Immunofluorescence Analysis of Estrogen and Progesterone Receptors and Ki-67 Nuclear Protein in Canine Uteri Treated with Medroxyprogesterone Acetate During Anestrus / Análisis de Inmunofluorescencia de Receptores de Estrógeno y Progesterona y Proteína Nuclear Ki-67 en Úteros Caninos Tratados con Acetato de Medroxiprogesterona Durante el Anestr

SUMMARY: Estradiol and progesterone receptors play an essential role in the changes occurring in the uterus during the estrus cycle in dogs (Canis lupus familiaris). In order to investigate the potential effect of progestational agent medroxyprogesterone acetate (MPA) when is used during anestrus on the expression of estradiol receptors [ER], progesterone receptors [PR] and nuclear protein Ki67, we evaluated uterine tissue immunohistochemically. Uteri were grouped as nulliparous (control, n=11), multiparous (n=11) and treated with MPA (n=11; nulliparous with two treatments; 5mg/kg; i.m.). The amount and location of PR, ER and Ki67 were studied on the epithelial surface, apical and basal regions of the endometrium and myometrium using immunohistochemical techniques with a spectral confocal microscope and analyzed by ANOVA. Differences in ER were observed between the multiparous and MPA-treated groups in the apical region of the endometrium (p=0.0022). Differences in cell proliferation were detected between the nulliparous and multiparous groups (p=0.0037) and nulliparous and MPA-treated groups (p=0.0003) in the basal region of the endometrium. In conclusion, two doses of MPA (5mg/kg; i.m.) do not have a significant effect on the expression of ER and PR; however, they inhibit cell proliferation in the basal region of the endometrium, which includes the stroma, subepithelial cell layer, compact layer, and spongy layer. The clinical and long-term effect of this treatment should be evaluated in subsequent studies.

Los receptores de estradiol y progesterona juegan un rol fundamental en los cambios que se producen en el útero durante el ciclo estral de las perras (Canis lupus familiaris). El objetivo de este estudio fue evaluar las expresiones de ER-a y PR en el útero y la proliferación de células endometriales detectando la expresión nuclear de la proteína Ki67 en perras expuestas a la progestina sintética MPA y compararlas con perras nulíparas y multíparas expuestas a progesterona luteal. Úteros fueron agrupados como nulíparas (control, n=11), multíparas (n=11) y tratadas con MPA (n=11; nulíparas con dos tratamientos; 5 mg/kg; i.m.). La expresión de PR, ER-a y Ki67 fue evaluada en la regiones apicales y basales del endometrio y miometrio con un microscopio confocal espectral. Se observó diferencias en ER-a entre los grupos multíparas y tratados con MPA en la región apical del endometrio (p=0,0022). Se detectaron diferencias en la proliferación celular entre los grupos de nulíparas y multíparas (p=0,0037) y los grupos de nulíparas y tratados con MPA (p=0,0003) en la región basal del endometrio. En conclusión, dos dosis de MPA (5mg/kg; i.m.) no tienen un efecto significativo sobre la expresión de ER y PR; sin embargo, inhiben la proliferación celular en la región basal del endometrio, el cual incluye a estroma, capa de células subepiteliales, estratos compacto y esponjoso. El efecto clínico a largo plazo de este tratamiento debe ser evaluado en estudios posteriores.

The efficacy of oral Micronized Progesterone versus Medroxyprogesterone Acetate in the control of mild to moderate abnormal uterine bleeding - ovulatory Dysfunction (AUB-O) in adolescents: An open label randomized controlled trial

Objectives@#To determine the efficacy of micronized oral progesterone (OMP) versus Medroxyprogesterone Acetate (MPA) in the control and regulation of mild to moderate abnormal uterine bleeding in adolescents with ovulatory dysfunction.@*Materials and Methods@#This is an open labelled Randomized Controlled Trial. Fifty patients with mild to moderate abnormal uterine bleeding were randomized to treatment with Medroxyprogesterone Acetate or Oral Micronized Progesterone.

Comparison of the effects and safety of dydrogesterone and medroxyprogesterone acetate on endometrial hyperplasia without atypia: a randomized controlled non-inferior phase Ⅲ clinical study / 中华妇产科杂志

