contraceptives, cardiovascular diseases occur mainly in smokers and women with predisposing factors. Every effort should be made to encourage smoking cessation among potential users of oral contraceptives.
To estimate 12-month satisfaction and continuation rates of intrauterine device (IUD) and implant users enrolled in the Contraceptive CHOICE Project and compare these measures with women using the oral contraceptive pills (OCPs).
We analyzed 12-month data from the first 5,087 participants enrolled in a prospective cohort study of women in the St. Louis region offered contraception at no cost for 3 years. The primary purpose of CHOICE is to promote the use of long-acting reversible contraception (IUDs and implants) and to reduce unintended pregnancies in our region. This analysis includes those participants who received their baseline contraceptive method within 3 months of enrollment and who reached the 12-month follow-up telephone survey time point (n=4,167).
Sixty-eight percent of our participants chose a long-acting reversible contraception method (45% levonorgestrel intrauterine system, 10% copper IUD, and 13% subdermal implant), 23% chose combined hormonal methods (11% OCPs, 10% vaginal ring, and 2% transdermal patch), and 8% chose depot medroxyprogesterone acetate. Long-acting reversible contraception users had higher 12-month continuation rates (86%) than OCP users (55%). The two IUDs had the highest 12-month continuation rates: levonorgestrel intrauterine system (88%) and copper IUD (84%). Women using the implant also had very high rates of continuation at 1 year (83%). Satisfaction mirrored continuation: more than 80% of users were satisfied with the IUD compared with 54% satisfied with OCPs.
IUDs and the subdermal implant have the highest rates of satisfaction and 12-month continuation. Given that long-acting reversible contraception methods have the highest contraceptive efficacy, these methods should be the first-line contraceptive methods offered to patients.
This review provides an update of previous estimates of first-year probabilities of contraceptive failure for all methods of contraception available in the United States. Estimates are provided of probabilities of failure during typical use (which includes both incorrect and inconsistent use) and during perfect use (correct and consistent use). The difference between these two probabilities reveals the consequences of imperfect use; it depends both on how unforgiving of imperfect use a method is and on how hard it is to use that method perfectly. These revisions reflect new research on contraceptive failure both during perfect use and during typical use.
Objective:
To provide current and emerging evidence on oral contraceptives and the risk of venous thromboembolism.
Evidence:
Articles published in English from 2005 were retrieved through searches of PubMed and Medline, using the following terms: venous thromboembolism, VTE, contraception, oral contraceptives, hormonal contraception. Results were restricted to systematic reviews, randomized control trials/controlled clinical trials, and observational studies. Searches were updated on a regular basis and incorporated in the guideline to May 2010. Grey (unpublished) literature was identified through searching the websites of health technology assessment and health technology assessment-related agencies, clinical practice guideline collections, clinical trial registries, and national and international medical specialty societies.
Values:
The quality of evidence was rated using the criteria described by the Canadian Task Force on Preventive Health Care (Table). SUMMARY STATEMENTS: 1. Modern oral contraceptives offer highly effective contraception and a range of non-contraceptive benefits. (I) 2. Venous thromboembolism, although rare, remains one of the serious adverse consequences of hormonal contraception. Best evidence indicates that venous thromboembolism rates in non-users of reproductive age approximate 4-5/10 000 women per year; rates in oral contraceptive users are in the range of 9-10/10 000 women per year. For comparison, venous thromboembolism rates in pregnancy approach 29/10 000 overall and may reach 300-400/10 000 in the immediate postpartum period. (II-1) 3. Research demonstrates that oral contraceptives with ≤ 35 µg of ethinyl estradiol carry a lower risk of venous thromboembolism than oral contraceptives with 50 µg. (II-2) Although preliminary data suggest a possible further reduction in venous thromboembolism with oral contraceptives with < 35 µg ethinyl estradiol, robust data to support this conclusion are presently lacking. 4. Recent contradictory evidence and the ensuing media coverage of the venous thromboembolism risk attributed to the progestin component of certain newer oral contraceptive products have led to fear and confusion about the safety of oral contraceptives in general and drospirenone-containing oral contraceptives in particular. "Pill scares" of this nature have occurred in the past, with panic stopping of the pill, increased rates of unplanned pregnancy, and no subsequent decrease in venous thromboembolism rates. (II-3) 5. Two high quality research studies that addressed the venous thromboembolism risk associated with various oral contraceptives found comparable venous thromboembolism rates with drospirenone-containing oral contraceptives and other approved products. (II-1) 6. Two reports suggesting an increased risk of venous thromboembolism with drospirenone-containing oral contraceptives have significant methodological flaws that render their conclusions suspect. It seems likely that residual confounding could have distorted both the results and the conclusions of these reports. (II-3).
