Síndrome dos ovários policísticos: tratamento das manifestações androgênicas / Polycystic ovary syndrome: treatment of androgenic manifestations

A síndrome dos ovários policísticos (SOP) é um distúrbio endócrino-metabólico muito frequente no período reprodutivo. Quando associado ao distúrbio metabólico, as mulheres com SOP podem ter ainda risco acrescido para doença cardiovascular. O objetivo deste manuscrito é descrever as repercussões metabólicas, incluindo quais as principais, como investigar e as consequências desse distúrbio sobre a saúde da mulher. É uma revisão narrativa mostrando a implicação da resistência insulínica, das dislipidemias e da síndrome metabólica sobre o sistema reprodutor e sobre o risco cardiovascular da mulher com SOP, bem como do uso de sensibilizadores de insulina no seu tratamento. Conclui-se que a correção dos distúrbios metabólicos na SOP é benéfica tanto para o sistema reprodutor quanto para o cardiovascular. A primeira linha de tratamento é a mudança de estilo de vida e a perda de peso. Na resposta inadequada, o tratamento medicamentoso está recomendado. Nas mulheres com obesidade mórbida que não tiveram bons resultados com o tratamento clínico, a cirurgia bariátrica é uma opção.(AU)

Hormone therapy in acne.

Underlying hormone imbalances may render acne unresponsive to conventional therapy. Relevant investigations followed by initiation of hormonal therapy in combination with regular anti-acne therapy may be necessary if signs of hyperandrogenism are present. In addition to other factors, androgen-stimulated sebum production plays an important role in the pathophysiology of acne in women. Sebum production is also regulated by other hormones, including estrogens, growth hormone, insulin, insulin-like growth factor-1, glucocorticoids, adrenocorticotropic hormone, and melanocortins. Hormonal therapy may also be beneficial in female acne patients with normal serum androgen levels. An understanding of the sebaceous gland and the hormonal influences in the pathogenesis of acne would be essential for optimizing hormonal therapy. Sebocytes form the sebaceous gland. Human sebocytes express a multitude of receptors, including receptors for peptide hormones, neurotransmitters and the receptors for steroid and thyroid hormones. Various hormones and mediators acting through the sebocyte receptors play a role in the orchestration of pathogenetic lesions of acne. Thus, the goal of hormonal treatment is a reduction in sebum production. This review shall focus on hormonal influences in the elicitation of acne via the sebocyte receptors, pathways of cutaneous androgen metabolism, various clinical scenarios and syndromes associated with acne, and the available therapeutic armamentarium of hormones and drugs having hormone-like actions in the treatment of acne.

Efecto de un anticonceptivo oral con drospirenona/etinilestradiol (3 mg - 30 mg) sobre el hiperandrogenismo clínico y bioquímico en pacientes con síndrome de ovario poliquístico / Effect of an oral contraceptive containing drospirenone / ethinyl estradiol (3 mg - 30 mg) on the clinical and biochemical hyperandrogenism in patients with polycystic ovary syndrome

El síndrome de ovario poliquístico es un desorden heterogéneo de etiología incierta, que cual afecta entre el 6% y 10% de las mujeres en edad reproductiva. Una de las opciones terapéuticas especificas es el uso de los anticonceptivos orales, con la progestina, drospirerona, la cual, es un análogo de la espironolactona que posee actividad antimineralcorticoides y antiandrogénica. El objetivo de este estudio fue determinar el efecto del anticonceptivo oral combinado (EE: 30 MG y DRP: 3 mg) en el perfil bioquímico y clínico en una población de mujeres venezolanas con síndrome de ovario poliquístico. De las 20 pacientes incluidas en el estudio, 18 completaron satisfactoriamente el estudio, con una buena tolerancia al tratamiento. Se observó una disminución del IMC de 23,94 en condición basal a 23,73 kg/m². Los niveles de andrógenos se encontraron disminuidos significativamente en comparación a la basal; testosterona total cayó de 1,4 ng/mL a 0,67 ng/mL; Testosterona libre bajo de 3 pg/mL a 1,38 pg/mL; DHEAS disminuyó de 1,65 µg/mL a 1,08 µg/mL y androstenediona de 2,50 ng/mL a 1,55 ng/mL. En conclusión nuestros resultados reportan que el uso de un anticonceptivo oral que contiene 30 mg de EE y 3 mg de progestina, drospirerona en una población de mujeres venezolanas con síndrome de ovario poliquístico condujo a una disminución de los niveles de andrógenos al mismo tiempo que se evidenció un incremento de la SHBG, así como una reducción no significativa del peso corporal de este grupo de pacientes y una mejoría clínica del hirsutismo.