Objective: To compare the effects and safety of dydrogesterone (DG) and medroxyprogesterone acetate (MPA) on the treatment in patients with endometrial hyperplasia without atypia (EH). Methods: This was a single-center, open-label, prospective non-inferior randomized controlled phase Ⅲ trial. From February 2019 to November 2021, patients with EH admitted to the Obstetrics and Gynecology Hospital of Fudan University were recruited. Enrolled patients were stratified according to the pathological types of simple hyperplasia (SH) or complex hyperplasia (CH), and were randomised to receive MPA or DG. Untill May 14, 2022, the median follow-up time after complete response (CR) was 9.3 months (1.1-17.2 months). The primary endpoint was the 6-month CR rate (6m-CR rate). The secondary endpoints included the 3-month CR rate (3m-CR rate), adverse events rate, recurrence rate, and pregnancy rate in one year after CR. Results: (1) A total of 292 patients with EH were enrolled in the study with the median age of 39 years (31-45 years). A total of 135 SH patients were randomly assigned to MPA group (n=67) and DG group (n=68), and 157 CH patients were randomly assigned to MPA group (n=79) and DG group (n=78). (2) Among 292 patients, 205 patients enrolled into the primary endpoint analysis, including 92 SH patients and 113 CH patients, with 100 patients in MPA group and 105 in DG group, respectively. The 6m-CR rate of MPA group and DG group were 90.0% (90/100) and 88.6% (93/105) respectively, and there were no statistical significance (χ2=0.11, P=0.741), with the rate difference (RD) was -1.4% (95%CI:-9.9%-7.0%). Stratified by the pathology types, the 6m-CR rate of SH patients was 93.5% (86/92), and MPA group and DG group were respectively 91.1% (41/45) and 95.7% (45/47); and the 6m-CR rate of CH patients was 85.8% (97/113), and MPA group and DG group were 89.1% (49/55) and 82.8% (48/58) respectively. The 6m-CR rates of the two treatments had no statistical significance either (all P>0.05). A total of 194 EH patients enrolled into the secondary endpoint analysis, including 88 SH patients and 106 CH patients, and 96 patients in MPA group and 98 in DG group, respectively. The 3m-CR rate of SH patients were 87.5% (77/88), while the 3m-CR rates of MPA group and DG group were 90.7% (39/43) and 84.4% (38/45), respectively; the 3m-CR rate of CH patients was 66.0% (70/106), and MPA group and DG group had the same 3m-CR rate of 66.0% (35/53). No statistical significance was found between the two treatments both in SH and CH patients (all P>0.05). (3) The incidence of adverse events between MPA group and DG group had no statistical significance (P>0.05). (4) A total of 93 SH patients achieved CR, and the cumulative recurrence rate in one year after CR were 5.9% and 0 in MPA group and DG group, respectively. While 112 CH patients achieved CR, and the cumulative recurrence rate in one year after CR were 8.8% and 6.5% in MPA group and DG group, respectively. There were no statistical significance between two treatment groups (all P>0.05). Among the 93 SH patients, 10 patients had family planning but no pregnancy happened during the follow-up period. Among the 112 CH patients, 21 were actively preparing for pregnancy, and the pregnancy rate and live-birth rate in one year after CR in MPA group were 7/9 and 2/7, while in DG group were respectively 4/12 and 2/4, and there were no statistical significance in pregnancy rate and live-birth rate between the two treatment groups (all P>0.05). Conclusions: Compared with MPA, DG is of good efficacy and safety in treating EH. DG is a favorable alternative treatment for EH patients.

Tratamiento hormonal de la pedofilia: ¿puede curar la pedofilia con la castración química? / Pedophilia hormonal therapy: can pedophilia be cured with chemical castration

Históricamente la sociedad ha rechazado el abuso sexual de menores de 13 años, dictándose leyes al respecto. La justicia luego de un debido proceso condenaba al victimario con reclusión incluso hasta la década del 70-80, con orquiectomía. Los adelantos en neurobiología, endocrinología, sicofarmacología y sicología se consideraron las bases para tratar al pedófilo y someterlo a libertad condicional, ahorrándose el costo financiero de la reclusión de por vida. Diversos países dictaron leyes contra la conducta pedófila. En dicha legislación ejerció gran influencia la promulgación en EE.UU. (estado de Washington "sobre el ofensor sexual" y el dictamen de la Corte Suprema en 1997 en el juicio de Kansas vs Hendricks). En Chile en los 90 el caso del pedófilo apodado "Zacarach" sacó a la luz pública el tema que no se quería ver. En esa fecha se presentó al parlamento un proyecto de Ley para "curar" la pedofilia con acetato de Medroxiprogesterona imitando legislación de EE.UU. Causó sorpresa en el medio endocrinológico que se usara terapia hormonal como "cura" de la pedofilia. Se ha utilizado en varios países la castración química producida por gestágenos o agonístas del GnRH más antiandrógenos (acetato de Ciproterona), para inhibir la secreción y acción de la testosterona disminuyendo líbido y erección. No se ha demostrado que exista curación de la orientación pedófila y existen dudas de la prevención primaria y secundaria de la pedofilia. Pese al adelanto tecnológico en neurociencias para estudio de las zonas vinculadas a la sexualidad, aún no existen marcadores que permitan diagnosticar o pronosticar futuros resultados de la terapia. El tratamiento médico de la pedofilia no garantiza curación ni prevención del delito pedofílico.

Historically, society has rejected sexual abuse of children under 13, with there having been laws enacted in this regard. The judicial system, after a due process, condemned the perpetrator with reclusion and even up until the decades of the 70s and 80s with orchiectomy. Advances in neurobiology, endocrinology, psychopharmacology and psychology were considered the basis for treating the pedophile and putting them on probation, saving the financial cost of imprisonment for life. Multiple countries have enacted laws against pedophilic behaviour. Such legislation was greatly influenced by the enactment in the USA (state of Washington "on the sex offender" and the ruling of the Supreme Court in 1997 in the trial of Kansas against Hendricks). In Chile in the 90s, the case of a pedophile nicknamed "Zacarach" brought to light an issue that nobody wanted to see. Around that time, a bill was presented to Parliament to try and "cure" pedophilia with Medroxyprogesterone acetate, imitating US legislation. It was a surprise in the endocrinological world that hormonal therapy would be used as a "cure" for pedophilia. Chemical castration produced by gestagens or GnRH agonists plus antiandrogens (Cyproterone acetate) has been used in several countries to inhibit the secretion and action of testosterone, reducing libido and erection. It has not been proven that there is a cure for pedophile orientation and there are doubts about the primary and secondary prevention of pedophilia. Despite technological advances in neurosciences for the study of the zones pertaining to sexuality, there are still no indicators that allow for diagnosis or prediction of future results of therapy. The medical treatment of pedophilia does not guarantee cure or prevention of pedophilic crime.