CDC created U.S. Medical Eligibility Criteria for Contraceptive Use, 2010, from guidance developed by the World Health Organization (WHO) and finalized the recommendations after consultation with a group of health professionals who met in Atlanta, Georgia, during February 2009. This guidance comprises recommendations for the use of specific contraceptive methods by women and men who have certain characteristics or medical conditions. The majority of the U.S. guidance does not differ from the WHO guidance and covers >60 characteristics or medical conditions. However, some WHO recommendations were modified for use in the United States, including recommendations about contraceptive use for women with venous thromboembolism, valvular heart disease, ovarian cancer, and uterine fibroids and for postpartum and breastfeeding women. Recommendations were added to the U.S. guidance for women with rheumatoid arthritis, history of bariatric surgery, peripartum cardiomyopathy, endometrial hyperplasia, inflammatory bowel disease, and solid organ transplantation. The recommendations in this document are intended to assist health-care providers when they counsel women, men, and couples about contraceptive method choice. Although these recommendations are meant to serve as a source of clinical guidance, health-care providers should always consider the individual clinical circumstances of each person seeking family planning services.
Background:
The delivery of combination contraceptive steroids from a transdermal contraceptive patch or a contraceptive vaginal ring offers potential advantages over the traditional oral route. The transdermal patch and vaginal ring could require a lower dose due to increased bioavailability and improved user compliance.
Objectives:
To compare the contraceptive effectiveness, cycle control, compliance (adherence), and safety of the contraceptive patch or the vaginal ring versus combination oral contraceptives (COCs).
Search methods:
Through February 2013, we searched MEDLINE, POPLINE, CENTRAL, LILACS, ClinicalTrials.gov, and ICTRP for trials of the contraceptive patch or the vaginal ring. Earlier searches also included EMBASE. For the initial review, we contacted known researchers and manufacturers to identify other trials.
Selection criteria:
We considered randomized controlled trials comparing a transdermal contraceptive patch or a contraceptive vaginal ring with a COC.
Data collection and analysis:
Data were abstracted by two authors and entered into RevMan. For dichotomous variables, the Peto odds ratio (OR) with 95% confidence intervals (CI) was calculated. For continuous variables, the mean difference was computed. We also assessed the quality of evidence for this review.
