Progestinas y cáncer de mama en terapia de reemplazo hormonal: cómo actúan y qué alternativas son más seguras / Progestins and breast cancer in hormone replacement therapy: how do they work, and what alternatives are safer

En algunos estudios se ha asociado a la terapia de reemplazo hormonal (TRH) con estrógenos y progestinas a un mayor riesgo de cáncer de mama que la terapia con estrógenos solos. Sin embargo, dependiendo de su naturaleza algunas progestinas serían más seguras que otras. Se buscaron y analizaron artículos atingentes al tema en las bases de datos Google Scholar, PubMed, Science, SciELO y Cochrane, introduciendo los siguientes términos: terapia de reemplazo hormonal y cáncer de mama, progestinas y cáncer de mama, receptor de progesterona. Específicamente se ha asociado a las progestinas sintéticas acetato de medroxiprogesterona, noretisterona y levonorgestrel con un mayor riesgo de cáncer de mama, no así a la progesterona natural, a la progesterona oral micronizada ni a la didrogesterona. La progesterona natural, progesterona micronizada y didrogesterona serían más seguras en TRH para evitar el desarrollo de cáncer de mama, lo que estaría dado por la mayor especificidad en su acción.

In some studies, hormone replacement therapy (HRT) with estrogens and progestins has been associated with a higher risk of breast cancer than therapy with estrogens alone. However, depending on their nature, some progestins may be safer than others. This article analyzes the mode of action of progesterone in breast tissue and also the role of some progestins in the development of this pathology. Articles related to the subject were searched for and analyzed in Google Scholar, PubMed, Science, SciELO and Cochrane databases, introducing the following terms: hormone replacement therapy and breast cancer, progestins and breast cancer, progesterone receptor. Specifically, synthetic progestins medroxyprogesterone acetate, norethisterone, and levonorgestrel have been associated with an increased risk of breast cancer, but not natural progesterone, micronized oral progesterone, or dydrogesterone. Natural progesterone, micronized progesterone and dydrogesterone would be safer in HRT to prevent the development of breast cancer, which would be due to the greater specificity of their action.

Usos não contraceptivos dos fármacos anticoncepcionais orais hormonais: uma revisão / Non-contraceptive uses of hormonal oral contraceptive drugs: a review

Introdução: os anticoncepcionais orais 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 orais 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. Neste último, exercem um efeito protetor durante anos, até mesmo após a interrupção. Conclusão: assim, os anticoncepcionais orais hormonais têm representado uma nova proposta terapêutica simples, segura e eficaz, para diversas utilidades não contraceptivas, e seus benefícios ultrapassam os riscos associados, proporcionando uma terapia adequada e individualizada para cada mulher.

Introduction: hormonal oral contraceptives are drugs consisted by hormones, usually combined, estrogen and progestogen, or just progestins. Due to the characteristic properties of these hormones, they are also responsible for several side effects, which has led to a continuous evolution of the formulations and various non-contraceptive benefits to women's health have been observed. Objective:the objective of this review was to analyze the non-contraceptive uses of hormonal oral contraceptives, showing their effectiveness and safety. Methodology: the research was conducted in electronic databases and search portals, prioritizing materials published in the annual range from 2008 to 2018, with 332 found and 148 study materials used. Results: these drugs have been an effective alternative for the treatment of polycystic ovary syndrome, since they reduce circulating androgens and induce improvement in symptoms such as acne, menstrual irregularity and dysmenorrhea. They are associated with the treatment of endometriosis and a lower incidence of ovarian cancer. In the latter, they have a protective effect for years, even after the interruption. Conclusion: thus, hormonal oral contraceptives have represented a new simple, safe and effective therapeutic proposal, for several non-contraceptive uses, and their benefits outweigh the associated risks, providing an adequate and individualized therapy for each woman

Does a single application of contraceptive cause pathological changes in bitches? / [Uma única aplicação de anticoncepcional causa alterações patológicas em cadelas?]

O presente trabalho objetivou avaliar os efeitos da administração em dose única de progestágenos em fêmeas caninas hígidas, as quais nunca haviam recebido tais fármacos. Foram selecionadas 20 cadelas, que foram examinadas clinicamente e por meio de exames complementares. Nessas cadelas, foi aplicado medroxiprogesterona por via subcutânea. Noventa dias após, as fêmeas foram esterilizadas cirurgicamente, sendo os tecidos reprodutivos encaminhados para histopatologia. Foi possível verificar que, aos 30 dias, 12 animais (60%) apresentaram hiperplasia mamária. Aos 90 dias, 18 animais (90%) apresentavam sinais de hiperplasia endometrial cística, tendo cinco (27,77%) destes animais apresentado conteúdo purulento no lúmen uterino. No exame microscópico, apenas uma fêmea não demonstrou alterações patológicas, sendo a única que recebeu o contraceptivo na fase correta (anestro). As demais fêmeas apresentaram alterações que variaram entre alterações circulatórias a hiperplasia endometrial cística grave. Assim, foi possível concluir que uma única aplicação de anticoncepcional em fêmeas hígidas pode causar complicações leves a graves.(AU)