Para além da bula: experiências contraceptivas com o injetável trimestral / Beyond the medication package insert: contraceptive experiences with the quarterly injectable

O Acetato de Medroxiprogesterona de nome comercial Depo Provera é um contraceptivo injetável trimestral desenvolvido em meados do século XX, que esteve envolto em várias controvérsias relacionadas tanto com a descoberta do seu potencial como contraceptivo, quanto com a segurança do fármaco nas mulheres usuárias. Essa dissertação teve como objetivo compreender e analisar as experiências contraceptivas das mulheres com o contraceptivo injetável trimestral, através do exame das narrativas compartilhas no grupo de Facebook Anticoncepcionais Injetáveis: Dúvidas e Efeitos Colaterais inscrito em ambiente virtual de comunicação. A necessidade de compartilhar/adquirir informação com outras usuárias desta tecnologia tem encontrado um lugar importante no ciberespaço, especificamente nos grupos de Facebook, que permitem a divulgação de informações referentes à saúde da mulher e possibilitam a interação entre as participantes. O exame destas experiências é parte fundamental para entender o impacto do método na vida das mulheres 30 anos após a sua aprovação como contraceptivo pela FDA, em 1992. Foi realizado um estudo em contexto digital, com abordagem qualitativa, mediante compilação e análise de postagens entre novembro de 2020 a outubro de 2021, feitas por integrantes do grupo supracitado. Composto majoritariamente por mulheres jovens (com idade entre 18 a 34 anos) e moradoras do Brasil e Angola, as integrantes do grupo são usuárias do injetável trimestral e utilizam aquele espaço para compartilhar, sobretudo, preocupações em torno dos efeitos colaterais decorrentes do uso do método e pedir apoio sobre como proceder. Essa dissertação enfocou nas discussões a respeito da mudança nos padrões de menstruação, dos efeitos pós descontinuidade do método, e dos impactos do uso do injetável na sexualidade das usuárias que atinge especificamente a perda da libido, inclusive após a descontinuidade do método. Este trabalho também destaca a importância da qualidade das informações relacionadas à contracepção que são repassadas para as mulheres no âmbito da relação médicopaciente como ponto fundamental para a escolha informada em matéria contraceptiva.

Medroxyprogesterone Acetate, branded Depo Provera, is a quarterly injectable contraceptive developed in the mid-20th century, which was involved in several controversies related to both the discovery of its potential as a contraceptive, and the safety of the drug in women users. This dissertation aimed to understand and analyze the contraceptive experiences of women with the quarterly injectable contraceptive, by examining the narratives shared in the Facebook group Injectable Contraceptives: Doubts and Side Effects registered in a virtual communication environment. The need to share/acquire information with other users of this technology has found an important place in cyberspace, specifically in Facebook groups, which allow the dissemination of information regarding womens health and enable interaction between participants. Examining these experiences is a fundamental part of understanding the impact of the method on womens lives 30 years after its approval as a contraceptive by the FDA in 1992. A study was carried out in a digital context, with a qualitative approach, by compiling and analyzing posts between November 2020 to October 2021, made by members of the aforementioned group. Comprised mostly of young women (aged between 18 and 34) and residents of Brazil and Angola, the members of the group are users of the quarterly injectable and use that space to share, above all, concerns about the side effects resulting from the use of the method and ask for support on how to proceed. This dissertation focused on discussions about the change in menstruation patterns, the post-discontinuation effects of the method, and the impacts of the use of injectables on the sexuality of users that specifically affects the loss of libido, including post-discontinuity. This work also highlights the importance of the quality of information related to contraception that is passed on to women in the context of the doctor-patient relationship as a fundamental point for an informed choice in contraceptive matters.

Uterine secretory activity and histology of prepubertal female dogs in an animal model of partial ablation of endometrial glands development / Atividade secretória uterina e histologia de cadelas pré-púberes em um modelo animal de ablação parcial do desenvolvimento das glândulas uterinas

Inadequate exposure of the female reproductive system to steroids in uterine developmental periods can partially inhibit the development of endometrial glands in dogs. However, the effects of steroids on the formed glands functionality remain unknown, as well as the possible occurrence of endometrial fibrosis. This study aimed to evaluate the secretory activity of endometrial glands in prebubertal female dogs submitted to a protocol of partial ablation of the uterine adenogenesis. Sixteen females of non-specific breed were distributed into two groups; MPA (n=8), females that received applications of medroxyprogesterone acetate every 3 weeks; and C (n=8) untreated control females. Ovariohysterectomy was performed in all animals at the age of 6 months and evaluated the uterine horns by histological and histochemistry exams. The secretion intensity (degrees 1-4) was evaluated using periodic acid-Schiff (PAS) and alcian blue (AB) pH 2.5. Histological evaluation was performed using Masson's trichrome and toluidine blue. Only degree 1 and 2 marks for PAS were observed in both groups, with no difference of uterine secretion intensity between the groups regarding the degrees found. However, the MPA group revealed higher intensity of uterine secretion compared to group C (p<0.05). Staining with AB pH 2.5 also revealed only degree 1 and 2 marks in both groups, with no statistically significance between them. Masson's trichrome staining revealed no marks in the periglandular region in both groups. A higher among of mast cells was observed in the myometrial region of the uterus in both groups. Prepubertal female dogs with partial ablation of the uterine adenogenesis present minimal uterine secretory activity, absence of periglandular fibrosis and increased presence of mast cells in the myometrium compared to endometrium.(AU)