Main results:
We found 18 trials that met our inclusion criteria. Of six patch studies, five examined the marketed patch containing norelgestromin plus ethinyl estradiol (EE); one studied a patch in development that contains levonorgestrel (LNG) plus EE. Of 12 vaginal ring trials, 11 examined the same marketing ring containing etonogestrel plus EE; one studied a ring being developed that contains nesterone plus EE.Contraceptive effectiveness was not significantly different for the patch or ring versus the comparison COC. Compliance data were limited. Patch users showed better compliance than COC users in three trials. For the norelgestromin plus EE patch, ORs were 2.05 (95% CI 1.83 to 2.29) and 2.76 (95% CI 2.35 to 3.24). In the levonorgestrel plus EE patch report, patch users were less likely to have missed days of therapy (OR 0.36; 95% CI 0.25 to 0.51). Of four vaginal ring trials, one found ring users had more noncompliance (OR 3.99; 95% CI 1.87 to 8.52), while another showed more compliance with the regimen (OR 1.67; 95% CI 1.04 to 2.68).More patch users discontinued early than COC users. ORs from two meta-analyses were 1.59 (95% CI 1.26 to 2.00) and 1.56 (95% CI 1.18 to 2.06) and another trial showed OR 2.57 (95% CI 0.99 to 6.64). Patch users also had more discontinuation due to adverse events than COC users. Users of the norelgestromin-containing patch reported more breast discomfort, dysmenorrhea, nausea, and vomiting. In the levonorgestrel-containing patch trial, patch users reported less vomiting, headaches, and fatigue.Of 11 ring trials with discontinuation data, two showed the ring group discontinued less than the COC group: OR 0.32 (95% CI 0.16 to 0.66) and OR 0.52 (95% CI 0.31 to 0.88). Ring users were less likely to discontinue due to adverse events in one study (OR 0.32; 95% CI 0.15 to 0.70). Compared to the COC users, ring users had more vaginitis and leukorrhea but less vaginal dryness. Ring users also reported less nausea, acne, irritability, depression, and emotional lability than COC users.For cycle control, only one trial study showed a significant difference. Women in the patch group were less likely to have breakthrough bleeding and spotting. Seven ring studies had bleeding data; four trials showed the ring group generally had better cycle control than the COC group.
Authors' conclusions:
Effectiveness was not significantly different for the methods compared. Pregnancy data were available from half of the patch trials but two-thirds of ring trials. The patch could lead to more discontinuation than the COC. The patch group had better compliance than the COC group. Compliance data came from half of the patch studies and one-third of the ring trials. Patch users had more side effects than the COC group. Ring users generally had fewer adverse events than COC users but more vaginal irritation and discharge.The quality of the evidence for this review was considered low for the patch and moderate for the ring. The main reasons for downgrading were lack of information on the randomization sequence generation or allocation concealment, the outcome assessment methods, high losses to follow up, and exclusions after randomization.
Standard systemic therapeutic agents used in acne include oral antimicrobials, isotretinoin, and hormonal agents. Appropriate patient selection is the key to decide when to use hormonal agents as first-line therapy as well as to achieve optimal results. Indications of hormonal therapy in acne in girls and women include proven ovarian or adrenal hyperandrogenism, recalcitrant acne, acne not responding to repeated courses of oral isotretinoin, acne tarda, polycystic ovary syndrome, or the presence of clinical signs of hyperandrogenism such as androgenic alopecia or the presence of the seborrhea, acne, hirsutism, alopecia syndrome. We describe the hormonal agents currently available for acne treatment, discuss their indications and contraindications, and address the question of whether they may be used as a first-line therapy in acne.
Concern has been raised that the risk of venous thromboembolism (VTE) in users of the ORTHO EVRA patch is higher compared to users of oral contraceptives (OCs).
We identified idiopathic cases of VTE and controls, matched on age and index date, from among women in the United States PharMetrics/IMS and MarketScan databases who were current users of the patch or levonorgestrel-containing OCs with 30 mcg of ethinyl estradiol. We calculated odds ratios (ORs) and 95% confidence intervals (CIs).
The ORs (95% CI) for VTE in users of the patch compared to levonorgestrel-containing OCs were 2.0 (0.9-4.1) and 1.3 (0.8-2.1) in the PharMetrics and MarketScan databases, respectively. ORs (95% CI) restricted to women aged 39 years or younger were 1.4 (0.6-3.0) and 1.2 (0.7-2.0), respectively.
These results provide evidence that the risk of idiopathic VTE in users of the patch is not materially different than that of users of levonorgestrel-containing OCs in women aged 39 years or younger. We cannot rule out some increase in the risk in women aged 40 years or older.