Fertility preservation in breast cancer with oral progestin: is it an option? A pilot study / Preservação da fertilidade com progestágeno oral em pacientes com câncer de mama: é uma opção? Estudo-piloto

ABSTRACT Objective To compare the effectiveness of oral progestins and injectable gonadotropin-releasing hormone antagonist medication in cancer fertility preservation in patients with breast cancer. Methods A cross-sectional study with 40 breast cancer patients submitted to cancer fertility preservation, who were divided into two groups according to histochemical analysis of progesterone receptors to define luteinizing hormone block: if positive, use of gonadotropin-releasing hormone antagonist, if negative, use of oral progestins. The mean age, medication days, antral follicle count, number of oocytes in metaphase II and the occurrence of ovarian hyperstimulation syndrome were compared. Results A total of 20 patients both in the group using gonadotropin-releasing hormone antagonist, and in the group with oral progestins, respectively, had a mean age of 33.9 (32-35.8) and 33.8 (32-35.6) years; days of medications of 11 (9.7-12.3) and 12.8 (11.6-13.9), p=0.037; antral follicle count of 9 (7.11-12) and 8.5 (6-11.9), p=0.370; metaphase II oocyte number of 4 (2.1-9.8) and 7.5 (3.1-10), p=0.348; and ovarian hyperstimulation syndrome of 2 (10%) and 5 (25%) cases, p=0.212. Conclusion The use of oral progestins, in spite of requiring longer treatment time, is effective in relation to the protocol with gonadotropin-releasing hormone antagonist, and offers greater comfort at a lower cost in breast cancer patients with negative progesterone receptors, submitted to cancer fertility preservation.

RESUMO Objetivo Comparar a efetividade dos progestágenos orais em relação à medicação injetável antagonista de hormônio liberador de gonadotrofina na preservação da fertilidade oncológica de pacientes com câncer de mama. Métodos Estudo transversal com 40 pacientes com câncer de mama submetidas à preservação da fertilidade oncológica, que foram divididas em dois grupos, conforme análise histoquímica dos receptores de progesterona, para definir o bloqueio de hormônio luteinizante: se positivos, uso de antagonista de hormônio liberador de gonadotrofina; se negativos, uso de progestágenos orais. Comparou-se média de idade, dias de medicações, contagem de folículos antrais, número de oócitos em metáfase II e ocorrência de síndrome do hiperestímulo ovariano. Resultados Vinte pacientes, tanto no grupo com uso de antagonista de hormônio liberador de gonadotrofina, quanto no grupo com progestágenos orais, respectivamente, apresentaram média de idade de 33,9 (32-35,8) e 33,8 (32-35,6) anos; 11 (9,7-12,3) e 12,8 (11,6-13,9) de dias de medicações com p=0,037; contagem de folículos antrais de 9 (7,11-12) e 8,5 (6-11,9), com p=0,370; número de oócitos metáfase II de 4 (2,1-9,8) e 7,5 (3,1-10), com p=0,348, e síndrome do hiperestímulo ovariano de 2 casos (10%) e 5 casos (25%), com p=0,212. Conclusão O uso de progestágenos orais, apesar de necessitar de maior tempo de tratamento, é efetivo em relação ao protocolo com antagonista de hormônio liberador de gonadotrofina e oferece maior conforto com menor custo em pacientes com câncer de mama com receptores de progesterona negativos, submetidas à preservação da fertilidade oncológica.

GnRH-a combined fertility-sparing re-treatment in women with endometrial carcinoma or atypical endomertial hyperplasia who failed to oral progestin therapy / 中华妇产科杂志