A exposição inadequada do sistema reprodutor feminino a esteróides em períodos do desenvolvimento uterino pode inibir parcialmente o desenvolvimento das glândulas endometriais em cães. Entretanto, não se conhece os efeitos dos esteróides sobre a funcionalidade das glândulas formadas, bem como a possível ocorrência de fibrose endometrial. Objetivou-se avaliar a atividade secretória das glândulas endometriais de cadelas pré-púberes submetidas a protocolo de ablação parcial da adenogênese uterina. Foram utilizadas 16 fêmeas, sem-raça-definida, distribuídas nos grupos MPA (n=8), fêmeas que receberam aplicações de acetato de medroxiprogesterona a cada 3 semanas, e C (n=8), fêmeas controle não tratadas. Aos seis meses de idade, foi realizada ovariohisterectomia em todos os animais, e avaliados os cornos uterinos pelo exame histológico e de histoquímica. Para avaliar a intensidade de secreção (graus 1-4), foram utilizadas periodic acid-Schiff e alcian blue (AB) pH 2,5. Para a avaliação histológica foram utilizados tricrômico de Masson e azul de toluidina. Apenas marcações graus 1 e 2 foram observadas para PAS em ambos os grupos, sem diferença na intensidade de secreção uterina entre grupos com relação aos graus encontrados. Entretanto, o grupo MPA apresentou maior intensidade de secreção uterina em relação ao grupo C (p<0,05). Com relação ao AB pH 2,5, em ambos os grupos também foram encontradas apenas marcações de graus 1 e 2, sem diferença estatística entre grupos. Não foram observadas marcações para a coloração de tricrômico de Masson na região periglandular, em ambos os grupos. Foi observada maior quantidade de mastócitos presentes no útero na região do miométrio, em ambos os grupos. Conclui-se que cadelas pré-púberes com ablação parcial da adenogênese uterina apresentam mínima atividade secretória uterina, ausência de fibrose periglandular e maior presença de mastócitos no miométrio em relação ao endométrio.(AU)

Six months response rate of combined oral medroxyprogesterone/levonorgestrel-intrauterine system for early-stage endometrial cancer in young women: a Korean Gynecologic-Oncology Group Study / 부인종양

OBJECTIVE: To evaluate the efficacy of combined oral medroxyprogesterone acetate (MPA)/levonorgestrel-intrauterine system (LNG-IUS) treatment and to compare the diagnostic accuracy of endometrial aspiration biopsy with dilatation & curettage (D&C) in young women with early-stage endometrial cancer (EC) who wished to preserve their fertility. METHODS: A prospective phase II multicenter study was conducted from January 2012 to January 2017. Patients with grade 1 endometrioid adenocarcinoma confined to the endometrium were treated with combined oral MPA (500 mg/day)/LNG-IUS. At 3 and 6 months of treatment, the histologic change of the endometrial tissue was assessed. The regression rate at 6 months treatment and the consistency of the histologic results between the aspiration biopsy and the D&C were evaluated. RESULTS: Forty-four patients were enrolled. Nine voluntarily withdrew and 35 patients completed the protocol treatment. The complete regression (CR) rate at 6 months was 37.1% (13/35). Partial response was shown in 25.7% of cases (9/35). There were no cases of progressive disease and no treatment-related complications. A comparison of the pathologic results from aspiration biopsy and D&C was carried out for 33 cases. Fifteen cases were diagnosed as “EC” by D&C. Among these, only 8 were diagnosed with EC from aspiration biopsy, yielding a diagnostic concordance of 53.3% (ĸ=0.55). CONCLUSION: Combined oral MPA/LNG-IUS treatment for EC showed 37.1% of CR rate at 6 months. Considering the short treatment periods, CR rate may be much higher if the treatment continued to 9 or 12 months. So, this treatment is still a viable treatment option for young women of early-stage EC. Endometrial aspiration biopsy with the LNG-IUS in place is less accurate than D&C for follow-up evaluation of patients undergoing this treatment. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01594879

Risks and benefits of menopausal hormone therapy

Menopausal hormone therapy (MHT) was widely used to improve quality of life by controlling menopausal symptoms, including vasomotor symptoms and urogenital atrophy. Furthermore, observational studies consistently reported beneficial effects of MHT on late problems of menopause, such as osteoporosis, coronary heart disease (CHD), and possibly dementia. However, circumstances changed abruptly after the 2002 publication of the first findings from the Women's Health Initiative (WHI) study, which was conducted in postmenopausal women (average age, 63 years) using conventional doses of conjugated equine estrogen (CEE) and medroxyprogesterone acetate. CEE with medroxyprogesterone acetate increased the risk of breast cancer and did not prevent CHD. However, CEE alone showed a tendency to decrease the risk of both breast cancer and CHD, with significant differences between the two therapies. A subgroup analysis by age and years since menopause led to a timing hypothesis regarding the effects of MHT on CHD. Indeed, CEE alone in women aged 50 to 59 significantly reduced CHD risk by 35% after 13 years of follow-up. In 2015, a Cochrane meta-analysis of MHT trials reported a 48% reduction in CHD, no change in stroke, and most importantly, a 30% decrease in total mortality in women with less than 10 years since menopause. Long-term follow-up of WHI participants confirmed beneficial impacts of CEE on breast cancer incidence and mortality. Further, fracture reduction in women with osteopenia was observed during the intervention phase of the WHI study. If initiated early after menopause, MHT could again be considered to improve menopause-related quality of life and decrease all-cause mortality.