ABSTRACT One of the primary factors contributing to the development of acne vulgaris is excess sebum. Sebaceous glands and sebum excretion are regulated, at least in part, by androgen hormones. Acne treatments that block this androgen effect include spironolactone and combination oral contraceptives (COC). Three COC are now FDA approved to treat moderate acne. Dermatologists must become experts at prescribing these hormonal contraceptives. Likewise, it is vital to be aware of contraindications to hormonal contraceptive therapy. Proper patient selection relies on an appropriate medical history and an assessment of blood pressure. A pelvic exam and/or Papanicolaou smear are not required prior to initiating therapy with a COC. It is important to counsel patients about potential adverse effects of COC pills and to establish appropriate expectations concerning acne improvement.
Background:
Fear of pain during insertion of intrauterine contraception (IUC) is a barrier to use of this method. IUC includes copper-containing intrauterine devices and levonorgestrel-releasing intrauterine systems. Interventions for pain control during IUC insertion include non-steroidal anti-inflammatory drugs (NSAIDs), local cervical anesthetics, and cervical ripening agents such as misoprostol.
Objectives:
To review randomized controlled trials (RCTs) of interventions for reducing IUC insertion-related pain
Search methods:
We searched for trials in CENTRAL, MEDLINE, EMBASE, POPLINE, ClinicalTrials.gov, and ICTRP. The most recent search was 22 June 2015. We examined reference lists of pertinent articles. For the initial review, we wrote to investigators to find other published or unpublished trials.
Selection criteria:
We included RCTs that evaluated an intervention for preventing IUC insertion-related pain. The comparison could have been a placebo, no intervention, or another active intervention. The primary outcomes were self-reported pain at tenaculum placement, during IUC insertion, and after IUC insertion (up to six hours).
Data collection and analysis:
Two authors extracted data from eligible trials. For dichotomous variables, we calculated the Mantel-Haenszel odds ratio (OR) with 95% confidence interval (CI). For continuous variables, we computed the mean difference (MD) with 95% CI. In meta-analysis of trials with different measurement scales, we used the standardized mean difference (SMD).
Main results:
We included 33 trials with 5710 participants total; 29 were published from 2010 to 2015. Studies examined lidocaine, misoprostol, NSAIDs, and other interventions. Here we synthesize results from trials with sufficient outcome data and moderate- or high-quality evidence.For lidocaine, meta-analysis showed topical 2% gel had no effect on pain at tenaculum placement (two trials) or on pain during IUC insertion (three trials). Other formulations were effective compared with placebo in individual trials. Mean score for IUC-insertion pain was lower with lidocaine and prilocaine cream (MD -1.96, 95% CI -3.00 to -0.92). Among nulliparous women, topical 4% formulation showed lower scores for IUC-insertion pain assessed within 10 minutes (MD -15.90, 95% CI -22.77 to -9.03) and at 30 minutes later (MD -11.10, 95% CI -19.05 to -3.15). Among parous women, IUC-insertion pain was lower with 10% spray (median 1.00 versus 3.00). Compared with no intervention, pain at tenaculum placement was lower with 1% paracervical block (median 12 versus 28).For misoprostol, meta-analysis showed a higher mean score for IUC insertion compared with placebo (SMD 0.27, 95% CI 0.07 to 0.46; four studies). In meta-analysis, cramping was more likely with misoprostol (OR 2.64, 95% CI 1.46 to 4.76; four studies). A trial with nulliparous women found a higher score for IUC-insertion pain with misoprostol (median 46 versus 34). Pain before leaving the clinic was higher for misoprostol in two trials with nulliparous women (MD 7.60, 95% CI 6.48 to 8.72; medians 35.5 versus 20.5). In one trial with nulliparous women, moderate or severe pain at IUC insertion was less likely with misoprostol (OR 0.30, 95% CI 0.16 to 0.55). In the same trial, the misoprostol group was more likely to rate the experience favorably. Within two trials of misoprostol plus diclofenac, shivering, headache, or abdominal pain were more likely with misoprostol. Participants had no vaginal delivery. One trial showed the misoprostol group less likely to choose or recommend the treatment.Among multiparous women, mean score for IUC-insertion pain was lower for tramadol 50 mg versus naproxen 550 mg (MD -0.63, 95% CI -0.94 to -0.32) and for naproxen versus placebo (MD -1.94, 95% CI -2.35 to -1.53). The naproxen group was less likely than the placebo group to report the insertion experience as unpleasant and not want the medication in the future. An older trial showed repeated doses of naproxen 300 mg led to lower pain scores at one hour (MD -1.04, 95% CI -1.67 to -0.41) and two hours (MD -0.98, 95% CI -1.64 to -0.32) after insertion. Most women were nulliparous and also had lidocaine paracervical block.
