A new screening of preterm birth in gestation with short cervix after pessary plus progesterone.

Objective: This study aims to create a new screening for preterm birth < 34 weeks after gestation with a cervical length (CL) ≤ 30 mm, based on clinical, demographic, and sonographic characteristics. Methods: This is a post hoc analysis of a randomized clinical trial (RCT), which included pregnancies, in middle-gestation, screened with transvaginal ultrasound. After observing inclusion criteria, the patient was invited to compare pessary plus progesterone (PP) versus progesterone only (P) (1:1). The objective was to determine which variables were associated with severe preterm birth using logistic regression (LR). The area under the curve (AUC), sensitivity, specificity, and positive predictive value (PPV) and negative predictive value (NPV) were calculated for both groups after applying LR, with a false positive rate (FPR) set at 10%. Results: The RCT included 936 patients, 475 in PP and 461 in P. The LR selected: ethnics white, absence of previous curettage, previous preterm birth, singleton gestation, precocious identification of short cervix, CL < 14.7 mm, CL in curve > 21.0 mm. The AUC (CI95%), sensitivity, specificity, PPV, and PNV, with 10% of FPR, were respectively 0.978 (0.961-0.995), 83.4%, 98.1%, 83.4% and 98.1% for PP < 34 weeks; and 0.765 (0.665-0.864), 38.7%, 92.1%, 26.1% and 95.4%, for P < 28 weeks. Conclusion: Logistic regression can be effective to screen preterm birth < 34 weeks in patients in the PP Group and all pregnancies with CL ≤ 30 mm.

Preparation of a sustainable magnetic sorbent for the extraction and preconcentration of progestogens in natural water samples.

A film composed of agarose and graphene (G) and magnetic nanoparticles (G-MNPs) is proposed as a sorbent for the extraction and determination of medroxyprogesterone (MED), levonorgestrel (LEV), norethisterone (NOR) and progesterone (PRO) in natural water samples. Both the preparation of the film and the extraction procedure were optimized. The optimal extraction parameters were as follows: isopropyl alcohol as activation solvent, sample pH value of 3.0, extraction time of 30 min, 1.00 mL of acetonitrile as eluent, elution time of 5 min and sample volume of 100.00 mL. HPLC with photodiode array detector was used for the separation and determination. The method presented a linear range between 2.50 and 75.0 µg L-1 for all analytes, and the LODs were between 1.40 and 1.80 µg L-1. The method was applied to natural water samples, obtaining satisfactory recovery values (75-111 %). In conclusion, for the immobilization of the G-MNPs, agarose was used, which is a non-toxic, renewable and biodegradable material. The G-MNPs-agarose film was reused up to 70 times, without losing its extraction capacity significantly and presenting excellent sorbent properties, which allow the extraction and preconcentration of the progestogens under study.

Real-world utilization pattern of dydrogesterone in 7287 Indian women with obstetric and gynecological conditions: data from multicentric, retrospective study.

Objective: Despite the literature on dydrogesterone, studies on dydrogesterone utilization patterns are largely lacking in Indian patients. Methods: This was a multi-center, retrospective, observational, cross-sectional, and descriptive study across 817 centers in India. Data of patients who received dydrogesterone in past and provided consent for future use of their medical record for research purpose was were retrieved and analyzed. Results: Data of 7287 subjects (aged 29.55±4.84 years) was analyzed. Threatened abortion was the most common indication for which the subjects received dydrogesterone (46.9%) followed by recurrent pregnancy loss. Polycystic ovary syndrome (PCOS), thyroid disorders and anemia were the most common comorbid conditions and prior pregnancy loss, advanced maternal age and obesity were the most common risk factors seen in subjects who received dydrogesterone. Total 27.5% of subjects received a loading dose of dydrogesterone, and majority (64%) received 40 mg as loading dose. 10 mg dose was used as maintenance or regular dose in 81.4% of the subjects. Twice daily (BID) was the most common dosing frequency (66.6%). The most common concomitant medications being taken by the subjects on dydrogesterone included folic acid (45.1%), iron supplements (30.3%) and calcium and vitamin D3 supplements (25.5%). Another progesterone preparation (oral, injection, vaginal, tubal) other than dydrogesterone was used concurrently in 7.8% of subjects. Conclusion: The study helped to identify the patient population that is benefitted by dydrogesterone and the preferred indications, risk factors, comorbid conditions and concomitant medication used in this patient population at real-life scenario.

Effect of hormone therapy on blood pressure and hypertension in postmenopausal women: a systematic review and meta-analysis.