Long-term outcomes of progestin plus metformin as a fertility-sparing treatment for atypical endometrial hyperplasia and endometrial cancer patients / 부인종양

OBJECTIVE: The present study investigated long-term outcomes of medroxyprogesterone acetate (MPA) plus metformin therapy in terms of control of atypical endometrial hyperplasia (AEH) and endometrial cancer (EC), and post-treatment conception. METHODS: We retrospectively analyzed 63 patients (42 with EC; 21 with AEH) who underwent fertility-sparing management using MPA plus metformin. MPA (400 mg/day) and metformin (750–2,250 mg/day) were administered to achieve complete response (CR). Metformin was administered until conception, even after MPA discontinuation. RESULTS: Of the total patients, 48 (76%) had a body mass index (BMI) ≥25 kg/m² and 43 (68%) showed insulin resistance. Sixty-one patients (97%) achieved CR within 18 months. CR rates at 6, 8–9, and 12 months were 60%, 84%, and 90%, respectively. During a median follow-up period of 57 months (range, 13–115 months), relapse occurred in 8 of 61 patients (13.1%) who had achieved CR. Relapse-free survival (RFS) in all patients at 5 years was 84.8%. Upon univariate analysis, patients with BMI ≥25 kg/m² had significantly better prognoses than did those with BMI <25 kg/m2 (odds ratio=0.19; 95% confidence interval=0.05–0.66; p=0.009). Overall pregnancy and live birth rates per patient were 61% (19/31) and 45% (14/31), respectively. CONCLUSIONS: MPA plus metformin is efficacious in terms of RFS and post treatment conception. Moreover, metformin may be more efficacious for patients with BMI ≥25 kg/m².

Predictors of fragility fracture and low bone mineral density in patients with a history of parental fracture

OBJECTIVES: Bone mineral density (BMD) and fragility fracture (FF) have high heritability, but few data exist on impact of other factors on families with fracture history. We aimed to evaluate predictors of FF and low BMD, in patients with family history of FF. METHODS: This was a retrospective study on patients undergoing dual energy X-ray absorptiometry at a district general hospital (DGH), 2004–2016. Parameters recorded (in addition to standard dual energy X-ray absorptiometry parameters): age, smoking, alcohol, corticosteroids, aromatase inhibitors, Depo-Provera, hormone replacement therapy, rheumatoid arthritis, polymyalgia rheumatica, breast or prostate cancer, coeliac disease, and fracture site. Logistic regression was used to model fracture risk and site, and linear regression for impact of factors on L1–4 and femoral BMD. Factor analyses with polychoric correlation matrices and calculation of Eigenvalues were applied to determine association between fracture sites and associated risk factors. RESULTS: A total of 6053 patients were included, 91.1% female. 2094 had sustained at least one FF. Smoking, alcoholism, increased age, height, and fat mass increased FF risk. Sites analysed: femur, tibia/fibula, humerus, forearm, ribs, and vertebrae. Alcoholism, and increasing tissue thickness and fat mass significantly increased FF risk. Decreased right femoral and vertebral BMD increased overall FF risk. CONCLUSIONS: Our study confirms the effect of certain factors on vertebral BMD, but suggests a differential effect on the upper and lower spine, as well as in the dominant and nondominant hip. Different sites of fracture are associated with different risk factors, the most common sites of fracture being the peripheral long bones and vertebrae.

The Women’s Health Initiative after 17 years: Has it done more harm than good? / Philippine Journal of Obstetrics and Gynecology

@#This commentary is focused primarily on the relationship between menopausal hormone therapy (MHT) and breast cancer risk, the primary adverse outcome measure of the Women’s Health Initiative (WHI) hormone trials. The WHI hormone trials are to date the largest randomized, placebo-controlled studies that evaluated the risks and benefits of hormone therapy in postmenopausal women. There are two arms: the estrogen-progestin (conjugated equine estrogen/medroxyprogesterone acetate) arm for women with intact uterus and the estrogen-alone (conjugated equine estrogen) arm for women who had a hysterectomy1. Both arms, planned to continue for 8.5 years, were stopped prematurely, the CEE/MPA arm after a mean of 5.2 years of follow-up and the CEE-alone arm after a mean of 7.2 years follow-up.