Objective:To analyze the clinical efficacy and pregnancy outcomes of gonadotropin-releasing hormone agonist (GnRH-a) based fertility-sparing re-treatment in women with endometrial carcinoma (EC) and atypical endometrial hyperplasia (AEH) who failed with oral progestin therapy.Methods:Forty cases with EC or AEH who failed to respond to oral progestin were included from January 2012 to December 2020 at Peking Union Medical College Hospital. Combination of GnRH-a with levonorgestrel-releasing intrauterine system (group GLI: a subcutaneous injection of GnRH-a every 4 weeks and LNG-IUS insertion constantly) or the combination of GnRH-a with aromatase inhibitor (group GAI: a subcutaneous injection of GnRH-a every 4 weeks and oral letrozole 2.5 mg, daily) were used for these patients. Histological evaluation were performed at the end of each course (every 3-4 months) by hysteroscopy and curettage. After the complete remission (CR), all patients were followed up regularly.Results:(1) Clinical characteristics:among the 40 patients with EC or AEH, the median age at diagnosis was 31 years (range: 22-40 years) and the median body mass index was 24.7 kg/m 2 (range: 18.9-39.5 kg/m 2). (2) Efficacy of fertility-sparing re-treatment: 37 (92%, 37/40) patients achieved CR, 6 (6/7) in AEH and 31 (94%, 31/33) in EC patients. The CR rate was 93% (26/28) and 11/12 in group GLI and GAI, respectively. The median time to CR was 5 months (range: 3-12 months). At the end of the first therapy course, the CR rates in AEH and EC were 5/7 and 42% (14/33), at the second course, the CR rates were 6/7 and 82% (27/33), respectively. (3) Recurrence: after 25 months of median follow-up duration (range: 10-75 months), 8 (22%, 8/37) women developed recurrence, 1/6 in AEH and 7 (23%, 7/31) in EC patients, with the median recurrence time of 18 months (range: 9-26 months). Among them, two cases who had completed childbirth chose to receive hysterectomy directly. Six patients met the criteria of fertility-preserving therapy and received conservative treatment again and 5 (5/6) of them achieved CR. (4) Pregnancy: of the 37 patients with CR, 33 desired to conceive. Ten women attempted to get pregnancy spontaneously and 23 cases with assisted reproductive technology. Fourteen (42%, 14/33) patients became pregnant, including 9 (27%, 9/33) live births, 3 (9%, 3/33) missed abortions, and 2 (6%, 2/33) miscarriages at the second trimester. Conclusions:GnRH-a based fertility-sparing re-treatment in AEH or EC patients who failed with oral progestin therapy achieved good treatment effect and reproductive outcomes. It is an encouraging alternative regime for patients who failed with oral progestin therapy.

Clinical efficacy and pregnancy outcomes of fertility-preserving re-treatment after recurrence of the patient with atypical endometrial hyperplasia and early stage endometrial carcinoma / 中华妇产科杂志

Objective@#To analyze the clinical efficacy and pregnancy outcomes of fertility- preserving re-treatment in patients with recurrent atypical endometrial hyperplasia (AEH) and early stage endometrial carcinoma (EEC) after achieved complete remission (CR) of primary fertility-preserving therapy.@*Methods@#There were 104 cases of AEH and EEC collected from 9 hospitals in the multi-center research network platform of fertility-preserving therapy of endometrial carcinoma in China from January 2005 to May 2019. Thirth-one cases of them relapsed from four hospitals mentioned above,who achieved CR after primary fertility-preserving therapy,was analyzed retrospectively. Of the 31 cases, 27 cases chose fertility-preserving re-treatment. The demographic characteristics, re-treatment effect, clinical factors and pregnancy outcomes were observed.@*Results@#(1) There were 16 AEH cases and 11 ECC cases among 27 recurrent patients who chose fertility-preserving therapy again. After re-treatment, CR was found in 13 out of 16 cases of AEH and 9 out of 11 cases of EEC. The overall CR rate was 81% (22/27). (2) After CR of recurrence, 5 cases (23%, 5/22) of re-recurrence were found after with a median time of 33 months (range 21-80 months). There were 4 cases underwent comprehensive surgical staging, and 1 patient chose the third round of fertility preservation therapy with fully informed consent, and CR was reached after 15 months. (3) There were 16 cases with pregnancy intention, with a total of 12 pregnancies, including 5 cases were natural pregnancy and 7 cases were assisted reproductive technology pregnancy. There were 5 live births. The follow-up time was up to May 2019, and the median follow-up time was 73 months (range 0-123 months). All 27 patients had disease free survival.@*Conclusions@#Recurrent patients with AEH and EEC after achieving successful fertility-preserving therapy could choose fertility-preserving therapy again with comprehensive assessment and fully informed consent. After re-treatment, there is a certain tumor CR rate and pregnancy rate, while the close follow-up is required during treatment.