IMPORTANCE: Menopausal hormone therapy (HT) includes a wide variety of hormonal compounds, and its effect on blood pressure is still uncertain. OBJECTIVE: The aim of this study was to assess evidence regarding the effect of HT on blood pressure in postmenopausal women and its association with arterial hypertension. EVIDENCE REVIEW: This systematic review and meta-analysis included randomized clinical trials and prospective observational studies. Systolic blood pressure (SBP), diastolic blood pressure (DBP), and the incidence of hypertension were assessed. All stages were independently performed by two reviewers. For blood pressure outcome, standardized mean differences (SMD) and 95% confidence intervals (95% CI) were calculated as effect measures. Heterogeneity was assessed using the I2 statistic. The results are presented based on the HT type. The incidence of hypertension was compared using descriptive analyses. FINDINGS: Eleven studies were included with 81,041 women evaluated, of which 29,812 used HT. The meta-analysis, conducted with 8 studies and 1,718 women, showed an increase in SBP with the use of oral conjugated equine estrogens plus progestogen (SMD = 0.60 mm Hg, 95% CI = 0.19 to 1.01). However, oral or transdermal use of estradiol plus progestogen (SMD = -2.00 mm Hg, 95% CI = -7.26 to 3.27), estradiol alone, and tibolone did not show any significant effect. No significant effect on DBP was observed for any formulation. Women who used oral estrogen plus progestogen had a higher risk of incident hypertension than those who never used it. CONCLUSIONS AND RELEVANCE: The effect of HT on blood pressure is influenced by the formulation used, especially the type of estrogen. The combined formulations of conjugated equine estrogens plus progestogen increased SBP and the risk of hypertension, which was not observed among estradiol plus progestogen, estradiol alone, and tibolone users.

Concurrent progestogen and cerclage to reduce preterm birth: a multicenter international retrospective cohort.

BACKGROUND: Both progestogens and cerclage are individually effective in preterm birth prevention in high risk pregnancies. However, national and international guidelines cite a lack of data available to comment on the potential benefit of concurrent progestogen therapy after cerclage has been placed. Studies to date have been small with mixed results regarding benefit of concurrent progestogen with cerclage leaving uncertainty regarding best clinical practice. OBJECTIVE: This study aimed to evaluate whether cerclage with progestogen therapy was superior to cerclage alone in the prevention of spontaneous preterm birth in singleton pregnancies. METHODS: This is an international retrospective cohort study of singleton pregnancies, without major anomaly or aneuploidy, and with cerclage placed at 10 different institutions in the United States and Colombia from June 2016 to June 2020. Exclusion criteria were lack of documentation regarding whether progestogen was prescribed, unavailable delivery outcome, and pregnancy termination (spontaneous or induced) before 16 weeks' gestation. The exposure of interest was progestogen use with cerclage placement, which included those who continued to use progestogen or who started progestogen after cerclage. The comparison group consisted of those without progestogen use after cerclage placement, which included those who had no progestogen use during the entire pregnancy or who initiated progestogen and then stopped it after cerclage placement. Progestogen type, cerclage indication, maternal baseline characteristics, and maternal/neonatal outcomes were collected. The primary outcome was spontaneous preterm birth at <37 weeks. The secondary outcomes were spontaneous preterm birth at <34 weeks, gestational age at delivery, and a composite neonatal outcome including ≥1 of the following: perinatal mortality, confirmed sepsis, grade III or IV intraventricular hemorrhage, retinopathy of prematurity, respiratory distress syndrome, and bronchopulmonary dysplasia. There were planned subgroup analyses by cerclage indication, progestogen type (vaginal progesterone vs 17-hydroxyprogesterone caproate), preterm birth history, and site. Continuous variables were compared in adjusted analyses with analysis of covariance, and categorical variables were compared with multivariable logistic regression, adjusting for potential confounders with adjusted odds ratio. A Cox regression survival curve was generated to compare latency to spontaneous delivery, censored after 37 weeks. RESULTS: During the study period, a total of 699 singletons met the inclusion criteria: 561 in the progestogen with cerclage group and 138 with cerclage alone. Baseline characteristics were similar, except the higher likelihood of previous spontaneous preterm birth in the progestogen group (61% vs 41%; P<.001). Within the progestogen group, 52% were on 17-hydroxyprogesterone caproate weekly, 44% on vaginal progesterone daily, and 3% on oral progesterone daily. Progestogen with cerclage was associated with a significantly lower frequency of spontaneous preterm birth <37 weeks (31% vs 39%; adjusted odds ratio, 0.59 [0.39-0.89]; P=.01) and <34 weeks (19% vs 27%; adjusted odds ratio, 0.55 [0.35-0.87]; P=.01), increased latency to spontaneous delivery (hazard ratio for spontaneous preterm birth <37 weeks, 0.66 [0.49-0.90]; P=.009), and lower frequency of perinatal death (7% vs 16%; adjusted odds ratio, 0.37 [0.20-0.67]; P=.001). In planned subgroup analyses, association with reduced odds of preterm birth <37 weeks persisted in those on vaginal progesterone, those without a previous preterm birth, those with ultrasound- or examination-indicated cerclage, those who started progestogen therapy before cerclage, and in sites restricted to the United States. CONCLUSION: Use of progestogen with cerclage was associated with reduced rates of spontaneous preterm birth and early spontaneous preterm birth compared with cerclage alone. Although this study was not sufficiently powered for subgroup analysis, the strength of evidence for benefit appeared greatest for those with ultrasound- or examination-indicated cerclage, and with vaginal progesterone. El resumen está disponible en Español al final del artículo.