Authors' conclusions:
Nearly all trials used modern IUC. Most effectiveness evidence was of moderate quality, having come from single trials. Lidocaine 2% gel, misoprostol, and most NSAIDs did not help reduce pain. Some lidocaine formulations, tramadol, and naproxen had some effect on reducing IUC insertion-related pain in specific groups. The ineffective interventions do not need further research.
Interest in sebaceous gland physiology and its diseases is rapidly increasing. We provide a summarized update of the current knowledge of the pathobiology of acne vulgaris and new treatment concepts that have emerged in the last 3 years (2005-2008). We have tried to answer questions arising from the exploration of sebaceous gland biology, hormonal factors, hyperkeratinization, role of bacteria, sebum, nutrition, cytokines and toll-like receptors (TLRs). Sebaceous glands play an important role as active participants in the innate immunity of the skin. They produce neuropeptides, excrete antimicrobial peptides and exhibit characteristics of stem cells. Androgens affect sebocytes and infundibular keratinocytes in a complex manner influencing cellular differentiation, proliferation, lipogenesis and comedogenesis. Retention hyperkeratosis in closed comedones and inflammatory papules is attributable to a disorder of terminal keratinocyte differentiation. Propionibacterium acnes, by acting on TLR-2, may stimulate the secretion of cytokines, such as interleukin (IL)-6 and IL-8 by follicular keratinocytes and IL-8 and -12 in macrophages, giving rise to inflammation. Certain P. acnes species may induce an immunological reaction by stimulating the production of sebocyte and keratinocyte antimicrobial peptides, which play an important role in the innate immunity of the follicle. Qualitative changes of sebum lipids induce alteration of keratinocyte differentiation and induce IL-1 secretion, contributing to the development of follicular hyperkeratosis. High glycemic load food and milk may induce increased tissue levels of 5alpha-dihydrotestosterone. These new aspects of acne pathogenesis lead to the considerations of possible customized therapeutic regimens. Current research is expected to lead to innovative treatments in the near future.
Background:
Hirsutism is the presence of excessive hair growth in women and is an important cosmetic condition often resulting in severe distress. The most common cause is by increased production of male sex hormones (androgens). It is also affected by increased sensitivity to androgens in the hair follicles, and secretory glands around hair follicles (sebaceous glands). Spironolactone is an antiandrogen and aldosterone antagonist used to treat hirsutism.
Objectives:
The objective was to investigate the effectiveness of spironolactone and/or in combination with steroids (oral contraceptive pill included) in reducing excess hair growth and/or acne in women.
Search strategy:
The Cochrane Menstrual Disorders and Subfertility Group (MDSG) trials register was searched (April 2008). The Cochrane MDSG register is based on regular searches of MEDLINE, EMBASE, CINAHL, PsycINFO and CENTRAL, handsearching of 20 relevant journals and conference proceedings, and searches of several key grey literature sources. In addition, all reference lists of relevant trials were searched and drug companies contacted for details of unpublished trials.
Selection criteria:
All randomised controlled comparisons of spironolactone versus: placebo, steroids (oral contraceptive pill included), spironolactone of varying dosages, or spironolactone and steroids versus steroids alone when used to reduce hair growth and acne in women.
Data collection and analysis:
Nine trials were included in the review, eight trials were excluded. Two other trials are awaiting assessment. Only one trial studied acne as an outcome, the remainder were concerned with hirsutism. Major outcome measures include the following: subjective observations, Ferriman and Gallwey hair scores, hormonal and biochemical parameters, side effects, sebum production measurement.