Combined estrogen-progestin pill is a safe and effective option for endometrial hyperplasia without atypia: a three-year single center experience / 부인종양

OBJECTIVE: To evaluate the effectiveness of oral contraceptive pill (OCP) as therapy for endometrial hyperplasia (EH) without atypia in reproductive-aged women compared with oral progestin. METHODS: A retrospective cohort study was carried out in our reproductive center. Consecutive patients diagnosed with infertility and non-atypical EH identified through electronic database who met inclusion criteria (n=309). Patients were assigned to two treatment groups: OCP (n=216) and oral progestin (n=93); clinical and reproductive outcomes were recorded. RESULTS: Reversal of EH to normal endometrium, clinical pregnancy, live birth and miscarriage rate. Women in OCP group were younger, had higher prevalence of Polycystic Ovary Syndrome and other uterine pathology and longer duration of infertility than women in progestin group. Reversal of EH was observed in 93.52% women on OCP and in 86.02% women on progestin (p=0.032; adjusted odds ratio [aOR]= 2.35; 95% confidence interval [CI]=1.06-5.21) after the initial course of treatment for 2 to 6 months. Cyclic OCP (n=184) resulted in better response to treatment compared to continuous OCP (n=32) (95.11% vs. 84.38%; p=0.039; aOR =3.60; 95% CI =1.12-11.55). Clinical pregnancy rate in OCP group was marginally higher than progestin group (87/208, 41.83% vs. 27/90, 30.00%; p=0.054). Miscarriage (25.29% vs. 29.63%; p=0.654) and live birth rate (31.25% vs. 21.11%; p=0.074) were comparable between the groups. CONCLUSION: For the first time we demonstrate that OCP is an effective therapy for non-atypical EH and is associated with higher remission rate compared with oral progestin. Reproductive outcomes are reassuring and comparable between the two groups.

Hormone treatment as first line therapy is safe and relieves pelvic pain in women with bowel endometriosis / O tratamento hormonal como terapia de primeira linha é seguro e melhora a dor pélvica em mulheres com endometriose intestinal

ABSTRACT Objective: To evaluate clinical features and complications in patients with bowel endometriosis submitted to hormonal therapy. Methods: Retrospective study based on data extracted from medical records of 238 women with recto-sigmoid endometriosis treated between May 2010 and May 2016. Results: Over the course of follow-up, 143 (60.1%) women remained in medical treatment while 95 (39.9%) presented with worsening of pain symptoms or intestinal lesion growth (failure of medical treatment group), with surgical resection performed in 54 cases. Women in the Medical Treatment Group were older (40.5±5.1 years versus 37.3±5.8 years; p<0.0001) and had smaller recto sigmoid lesions (2.1±1.9 versus 3.1±2.2; p=0.008) compared to those who had failed to respond to medical treatment. Similar significant reduction in pain scores for dysmenorrhea, chronic pelvic pain, cyclic dyschezia and dysuria was observed in both groups; however greater reduction in pain scores for dyspareunia was noted in the Surgical Group. Subjective improvement in pain symptoms was also similar between groups (100% versus 98.2%; p=0.18). Major complications rates were higher in the Surgical Group (9.2% versus 0.6%; p=0.001). Conclusion: Patients with recto-sigmoid endometriosis who failed to respond to medical treatment were younger and had larger intestinal lesions. Hormonal therapy was equally efficient in improving pain symptoms other than dyspareunia compared to surgery, and was associated with lower complication rates in women with recto-sigmoid endometriosis. Medical treatment should be offered as a first-line therapy for patients with bowel endometriosis. Surgical treatment should be reserved for patients with pain symptoms unresponsive to hormonal therapy, lesion growth or suspected intestinal subocclusion.

RESUMO Objetivo: Avaliar características clínicas e complicações em pacientes com endometriose intestinal submetidos ao tratamento hormonal. Métodos: Dados de prontuários de 238 pacientes com endometriose de retossigmoide tratadas entre maio de 2010 e maio de 2016 foram coletados para este estudo retrospectivo. Resultados: Durante o período de acompanhamento, 143 (60,1%) mulheres mantiveram tratamento clínico, enquanto 95 (39,9%) tiveram piora dos sintomas de dor ou aumento da lesão intestinal (grupo falha de tratamento clínico), sendo 54 submetidas ao tratamento cirúrgico. As mulheres no Grupo Tratamento Clínico eram mais velhas (40,5±5,1 anos versus 37,3±5,8 anos; p<0,0001) e tinham lesões intestinais menores (2,1±1,9 versus 3,1±2,2; p=0,008) em comparação ao grupo falha de tratamento clínico. Redução significativa e semelhante do escore de dor na dismenorreia, dor pélvica crônica, disquezia cíclica e disúria cíclica foi observada nos Grupos Tratamento Clínico e Cirúrgico. Dispareunia, no entato, teve uma redução maior no Grupo Cirurgia. A redução subjetiva dos sintomas dolorosos também foi semelhante entre os Grupos Clínico e Cirúrgico (100% versus 98,2%; p=0,18). O Grupo Tratamento Cirúrgico foi relacionado a uma maior taxa de complicações graves (9,2% versus 0,6%; p=0,001) em comparação ao Grupo Tratamento Clínico. Conclusão: Falha no tratamento clínico em pacientes com endometriose de retossigmoide foi observada em mulheres mais jovens que tinham lesões intestinais maiores. O tratamento clínico hormonal foi igualmente eficaz na melhora dos sintomas de dor, exceto dispareunia, em comparação ao tratamento cirúrgico em mulheres com endometriose intestinal, mas com menor taxa de complicações. O tratamento clínico deve ser oferecido como primeira opção em pacientes com endometriose intestinal, enquanto o tratamento cirúrgico deve ser reservado para pacientes sem melhora nos sintomas de dor com tratamento hormonal, progressão das lesões ou suspeita de suboclusão intestinal.