Policystic ovarian syndrome is a heterogeneous disorder wich etiology remained uncertain and affects 6%-10% of reproductive age women. Most recommended therapy is oral contraceptives with progestins. Drospirenone is an espironolactone analogue exhibits a partial antiandrogenic action and has predominant anti-mineralocorticoid properties. This is a prospective trial to determine efficacy of a drospirenone-containing combined oral contraceptives in venezuelan women with polycystic ovary-syndrome. Twenty women were conducted into this trial, although 18 were treated. With treatment, BMI fell by 0,21 kg/m(2) in the study group. During therapy, the levels of testosterone, free testosterone, Delta (4)-androstenedione, and androstenedione decreased significantly, whereas sex hormone-binding globulin increased significantly. Treatment of women with polycystic ovary-syndrome with drospironene containing combined oral contraceptives formulations is effective in decreasing hirsutism, androgen levels and BMI.

Tratamento hormonal da acne baseado em evidências / Hormonal treatment of acne based on evidence

Este trabalho de revisão apresenta o tratamento hormonal da acne baseado em evidências. O trabalho resume a clínica, a classificação, a fisiopatologia e a etiologia da acne. A avaliação de estudos selecionados mostrou que o tratamento hormonal da acne deve ser complementado por tratamento cosmiátrico, e não está indicado para gestantes ou mulheres com planos de engravidar. A primeira escolha para esse tratamento são os contraceptivos hormonais orais, pois são efetivos e seguros para tratamento da acne e também para anticoncepção. Após tempo estabelecido, se o resultado for insatisfatório, outro medicamento, como acetato de ciproterona ou espironolactona, deve ser adicionado. A finasterida é o medicamento indicado para acne de origem idiopática, e a flutamida apresenta efeitos colaterais significativos, não constituindo indicação segura até o momento.

This review shows the hormonal treatment of acne. The review summarizes the clinical aspects, classification, physiopathology and etiology of the acne. The evaluation of selected papers showed that hormonal treatment of acne with hormones has to be complemented by esthetics treatment and is not prescribed for pregnant women or those who want to get pregnant. The first choice of treatment is the hormonal oral contraceptive one, because it is effective and safe for treatment of acne and also for contraception. After an established period with unsatisfactory results, other medicines, such as ciproterone acetate or spironolactone, can be added. The finasteride is prescribed for idiopathic acne and flutamide has many relevant side effects and is also not safe.

[Indication of metformin in the management of hormonal dysfunction secondary to polycystic ovarian syndrome: prospective comparative study about 63 cases]

Polycystic ovarian syndrome [PCOS] is the most common hormonal dysfunction in women. It's a cause of female infertility by oligoanovulation, clinical and biochemical hyperandrogenism and polycystic ovaries. Weight loss, firstly proposed in overweight or obese patient suffering from PCOS, aims to reduce hyperinsulinism and hyperandrogenism. Recently, Metformin, an insulin sensitizer, has been proposed as an alternative first line treatment for polycystic ovarian syndrome by improving hyperinsulinemia and hyperandrogenism in these women. The aim of our study, and through a literature review, is to demonstrate if Metformin should be used as a first-line drug for infertile women with this syndrome or as an adjunction to Clomifene Citrate, the longest established treatment already used in this syndrome. A prospective comparative study including 63 patients with PCOS has been done during 2 years. Women were randomly allocated to clomifene + Metformin [Metformin group, Metformin took during 8 weeks, 850 mg twice a day, plus Clomifene 100 mg per day during five days] or Clomifene only [100 mg per day during five days]. All patients underwent a two- month's diet. The middle age was about 30.63 years and the body mass index [BMI] was about 29.88 kg/ m[2]. We noticed a 6.2% weight loss in both groups [a non significant difference in p=0.04]. The median of infertility period was about 2.49 years. The ovulation rate in the Metformin group was 53.12% [significant difference for inducing ovulation p=0.02] and 32.25% in Clomifene group [non-significant difference 0.07]. There was also a significant difference for ongoing pregnancies [p=0.04]. In fact, 11 on 32 patients [34%] achieved a full-term pregnancy in Metformin group versus only 4 ones on 31 patients [12.9%] in Clomifene group. Our conclusion is that Metformin is an effective addition to Clomifene Citrate in term of reestablishment of ovulation and full-term pregnancies achievement, excluding ART cycles