Main results:
In the two trials that compared 100 mg of spironolactone with placebo significant differences were reported for subjective improvements in hair growth (OR 7.18, 95% CI 1.96 to 26.28), although not the Ferriman-Galwey score (WMD 7.20, 95% CI -10.98 to -3.42)). Data could not be otherwise pooled as only one trial reported an outcome.
Authors' conclusions:
From the studies included in this review, there is some evidence to show that spironolactone is an effective treatment to decrease the degree of hirsutism but there was no evidence for effectiveness for the treatment of acne vulgaris. Studies in this area are scarce and small. Individual study data indicates some superiority of spironolactone over other drugs but results cannot be generalised.
The study was conducted to estimate the relative cost effectiveness of contraceptives in the United States from a payer's perspective.
A Markov model was constructed to simulate costs for 16 contraceptive methods and no method over a 5-year period. Failure rates, adverse event rates and resource utilization were derived from the literature. Sensitivity analyses were performed on costs and failure rates.
Any contraceptive method is superior to "no method". The three least expensive methods were the copper-T intrauterine device (IUD) (US$647), vasectomy (US$713) and levonorgestrel (LNG)-20 intrauterine system (IUS) (US$930). Results were sensitive to the cost of contraceptive methods, the cost of an unintended pregnancy and plan disenrollment rates.
The copper-T IUD, vasectomy and the LNG-20 IUS are the most cost-effective contraceptive methods available in the United States. Differences in method costs, the cost of an unintended pregnancy and time horizon are influential factors that determine the overall value of a contraceptive method.
To assess the efficacy of the combined oral contraceptive containing 3-mg drospirenone/20-microgram ethinyl estradiol (3-mg drospirenone/20-microgram ethinyl estradiol) administered as 24 consecutive days of active treatment after a 4-day hormone-free interval (24/4 regimen) compared with placebo for the treatment of moderate acne vulgaris.
Healthy females aged 14-45 years with moderate acne were randomized in this double-blind study to 3-mg drospirenone/20-microgram ethinyl estradiol (n=270) or placebo (n=268) for six cycles of 28 days. The primary outcome measures of acne lesion counts and Investigator Static Global Assessment scale ratings were assessed at baseline and during cycles 1, 3, and 6.
The percentage reduction from baseline to endpoint for total lesions is 46.3% for 3-mg drospirenone/20-microgram ethinyl estradiol 24/4 combination oral contraceptive group and 30.6% for placebo group (P<.001). The likelihood of participants in the 3-mg drospirenone/20-microgram ethinyl estradiol 24/4 regimen group having "clear" or "almost clear" skin as rated by the investigators at endpoint was about threefold (odds ratio 3.13, 95% confidence interval 1.69-5.81; P=.001) greater than in the placebo group. The 3-mg drospirenone/20-microgram ethinyl estradiol 24/4 regimen was well tolerated.
The low-dose combined oral contraceptive containing 3-mg drospirenone/20-microgram ethinyl estradiol administered in a 24/4 regimen significantly reduced acne lesion counts more effectively than placebo and demonstrated greater improvement in the Investigator Static Global Assessment rating of acne. The safety profile was consistent with low-dose combined oral contraceptive use.
Acne affects more than 40 million people, of which more than half are women older than 25 years of age. These women frequently fail traditional therapy and have high relapse rates even after isotretinoin. Recent advances in research have helped to delineate the important role hormones play in the pathogenesis of acne. Androgens such as dihydrotestosterone and testosterone, the adrenal precursor dehydroepiandrosterone sulfate, estrogens, growth hormone, and insulin-like growth factors may all contribute to the development of acne. Hormonal therapy remains an important part of the arsenal of acne treatments available to the clinician. Women dealing with acne, even those without increased serum androgens, may benefit from hormonal treatments. The mainstays of hormonal therapy include oral contraceptives and antiandrogens such as spironolactone, cyproterone acetate, or flutamide. In this article, we discuss the effects of hormones on the pathogenesis of acne, evaluation of women with suspected endocrine abnormalities, and the myriad of treatment options available.