Consecuencias oncológicas y perinatales del tratamiento conservador de la fertilidad en pacientes con cáncer endometrial tratadas con progestinas / Oncological and perinatal results of conservative treatment of fertility in patients with endometrial cancer treated with progestins

Resumen OBJETIVO: Estimar la tasa de respuesta completa y de embarazo en mujeres con cáncer endometrial en tratamiento conservador con progestinas. MATERIALES Y MÉTODOS: Estudio de cohorte, retrolectivo y transversal efectuado en el Instituto Nacional de Perinatología en mujeres con cáncer endometrial, en estadios tempranos, atendidas entre 2007 y diciembre de 2016. Criterios de inclusión: pacientes con límites de edad de 18 y 40 años, nulíparas, con deseo de fertilidad, haber sido tratadas con megestrol, DIU-levonorgestrel o progesterona micronizada durante seis meses. A todas las pacientes se les tomó una biopsia endometrial a los 6 y 12 meses. Se utilizó estadística descriptiva y comparaciones entre mediciones, χ2 o t de Student según la distribución de cada variable. RESULTADOS: Se incluyeron 11 pacientes con cáncer endometrial con edad promedio de 32 ± 2.4 años. La biopsia tomada a los seis meses fue: respuesta completa en 6/11, respuesta parcial en 2/11 y persistencia en 2/11; en una paciente no se tomó la biopsia a los seis meses por embarazo, no hubo casos de progresión. A los 12 meses de seguimiento hubo 5 respuestas completas, 2 parciales, 2 persistencias, 1 caso de progresión de la enfermedad y otro que suspendió el tratamiento. Se efectuaron 8 ciclos de FIV en 6 pacientes con tasa de embarazo de 25%. La duración del tratamiento fue de 19.3 ± 8 meses, el seguimiento total fue de 31.6 ± 13 meses. CONCLUSIONES: El tratamiento conservador de la fertilidad con progestinas en pacientes con cáncer endometrial, en etapas tempranas, es factible y seguro. El embarazo debe intentarse inmediatamente después de una respuesta completa.

Abstract OBJECTIVE: To estimate the complete response rate and pregnancy in women with endometrial cancer who have received conservative treatment with progestins. MATERIALS AND METHODS: Cohort, retrolective and transversal study carried out in the National Institute of Perinatology, in women with endometrial cancer in early stages between 2007 and December 2016. Including patients between 18-40 years, nulliparous, with desire for fertility. The progestins used were megestrol, IUD-levonorgestrel and micronized progesterone for six months. Endometrial biopsy was performed at 6 and 12 months; The result was classified as a complete, partial response, persistence or progression of the disease. Descriptive statistics and comparisons between baseline measurements at six and 12 months are used using student grid and / or t tests according to the distribution of each variable. It is a statistical program SPSS version 23 for Windows (Chicago, USA). RESULTS: 11 women with endometrial cancer were included. The average age of the women was 32 ± 2.4 years. Morbidity associated with hypothyroidism and type 2 diabetes mellitus. Six-month biopsy was: complete response 6/11 partial response 2/11 and persistence 2/11, in one patient the biopsy was not performed at 6 months by pregnancy, there were no cases of progression. At 12 months of follow-up, there were 5 complete responses, 2 partial responses, 2 persistences, 1 case of disease progression and one case that discontinued treatment. Eight cycles of IVF were performed in 6 patients with a pregnancy rate of 25%, the duration of treatment was 19.3 ± 8 months, the total follow-up was 31.6 ± 13 months. CONCLUSIONS: Conservative fertility therapy with progestins in women younger than 40 years old with early-stage endometrial cancer is feasible and secure in our institution. Pregnancy must be sought immediately after a full response to the cancer treatment. Our findings are similar to the ones found in our systematic review of the international bibliography.