Effects of omega-6/3 and omega-9/6 nutraceuticals on pain and fertility in peritoneal endometriosis in rats

Abstract Purpose: To evaluate the effects of the nutraceuticals omega-6/3 and omega-9/6 on endometriosis-associated infertility and pain. Methods: Controlled experimental study, with each group composed of eight female rats. Fertility groups: sham-operated control (0.9% saline solution); control with endometriosis (0.9% saline); omega-6/3 (1.2 g/kg/day); omega-9/6 (1.2 g/kg/day); and meloxicam (0.8 mg/kg/day). Pain groups: sham-operated control (0.9% saline); control with endometriosis (0.9% saline); omega-6/3 (1.2 g/kg/day); omega-9/6 (1.2 g/kg/day); medroxyprogesterone acetate (5 mg/kg/every 3 days); and meloxicam (0.8 mg/kg/day). Peritoneal endometriosis was surgically induced. Pain was evaluated with the writhing test. Fertility was evaluated by counting the number of embryos in the left hemi-uterus. Results: The mean number of writhings was as follows: sham-operated, 11.1 ± 2.9; control with endometriosis, 49.3 ± 4.4; omega-6/3, 31.5 ± 2.7; omega-9/6, 34.1 ± 4.5; medroxyprogesterone acetate, 2.1 ± 0.8; meloxicam, 1 ± 0.3. There was a significant difference between both controls and all drugs used for treatment. Regarding fertility, the mean values were as follows: sham-operated, 6.8 ± 0.6; control with endometriosis, 4.2 ± 0.7; omega-6/3, 4.7 ± 1; omega-9/6, 3.8 ± 0.9; and meloxicam, 1.8 ± 0.9. Conclusions: The omega-6/3 and omega-9/6 nutraceuticals decreased pain compared to the controls. There was no improvement in fertility in any of the tested groups.

Dietary intake and eating behavior in depot medroxyprogesterone acetate users: a systematic review

Because of weight gain, women often discontinue hormonal contraception, especially depot medroxyprogesterone acetate (DMPA). Our objective was to conduct a systematic review of studies describing dietary intake or eating behavior in DMPA users to understand whether the use of DMPA is associated with changes in dietary habits and behaviors leading to weight gain. We searched the PubMed, POPLINE, CENTRAL Cochrane, Web of Science, and EMBASE databases for reports published in English between 1980 and 2017 examining dietary intake or eating behavior in healthy women in reproductive age and adolescents using DMPA (150 mg/mL). Of the 749 publications screened, we excluded 742 due to duplicates (96), not addressing the key research question (638), not reporting dietary intake data (4), and not evaluating the relationship of body weight and dietary or eating behaviors (4). We identified seven relevant studies, including one randomized placebo-controlled trial, one non-randomized paired clinical trial, and five cohort studies. The randomized trial found no association and the other reports were inconsistent. Findings varied from no change in dietary intake or eating behavior with DMPA use to increased appetite in the first six months of DMPA use. Few studies report dietary intake and eating behavior in DMPA users and the available data are insufficient to conclude whether DMPA use is associated with changes in dietary habits or behavior leading to weight gain.

Is repeated high-dose medroxyprogesterone acetate (MPA) therapy permissible for patients with early stage endometrial cancer or atypical endometrial hyperplasia who desire preserving fertility? / 부인종양

OBJECTIVE: Reports on the repeated administration of medroxyprogesterone acetate (MPA) for intrauterine recurrence after fertility-preserving therapy for atypical endometrial hyperplasia (AEH) and early grade 1 endometrioid carcinoma (G1) are lacking. We aimed to clarify the outcomes of repeated MPA therapy in cases of intrauterine recurrence after fertility-preserving therapy with MPA against AEH/early G1. METHODS: Patients with AEH or stage IA well-differentiated endometrioid carcinoma without myometrial invasion who underwent first-line MPA therapy for primary lesions or intrauterine recurrence were divided into initial treatment and repeated treatment groups (162 and 82 patients, respectively). Oral MPA administration (400−600 mg/day) was continued until pathological tumor disappearance. Data regarding clinicopathological factors, adverse events, and outcomes following the initial and repeated hormonal treatments were extracted from medical records and analyzed. RESULTS: Complete response rates in the initial and repeated treatment groups were 98.5% and 96.4%, respectively, among patients with AEH, and were 90.7% and 98.1%, respectively, among patients with G1. In the initial treatment group, 5-year recurrence-free survival (RFS) rates were 53.7% and 33.2% among patients with AEH and G1, respectively. In the repeated treatment group, RFS rates were 14.0% and 11.2% among patients with AEH and G1, respectively. Among patients with AEH, the pregnancy rate tended to be lower in the repeated treatment group than in the initial treatment group (11.1% vs. 29.2%; p=0.107), while no significant group difference was observed among patients with G1 (20.8% vs. 22.7%). CONCLUSION: Repeated treatment is sufficiently effective for intrauterine recurrence after hormonal therapy for AEH/early G1.

Avaliação de parâmetros metabólicos e marcadores de doença cardiovascular subclínica em novas usuárias não obesas do contraceptivo de acetato de medroxiprogesterona de depósito / Evaluation of metabolic parameters and markers of subclinical cardivascular desease in new and non-obese users of depot medroxyprogesterone acetate contraceptive