Low-dose glucocorticoids in hyperandrogenism / Efecto de bajas dosis de glucocorticoides en el hiperandrogenismo

To investigate the effect of low-doses of glucocorticoids on androgen and cortisol secretion during the course of the day, we evaluated clinical signs of hyperandrogenism and total, free and bioavailable testosterone, SHBG, and cortisol following two different protocols: A) fourteen patients received betamethasone 0.6 mg/day (n=8) or methylprednisolone 4 mg/day (n=6), as single daily oral dose at 11.00 PM, during 30 days, B) fourteen patients were evaluated under betamethasone 0.3 mg in a single daily dose at 11.00 PM during six months, 11 out of whom were re-evaluated six months later. Twenty eight women with hyperandrogenism were included and seven normal females were used as control. Blood samples were taken in follicular phase at 8 AM and 7 PM to determine SHBG, cortisol, total, free and bioavailable testosterone. In both protocols, a significant morning and evening decrease in cortisol and testosterone (p<0.05 to < 0.01), which was moremarked with betamethasone (p<0.05), was shown. In protocol B, morning SHBG levels showed a significant increase (p<0.05) and betamethasone also improved clinical hyperandrogenism along the trial. Although morning and evening cortisol significantly decreased during treatment, no side effects were reported. The 11 patients reevaluated after therapy withdrawal, showed a rise in serum total testosterone and its fractions to pre-treatment values and a normalization of cortisol levels. It is concluded that glucocorticoids in low-doses effectively normalize serum androgens, independently of their origin. They may be used therapeutically, mainly whenever a hyperandrogenic woman presents with cycle irregularities or seeking fertility.

Con el objetivo de investigar el efecto de bajas dosis de glucocorticoides sobre la secreción de andrógenos y cortisol en el curso del día, evaluamos signos de hiperandrogenismo, testosterona total, libre y biodisponible y cortisol según dos protocolos diferentes: A) catorce pacientes recibieron betametasona 0.6 mg/día (n= 8) o metilprednisolona 4 mg/día (n= 6) en dosis única cotidiana, a las 23 h, durante 30 días, B) catorce pacientes fueron evaluadas bajo betametasona 0.3 mg en dosis única cotidiana a la 23 h, administrada durante 6 meses; de ellas, 11 pacientes fueron re-evaluadas 6 meses más tarde. Se incluyeron 28 mujeres con hiperandrogenismo y 7 controles normales. Se obtuvieron muestras de sangre en fase folicular a las 08:00 y 9:00 h para determinar SHBG, cortisol, testosterona total, libre y biodisponible. En ambos protocolos se observó una disminución significativa de cortisol y testosterona (p<0.05 a <0.01), más importante con betametasona (p<0.05). En el protocolo B, los niveles matutinos de SHBG aumentaron significativamente (p<0.05) y se observó mejoría clínica con el tratamiento. Aunque los niveles matutinos y vespertinos de cortisol disminuyeron significativamente durante el tratamiento, no se observaron efectos secundarios. En las 11 pacientes reevaluadas luego de suspensión de glucocorticoides se observó un aumento de testosterona y sus fracciones a los niveles pre-tratamiento con normalización de las concentraciones de cortisol. Dosis bajas de glucocorticoides normalizaron eficazmente los andrógenos séricos elevados, independientemente de su causa. Pueden emplearse terapéuticamente, en especial cuando una mujer hiperandrogénica presenta alteraciones del ciclo menstrual o busca fertilidad.