Fertility-preserving treatment for early stage endometrial cancer / 中国实用妇科与产科杂志

The fertility preservation treatment has become one of the main issues with the increasing incidence of endometrial cancer.Strict selection of the young endometrial cancer patients who are eligible for fertility preservation treatment and individualizedtreatment plan are fundamental for improving treatmenteffect while decreasing the risk of treatment-relatedcomplications and treatment failure.This article willdiscuss the evaluation and treatment choice for fertilitypreservation in young endometrial cancer patients.

Study on relationship between interaction of estrogen, progesterone and relaxin with stress urinary incontinence during pregnancy / 重庆医学

Objective To study the relationship between the expression levels of estrogen,progesterone,relaxin(RLX) and expression levels of vaginal wall hormone receptors in late pregnancy with stress urinary incontinence(SUI) during pregnancy.Methods Ninety-three healthy pregnant women were selected from July 2014 to November 2015,including 47 cases in the SUI group and 46 cases in the non-SUI group.The blood sample was collected at 37-40 weeks gestation.The levels of serum E2,E3,P and RLX were respectively detected by using the chemiluminescence immunoassay and enzyme linked immunosorbent assay(ELISA).The full thickness tissues of posterior vaginal wall were obtained at delivery in 42 cases of the SUI group and 44 cases of the non-SUI group,and the expressions of ER,PR and LGR7 in pelvic floor tissues were detected by immunohistochemical staining.Results There was no statistically significant difference in serum E2,E3 and P levels between the SUI group and the non-SUI group(P＞0.05);the serum RLX level of the SUI group was significantly higher than that of the non-SUI group(P＜0.05).The positive expression intensity of ER in pelvic floor tissue of the SUI group was lower than that of the non-SUI group(P＜0.05),the positive expression intensity of PR and LGR7 in the SUI group was higher than that in the non-SUI group(P＜0.05).The serum RLX level and expression of LGR7 in pelvic floor tissues of pregnant women had no correlation with E2,E3 and P(P＞0.05).The LGR7 level in pelvic floor tissues had no correlation with ER,and was positively correlated with PR.Conclusion In late pregnancy,the biological activity of estrogen,progesterone and RLX on pelvic floor support tissues is mediated by their receptors expression levels,the progesterone receptor may have a positive regulation effect on LGR7,which is closely related to the occurrence of SUI in pregnancy.

Would male hormonal contraceptives affect cardiovascular risk? / 亚洲男科学杂志(英文版)

The aim of hormonal male contraception is to prevent unintended pregnancies by suppressing spermatogenesis. Hormonal male contraception is based on the principle that exogenous administration of androgens and other hormones such as progestins suppress circulating gonadotropin concentrations, decreasing testicular Leydig cell and Sertoli cell activity and spermatogenesis. In order to achieve more complete suppression of circulating gonadotropins and spermatogenesis, a progestin has been added testosterone to the most recent efficacy trials of hormonal male contraceptives. This review focusses on the potential effects of male hormonal contraceptives on cardiovascular risk factors, lipids and body composition, mainly in the target group of younger to middle-aged men. Present data suggest that hormonal male contraception can be reasonably regarded as safe in terms of cardiovascular risk. However, as all trials have been relatively short (< 3 years), a final statement regarding the cardiovascular safety of hormonal male contraception, especially in long-term use, cannot be made. Older men with at high risk of cardiovascular event might not be good candidates for hormonal male contraception. The potential adverse effects of hormonal contraceptives on cardiovascular risk appear to depend greatly on the choice of the progestin in regimens for hormonal male contraceptives. In the development of prospective hormonal male contraception, data on longer-term cardiovascular safety will be essential.

Long-Acting Reversible Contraception / Contracepção reversível de longa ação

Abstract Unwanted pregnancy is a major public health problem both in developed and developing countries. Although the reduction in the rates of these pregnancies requires multifactorial approaches, increasing access to long-acting contraceptive methods can contribute significantly to change this scenario. In Brazil, gynecologists and obstetricians play a key role in contraceptive counseling, being decisive in the choice of long-acting reversible methods, characterized by intrauterine devices (IUDs) and the contraceptive implant. The vast scope due to the reduced number of situations to indicate long-acting methods should be emphasized in routine contraceptive counseling. On the other hand, gynecologists and obstetricians should adapt the techniques of insertion of long-acting methods, and engage in facilitating conditions to access these contraceptives through public and private health systems in Brazil. This study is part of a project called Diretrizes e Recomendações FEBRASGO (Guidelines and Recommendations of the FEBRASGO - Brazilian Federation of Gynecology and Obstetrics Associations from the Portuguese acronym). It aims to review the main characteristics of long-acting contraceptives and critically consider the current situation and future prospects to improve access to these methods, proposing practical recommendations of interest in the routine of gynecologists and obstetricians.