Resumo: As doenças cardiovasculares (DCV) estão entre as principais causas de mortalidade global. Nos Estados Unidos as taxas de mortalidade por DCV em mulheres nas faixas de idade de 35-54 anos não têm mostrado a redução esperada. O numero de mulheres nos estudos ainda é pequeno e falta conhecimento sobre o impacto na saúde cardiovascular dos ciclos gestacionais e do uso de compostos hormonais para contracepção/terapias por períodos longos. Objetivos: avaliar o metabolismo de carboidratos e marcadores de DCV em mulheres não obesas saudáveis durante o primeiro ano de uso do contraceptivo de acetato de medroxiprogesterona de depósito (AMPD). Métodos: estudo prospectivo não randomizado, comparativo, conduzido no Ambulatório de Planejamento Familiar e no Serviço de Ecografia do Departamento de Obstetrícia e Ginecologia da Faculdade de Ciências Médicas/UNICAMP, entre 02/2011 e 02/2013. Mulheres com 18-40 anos e índice de massa corporal (IMC) <30 kg/m2, recrutadas a partir de Unidades Básicas de Saúde, realizaram teste de pós-carga com 75 mg glicose via oral (OGTT). Foram incluídas aquelas que apresentaram OGTT normal e assinaram Termo de Consentimento Livre e Esclarecido. Os critérios de exclusão foram diagnóstico/antecedente de Diabete Melittus, período de aleitamento, hipertensão arterial, hiper/hipotiroidismo, insuficiência renal crônica, hirsutismo/hiperandrogenismo, Síndrome do Ovário Policístico, uso crônico de corticosteróides, antipsicóticos, tiazídicos e estatinas, antecedente de transplante de órgão, cirurgia bariátrica e omentectomia. As mulheres puderam escolher utilizar o AMPD ou o dispositivo intrauterino com cobre (DIU) e compuseram dois grupos pareados por idade (±1) e IMC (±1), seguidos durante 12 meses. Realizou-se avaliação de peso, IMC, composição corporal por densitometria (DXA), medidas da cintura, pressão arterial e ultrassonográficas da espessura da intima-media da artéria carótida e dos compartimentos de gordura abdominal (GA), dosagens séricas dos perfis glicêmico e lipídico, ácidos graxos livres, apolipoproteínas A1 e B-100, adipocinas IL-6, TN-alfa, leptina, adiponectina, PCR e cálculo do índice HOMA. Resultados: Apresentaram-se 290 mulheres, 72 com critérios para inclusão e 56 (31 grupo AMPD e 25 DIU) foram analisadas com relação ao metabolismo de carboidratos, semestralmente. O grupo AMPD mostrou elevação nos níveis séricos de insulina, HOMA, circunferência da cintura e IMC, quando comparado ao grupo DIU. Analisando-se as 30 mulheres sem resistência insulínica, o grupo AMPD mostrou aumento de triglicérides aos 12 meses em relação ao grupo DIU. Entre 37 mulheres, as medidas ultrassonográficas de GA, realizadas no basal e aos 12 meses, apresentaram forte correlação com as medidas de composição corporal e antropométricas, e com as concentrações séricas de colesterol total, LDL colesterol, APO B-100 e PCR. Conclusões: Não foram observados efeitos cardiovasculares significativos no primeiro ano de uso do AMPD nesta amostra; o aumento de triglicérides foi interpretado como variação provocada por alterações no metabolismo da glicose. HOMA, peso corporal e circunferência da cintura foram parâmetros clínicos importantes para o monitoramento das usuárias de AMPD. A ultrassonografia poderá ser ferramenta viável para identificar indivíduos com aumento de gordura corporal e risco cardiovascular; sendo necessários estudos futuros para confirmação desses resultados, padronização de locais de aferição e pontos de corte relacionados ao possível risco para DCV(AU)

Abstract: One of the main causes of global death is cardiovascular disease (CVD). In the United State of America the mortality rates have not decreased as expected in women between 35 and 54 years old. In general, the studies are performed with a small number of women in the sample composition and lack knowledge about specifically female characteristics and their interaction in cardiovascular health, such as the use of hormonal contraceptives for a prolonged time. Objectives: To evaluate carbohydrate metabolism and markers of CVD in the first year of depot medroxyprogesterone acetate (DMPA) for contraceptive use. Methods: Prospective, not randomized comparative study conducted in the Family Planning Clinic and Ultrasound Unit of the Department of Obstetrics and Gynecology, University of Campinas Medical School, between 02/2011-02/2013. Women aged 18-40 years and body mass index (BMI) <30 kg/m2, recruited from Basic Health Units, performed a post-load test with 75 mg oral glucose (OGTT). Those that presented normal OGTT and agreed to participate were included in the study. The exclusion criteria were diagnosis/history of diabetes mellitus, lactation period, hypertension, hyper/hypothyroidism, chronic renal failure, hirsutism/hyperandrogenism, polycystic ovarian syndrome, chronic use of corticosteroids, antipsychotics, thiazides and statins, history of organ transplantation, bariatric surgery and omentectomy. Women were able to choose to use the DMPA or copper intrauterine device (IUD) and composed two matched groups by age (±1) and BMI (±1), followed for 12 months. Were evaluated weight, BMI, body composition (BC), waist circumference, blood pressure and ultrasound measurements of the carotid intimal medial thickness and abdominal fat compartments (AF), serum levels of lipid and glycemic profiles, free fatty acids, apolipoproteins A-1 and B-100, adipokines IL-6, TN-alpha, leptin, adiponectin, C-reactive protein (CRP) and HOMA index, at baseline and 12 months. Results: 290 women were enrolled, of which 72 met the criteria for inclusion and only 56 women (31-DMPA group and 25-IUD group) were analyzed with regard to carbohydrate metabolism at baseline and after 6 and 12 months. The DMPA group showed elevated serum levels of insulin, HOMA, waist circumference and BMI when compared to the IUD group. The analysis of 30 women without insulin resistance, diagnosed by hyperinsulemic euglycemic clamp, the DMPA group showed increase of triglycerides at 12 months when compared to the IUD group. Among 37 women, ultrasonography measurements of AF at baseline and 12 months showed a strong correlation with BC and anthropometric measurements, and serum concentrations of total cholesterol, LDL- chol, APO B-100 and CRP. Conclusions: No significant cardiovascular effects were observed in the first year of DMPA use in this sample; the increase in triglycerides was interpreted as a variation caused by changes in glucose metabolism. HOMA, body weight and waist circumference were important clinical parameters for the monitoring of DMPA users. Ultrasonography may be a viable tool to identify individuals with increased body fat and cardiovascular risk and future studies are required to confirm these results, to standardize measurement sites and cut-off points related to the possible risk for CVD(AU)