Actualización de la terapia del hirsutismo / Update in the treatment of hirsutism

El hirsutismo es un síntoma del hiperandrogenismo femenino a nivel dermatológico y constituye en sí mismo un problema estético y psicosocial para la mujer. Se analizan las drogas involucradas en el tratamiento, el mecanismo de acción y efectos colaterales. La eficiencia y seguridad de ciproterona, espironolactona y flutamida en 3 grupos de mujeres hirsutas se comparan con los datos de la literatura.

Pregnancy rate following Metformin consumption in patients with PCOS under ART treatment

Infertility with an incidence of about 15% has mainly been one of the community burdens that have even been threatening to the continuity of the family life. One of the most prevalent causes of women infertility is ovarian causes particularly PCOS. Since Metformin may improve quality and increase the number of ova, and likewise increase fertilization rate via reducing the level of insulin, this study was conducted with aim of investigating responses of patients with PCOS in the cycle of ART. This was a randomized clinical trial on 100 infertile patients with PCOS who referred to Shariati Hospital in Tehran during 1999-2000. The subjects were randomly categorized in to 2 groups [A=44 and B=46 women]. Ten patients were eliminated from study due to ignoring the treatment plan. Group A received Metformin at a dose of 500 mg t.i.d in addition to induction of ovulation with long protocol. The results were analyzed using t-test and X2 and P<0.05 was considered as significant. Results showed that average level of estradiol in group A was 2159_1056pg/ml and 2842 +/- 1050 pg/ml in group B, with a significant difference [P=0.002]. We administered 23 +/- 7.6 ampules of HMG for the subject's in group A and 31.34 +/- 8.12 ampules for those in group B [P = 0.001]. The difference in number of oocytes was not significant, where as we found a significant difference in the number of germinal vesicle [P = 0.047]. There were no significant differences in course of treatment, numbers of oocytes and the number of pregnancy between 2 groups. Considering the findings of this study by using Metformin, we improve the quality of ova in patients with PCOS. This happens due to the effect of Metformin through reducing insulin resistance and hyperandrogenism in patients with PCOS leading to a prominent drop in estradiol levels in serum that in turn lowers the need for administration of HMG and result in improving oocyte quality

Tratamiento del hirsutismo con espironolactona y con espironolactona más dexametasona / Treatment of hirsutism with spironolactone and with spironolactone plus dexamethasone

Background: Spironolactone has an anti androgenic effect, inhibiting the binding of androgens to their receptor. This antagonistic effect is the basis for the use of spironolactone in the treatment of hirsutism. Aim: To study the effectiveness and safety of spironolactone in the treatment of hirsute women and of the association of spironolactone plus dexamethasone in the treatment of hirsutism with glucocorticoid sensitive hyperandrogenism. Patients and method: Sixteen women (group 1) with peripheral hirsutism (defined as those with normal androgens levels, normal menstrual cycles and ovulation) and 24 women (group 2) with glucocorticoid sensitive hyperandrogenic hirsutism were studied. Group 1 was treated with spironolactone 50 mg bid and group 2 with same spironolactone dose plus dexamethasone 0.5 mg at 23 h during one month and 0.25 mg thereafter. Patients were followed during one year. Results: After one year of treatment, a 54 percent reduction in Moncada hirsutism escore was observed in group 1 and 52 percent reduction in group 2. Observed secondary effects of spironolactone were increases in diuresis, fatigability, acne aggravation and seborrhea in two patients. Two additional patients had spotting. No secondary effect attributable to glucocorticoid use were observed. Conclusions: Spironolactone is effective and safe in the treatment of hirsutism. Androgenic supression did no increases its effectiveness, underscoring the peripheral anti androgenic activity os spironolactone

Evaluación del efecto agudo de la administración de GnRH sobre la secreción de leptina en mujeres sanas e hiperandrogénicas / Assessment of acute effect of GnRH administration on leptin secretion in normal and hyperandrogenic women