Resumo A gravidez não planejada representa importante problema de saúde pública tanto em países desenvolvidos quanto naqueles em desenvolvimento. Embora a redução das taxas dessas gestações requeira abordagens multifatoriais, o aumento no acesso aos métodos contraceptivos de longa ação pode contribuir de forma expressiva na mudança desse cenário. No Brasil, os ginecologistas e obstetras têm papel fundamental no aconselhamento contraceptivo, sendo decisivos na escolha dos métodos reversíveis de longa ação, caracterizados pelos dispositivos intrauterinos (DIUs) e pelo implante anticoncepcional. A grande abrangência decorrente do pequeno número de situações que contraindicam os métodos de longa ação deve ser enfatizada no aconselhamento contraceptivo de rotina. Por outro lado, os ginecologistas e obstetras devem se adaptar às técnicas de inserção dos métodos de longa ação, bem como se engajar na facilitação de condições para o acesso a esses contraceptivos por meio do sistema de saúde pública e privada no Brasil. Este estudo, parte do projeto denominado "Diretrizes e Recomendações FEBRASGO", tem por objetivo revisar as principais características dos contraceptivos de longa ação, além de considerar de forma crítica o panorama atual e as perspectivas futuras, visando melhorar o acesso a esses métodos, com recomendações práticas de interesse na rotina do ginecologista e obstetra.

Characteristics and prognosis of estrogen receptor negative breast cancer / 国际外科学杂志

Objective To explore the clinical and pathological characterizations of single progesterone receptor positive breast cancer,and identify the prognostic factors.Methods Obtained from SEER database,the author selected female patients diagnosed with invasive ductal breast cancer between January 1,2010,and December 31,2013.Seven hundred and seventy-five cases were single progesterone receptor positive breast cancer and 12 075 cases were triple negative breast cancers.Patient characteristics were compared using a Chi-square test or Fisher's exact test as appropriate.The Kaplan-Meier method was used to construct survival curves.The multivariate COX regression models were built to assess the independent association of all the variables.Results There was no significant difference between the two groups in terms of race (P =0.711),tumor location (P =0.325),marital status (P =0.255),Grade (P =0.773),tumor size (P =0.949),lymph node status (P =0.821),stage (P =0.567) or radiation treatment (P =0.434).Compared with triple negative breast cancer,patients with single progesterone receptor positive breast cancer tended to be younger(P =0.001),however no significant difference was found in breast cancer-specific survival(P =0.481)between the two groups.Larger tumor size [HR =2.777 (95％ CI:1.295-5.955),P =0.009],and lymph node invasion [HR =3.669 (95％ CI:1.881-7.154),P ＜ 0.001] could significantly increase the risk of dying from cancer in single progesterone receptor positive breast cancer patients.Conclusions Single progesterone receptor positive breast cancer presented with an early onset of disease,and experienced similar cancer-specific survival as triple negative breast cancer.Tumor size and lymph node status were independent prognostic factors.

Progesterone treatment for early miscarriage / 中华全科医师杂志

Spontaneous miscarriage is the most common complication of the first trimester,among which 90% are early miscarriage that occurs prior to the 12th week of the gestation.Low progesterone level may be the main cause of the early miscarriage.This article discusses the incidence,pathogenesis,progesterone treatment,and prediction marker of early miscarriage to provide clues for the clinical work.

The change of female progesterone level and blood calcium concentration in perimenopausal women with benign paroxysmal positional vertigo / 中华耳鼻咽喉头颈外科杂志