Quantitative analysis of collagen fibrillar structure in canine uterus exposed to acetate of medroxyprogesterone using second harmonic generation microscopy / Análisis cuantitativo de la estructura de fibras colágenas en útero canino expuesto a acetato de medroxiprogesterona utilizando generación microscópica de un segundo harmónico

Collagen is the most abundant structural protein found in organs and is responsible for providing tissues with structure and function. In order to investigate in canine uteri the potential effect of medroxyprogesterone acetate (MPA) on the changes in collagen deposition were grouped as nulliparous (n=11), multiparous (n=11) and treated with MPA (n=11; nulliparous with two treatments; 5 mg/kg; i.m.). The amount of collagen was studied in the fold and basal regions of the endometrium and myometrium using second harmonic generation with a two-photon spectral confocal microscope, quantified using ImageJ software with a color segmentation plugin, was expressed as fraction area (%) and analyzed by ANOVA (p<0,05). No differences were observed between groups in the fold (p=0,3995) or base (p=0,7392) of the endometrium and myometrium (p=0,1781). In conclusion, our data demonstrate that two doses of MPA (5 mg/kg; i.m.) do not affect the total collagen deposition in canine uteri undergoing contraceptive treatment.

El colágeno es la proteína estructural más abundante presente en órganos y es responsable de proporcionar la sostén y función a los tejidos. Para investigar en caninos el efecto potencial del acetato de medroxiprogesterona (MPA) sobre cambios en el depósito de colágeno en útero, éstos fueron agrupados como nulíparos (n = 11), multíparos (n = 11) y tratados con MPA (n = 11, nulíparos con dos tratamientos 5 mg/kg, im). El colágeno fue evaluado en el pliegue y regiones basales del endometrio y en miometrio utilizando la Generación de un Segundo Harmónico con un microscopio confocal espectral y dos fotones y cuantificado utilizando el software ImageJ a partir de la segmentación de colores. Los resultados fueron expresados y analizados como fracción de área (%; ANOVA; p<0,05). No se observaron diferencias entre los grupos en el pliegue (p = 0,3995) y base (p=0,7392) del endometrio y tampoco en miometrio (p=0,1781). En conclusión, nuestra evidencia demuestra que dos dosis de MPA (5 mg/kg, i.m.) no afectan el depósito total de colágeno en úteros caninos expuestos a tratamiento anticonceptivo.

Body composition, resting energy expenditure and inflammatory markers: impact in users of depot medroxyprogesterone acetate after 12 months follow-up

ABSTRACT Objective The aim of this study was to evaluate for 12 months the changes of body weight using Depot Medroxyprogesterone Acetate (DMPA) and if these changes are related to inflammatory markers. Subjects and methods Twenty women of childbearing age who chose the DMPA, without previous use of this method, BMI < 30 kg/m2, and 17 women using IUD TCu 380A, participated in the study. At the baseline and after one year, changes in weight gain, body composition by the bioimpedance electric method, resting energy expenditure (REE) by the indirect calorimetry method, inflammatory markers and HOMA-IR were assessed. Results After 12 months of evaluation, we could observe a significant increase in the DMPA group in weight (3,01 kg) and BMI, while the IUD group’s only significant increase was observed in the BMI. Relative to REE there was an increase of basal metabolic rate (BMR) in both groups after one year. The sub-group DMPA that gained < 3 kg had increased significant weight, BMI and body surface (BS) with respiratory quotient (RQ) reduction, while the sub-group that gained ≥ 3 kg had a significant increase in weight, BMI, BS, fat-free mass, fat mass, BMR, Leptin, HOMA-IR and waist circumference, with RQ significantly reduced. Conclusion Our study found significant changes in weight, body composition and metabolic profile of the population studied in the first 12 months of contraceptive use. These changes mainly increased body weight, leptin levels and HOMA-IR which can contribute to the development of some chronic complications, including obesity, insulin resistance and diabetes mellitus.

A case report on catamenial epilepsy / Philippine Journal of Obstetrics and Gynecology

A case of a 17-year-old nulligravid with onset of seizure episodes since menarcheis reported. She was diagnosed with Seizure Disorder treated with Phenobarbital and was seizure free for 2 years. Two years prior to consult, seizure recurrences were noted to coincide with menstruation, hence, was diagnosed with Catamenial Epilepsy. Patient was shifted to Lamotrigine but seizure exacerbations were still observed, prompting referral to the Reproductive Medicine service for adjunctive hormonal therapy. Depot medroxyprogesterone acetate was added to the antiepileptic drug which provided seizure control. Adjunctive hormonal therapy proved to be helpful in the management of intractable seizures in this patient. The report aims to give a better understanding of the neuroactive properties of estrogen and progesterone and its role in the development of Catamenial Epilepsy. Gender-related and psychosocial issues in the treatment of Epilepsy in the child-bearing years up to the menopause are also discussed.