Background: Several studies suggest that leptin modulates the reproductive axis function. Leptin may stimulate release of GnRH from hypothalamus and of gonadotrophins from the pituitary. A synchronicity of LH and leptin pulses has been described in healthy women and in patients with polycystic ovarian syndrome (PCOS), suggesting a relationship between the episodic secretion of LH and leptin. In vitro experimental studies have demonstrated that leptin administration promotes GnRH-LH release. However it is not established whether GnRH promotes the episodic secretion of leptin. Aim: To assess the response of LH and leptin to the administration of a GnRH bolus in hyperandrogenic and healthy women. Patients and methods: Eleven hyperandrogenic and eleven healthy women of similar age and body mass index (BMI) were studied. Under basal conditions three blood samples were collected every 30 min before and after the administration of a GnRH bolus (100 µg). LH and leptin concentrations were measured in all samples. Testosterone, SHBG and estradiol were determined in the first sample. For data analysis, the increment of LH and leptin between 0-30 and 0-60 min. was calculated. The LH and leptin areas under the curve (AUC) before and after GnRH administration were also calculated in both groups. Results: After GnRH administration. an increment in LH concentrations was observed in both groups; however, leptin concentrations were not modified. In both groups LH area under the curve increased after GnRH administration; however, the leptin area was not modified. Conclusions: These results suggest that circulating leptin concentration is not modulated by GnRH-LH

El exceso de vello corporal en mujeres / Excess of body hair in women

El aumento de vello es un motivo frecuente de preocupación y de consulta femenina. Se definen los términos de hipertricosis, hirsutismo y virilismo, destacando que el hirsutismo es la aparción de vellosexual en zonas en las que su presencia es normal en el hombre pero no en la mujer. Se señalan los principales efectos cosméticos y funcionales del hiperandrogenismo en la mujer: hirsutismo, acné, seborrea, amenorrea, anovulación, atrofia mamaria, cliteromegalia, hiperplasia endometrial, obesidad, etc.Se enumeran las causas del hirsutismo, señalando que fisiol+ogicamente derivan de un aumento en la producción de andrógenos o de la sensibilidad frente a ellos de los folículos pilosos

Avaliaçäo clínica e laboratorial de 104 pacientes com hiperandrogenismo / Clinical and laboratorial evaluation of 104 patients with hyperandrogenism

Analisamos, neste trabalho, 104 pacientes com hiperandrogenismo do Ambulatório de Endocrinologia Tocoginecológica do HC-FMRP-USP, no período de 1980 a 1994. A idade média das pacientes foi de 25,5 + 6,0 anos, o hirsutismo a queixa clínica mais frequente; a SOMP, hirsutismo idiopático e a HACIT foram os principais diagnósticos. Diversas drogas foram utilizadas no controle da sintomatologia, tais como glicocorticóides, ACO, acetato de ciproterona, espironolactona, mas a média de abandono ao seguimento clínico foi elevada. Pudemos concluir que o hiperandrogenismo é uma entidade multifatorial que afeta mulheres jovens, e é de difícil manejo terapêutica já que o tratamento deve ser seguido a longo prazo ou mesmo ininterruptamente, o que leva grande parte das pacientes a abandonarem os serviços médicos.

Remisión prolongada del hiperandrogenismo femenino después de suspender la terapia con glucocorticoides / Prolonged remission of female hyperandrogenism after discontinuing glucocorticoid therapy

Adrenal androgen hypersecretion either produced by genetic defects or reticular disfunction, is reduced by exogenous glucocorticoid administration and as with any suppression therapy, it should relapse when the therapy is discontinued. However, prolonged remissions of adrenal androgen hypersecretion after discontinuing glucocorticoids have been described. We report 15 patients with adrenal hyperandrogenism and elevated levels of dehydroepiandrosterone sulfate that received treatment with dexamethasone. After 1 month of treatment with dexamethasone 0.5 mg/day, dehydroepiandrosterone sulfate levels returned to normal and remained so during a mean of 19 months receiving dexamethasone 0.25 mg/day. One year after discontinuing therapy, hormone levels continued within normal range in all patients. It is concluded that a long remission period of adrenal hyperandrogenism was achieves after discontinuing glucocorticoid therapy