Objective@#The estrogen level and blood calcium concentration changes were studied on menopausal women with benign paroxysmal positional vertigo (BPPV).@*Methods@#Between January 2015 and January 2016, 70 menopause women with BPPV in outpatient clinics of Department of Otorhinolaryngology, Inner Mongolia Medical University Affiliated Hospital were included in this study as research group, while 30 menopause healthy women who came to hospital for check-up were included as control group. Serum levels of estradiol (E2), follicle stimulating hormone (FSH), luteinizing hormone (LH), progesterone (PRO), testosterone (T), serum prolactin (PRL) and the calcium concentration were analysed and comparied between research group and control group. SPSS17.0 statistical software was used to analyze the data. χ2 test was used to compare the percentage of decreased serum level of sex hormone, and t test was used to compare the serum level of sex hormone and calcium concentration of two groups.@*Results@#In research group, sex hormone decreased proportion of E2 (91%) and PRO (67%) were obviously higher than those in control group (χ2 value was 8.13, 10.28, respectively, all P<0.05). The E2 and PRO in research group were significantly lower than those in control group ((33.18±31.45) pmol/L vs (64.92 ±31.52) pmol/L, (0.64±0.48) nmol/L vs (1.02±0.60) nmol/L, t value was 6.238, 8.566, respectively, all P<0.05). There was no statistically significant difference of the level of LH, PRL, T, FSH and blood calcium concentration in research group compared with control group ((29.81±13.13) U/L vs (27.21±10.19) U/L, (0.49±0.20) nmol/L vs (0.49±0.15) nmol/L, (0.56±0.42) nmol/L vs (0.73±0.62) nmol/L, (64.25±31.44) U/L vs (60.38±29.97) U/L, (2.28±0.17) mmol/L vs (2.32±0.21) mmol/L, t value was 13.427, 14.876, 7.505, 12.090, 7.532, respectively, all P>0.05).@*Conclusion@#The level of E2 and PRO decrease obviously in postmenopausal women with BPPV, which can cause the inner ear microcirculation disorder , may be one of the risk factors of BPPV.

Research Progress of Fertility-sparing Management in Young Endometrial Cancer Patients Based on ESGO Recommendations / 中国微创外科杂志

[Summary] A more conservative approach for endometrial cancer ( EC ) is desirable in women who have requirement to preserve fertility, without compromising their survival .In this article, we tried to formulate clinical recommendations of preserving fertility based on suggestions of European Society of Gynaecological Oncology ( ESGO) in 2015 and relevant research progress .

Therapeutic options for management of endometrial hyperplasia / 부인종양

Endometrial hyperplasia (EH) comprises a spectrum of changes in the endometrium ranging from a slightly disordered pattern that exaggerates the alterations seen in the late proliferative phase of the menstrual cycle to irregular, hyperchromatic lesions that are similar to endometrioid adenocarcinoma. Generally, EH is caused by continuous exposure of estrogen unopposed by progesterone, polycystic ovary syndrome, tamoxifen, or hormone replacement therapy. Since it can progress, or often occur coincidentally with endometrial carcinoma, EH is of clinical importance, and the reversion of hyperplasia to normal endometrium represents the key conservative treatment for prevention of the development of adenocarcinoma. Presently, cyclic progestin or hysterectomy constitutes the major treatment option for EH without or with atypia, respectively. However, clinical trials of hormonal therapies and definitive standard treatments remain to be established for the management of EH. Moreover, therapeutic options for EH patients who wish to preserve fertility are challenging and require nonsurgical management. Therefore, future studies should focus on evaluation of new treatment strategies and novel compounds that could simultaneously target pathways involved in the pathogenesis of estradiol-induced EH. Novel therapeutic agents precisely targeting the inhibition of estrogen receptor, growth factor receptors, and signal transduction pathways are likely to constitute an optimal approach for treatment of EH.

Fertility-preserving treatment in complex atypical hyperplasia and early endometrial cancer in young women with oral progestin: Is it effective?

OBJECTIVE: The aim of this study is to assess the effectiveness of oral progestin treatment in women diagnosed with complex atypical hyperplasia (CAH) or grade 1 endometrial cancer (G1EC), who desire to preserve their fertility, as alternative treatment to a hysterectomy. METHODS: We reviewed the medical records of women younger than 45 years old that had been diagnosed with CAH or G1EC, who expressed a desire to preserve their fertility using alternative treatment at our institution. Women without evidence of myometrial invasion on pelvic magnetic resonance imaging scans were included. The study period was between 2004 and 2014. Endometrial biopsies were taken at follow-up appointments. RESULTS: We identified 31 young women with CAH or G1EC. The median age was 33 years old (range, 20 to 41), and the median period of time undertaking the treatment was 5 months (range, 1 to 12). Twenty-three patients (74.2%) achieved complete remission (CR; median time to CR was 3 months; range, 1 to 22), 16 patients (88.9%) with CAH and 7 (53.8%) with G1EC achieved CR. 6 patients (26.1%) who had achieved CR, had recurrence of the disease (median time from CR to recurrence was 12.5 months; range, 4 to 18). Eight patients (25.8%) finally underwent a hysterectomy. CONCLUSION: Oral progestin therapy is an alternative treatment for women with CAH or G1EC who desire fertility preservation. However, more prospective studies are needed for standard progestin regimen. Also, there still remains a risk of disease progression and recurrence. Therefore, close follow-up is important during treatment and after CR. In addition, a hysterectomy is recommended as a definitive treatment after completion of childbearing.