Hemolacria or bloody tears in presumed lacrimal endometriosis: a case report / Hemolacria o lágrimas hemáticas en sospecha de endometriosis lacrimal: reporte de un caso

Background: Hemolacria or the presence of blood in tears is a rare condition, and there are only a few cases reported in the literature. Hemolacria is associated with multiple underlying diseases, including vicarious menstruation due to extragenital endometriosis. Case report: We present a 26-year-old woman with hemolacria and abdominal pain related to her menstrual cycle. The patient was diagnosed with bilateral ovarian endometriomas. After ruling out other possible causes of hemolacria, a progestin-only treatment was applied, with improvement of the abdominal pain and complete remission of hemolacria. Conclusions: When faced with hemolacria, a thorough anamnesis and physical examination must be performed, sometimes involving more than one specialist to reach a diagnosis. Considering hemolacria is a sign of a subjacent pathology, its treatment should be specific one for the disease in each case.

Antecedentes: La hemolacria o presencia de sangre en las lágrimas es una afección poco frecuente y sólo hay unos pocos casos descritos en la literatura. La hemolacria se asocia a múltiples enfermedades subyacentes, incluida la menstruación vicaria debida a endometriosis extragenital. Caso clínico: Presentamos a una mujer de 26 años con hemolacria y dolor abdominal relacionado con su ciclo menstrual. La paciente fue diagnosticada de endometriomas ováricos bilaterales. Tras descartar otras posibles causas de hemolacria, se aplicó un tratamiento sólo con progestágenos, con mejoría del dolor abdominal y remisión completa de la hemolacria. Conclusiones: Ante una hemolacria se debe realizar una anamnesis y exploración física minuciosa, en la que a veces interviene más de un especialista para llegar al diagnóstico. Teniendo en cuenta que la hemolacria es signo de una patología subyacente, su tratamiento debe ser el específico para la enfermedad en cada caso.

Progestogens for prevention of luteinising hormone (LH) surge in women undergoing controlled ovarian hyperstimulation as part of an assisted reproductive technology (ART) cycle.

BACKGROUND: Currently, gonadotrophin releasing hormone (GnRH) analogues are used to prevent premature ovulation in ART cycles. However, their costs remain high, the route of administration is invasive and has some adverse effects. Oral progestogens could be cheaper and effective to prevent a premature LH surge. OBJECTIVES: To evaluate the effectiveness and safety of using progestogens to avoid spontaneous ovulation in women undergoing controlled ovarian hyperstimulation (COH). SEARCH METHODS: We searched the Cochrane Gynaecology and Fertility Group trials register, CENTRAL, MEDLINE, Embase and PsycINFO in Dec 2021. We contacted study authors and experts to identify additional studies. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that included progestogens for ovulation inhibition in women undergoing controlled ovarian hyperstimulation (COH). DATA COLLECTION AND ANALYSIS: We used standard methodological procedures recommended by Cochrane, including the risk of bias (RoB) assessment. The primary review outcomes were live birth rate (LBR) and oocyte pick-up cancellation rate (OPCR). Secondary outcomes were clinical pregnancy rate (CPR), cumulative pregnancy, miscarriage rate (MR), multiple pregnancies, LH surge, total and MII oocytes, days of stimulation, dose of gonadotropins, and moderate/severe ovarian hyperstimulation syndrome (OHSS) rate. The primary analyses were restricted to studies at overall low and some concerns RoB, and sensitivity analysis included all studies. We used the GRADE approach to assess the certainty of evidence. MAIN RESULTS: We included 14 RCTs (2643 subfertile women undergoing ART, 47 women used oocyte freezing for fertility preservation and 534 oocyte donors). Progestogens versus GnRH antagonists We are very uncertain of the effect of medroxyprogesterone acetate (MPA) 10 mg compared with cetrorelix on the LBR in poor responders (odds ratio (OR) 1.25, 95% confidence interval (CI) 0.73 to 2.13, one RCT, N = 340, very-low-certainty evidence), suggesting that if the chance of live birth following GnRH antagonists is assumed to be 18%, the chance following MPA would be 14% to 32%. There may be little or no difference in OPCR between progestogens and GnRH antagonists, but due to wide Cs (CIs), we are uncertain (OR 0.92, 95%CI 0.42 to 2.01, 3 RCTs, N = 648, I² = 0%, low-certainty evidence), changing the chance of OPCR from 4% with progestogens to 2% to 8%. Given the imprecision found, no conclusions can be retrieved on CPR and MR. Low-quality evidence suggested that using micronised progesterone in normo-responders may increase by 2 to 6 the MII oocytes in comparison to GnRH antagonists. There may be little or no differences in gonadotropin doses. Progestogens versus GnRH agonists Results were uncertain for all outcomes comparing progestogens with GnRH agonists. One progestogen versus another progestogen The analyses comparing one progestogen versus another progestogen for LBR did not meet our criteria for primary analyses. The OPCR was probably lower in the MPA 10 mg in comparison to MPA 4 mg (OR 2.27, 95%CI 0.90 to 5.74, one RCT, N = 300, moderate-certainty evidence), and MPA 4 mg may be lower than micronised progesterone 100 mg, but due to wide CI, we are uncertain of the effect (OR 0.81, 95%CI 0.43 to 1.53, one RCT, N = 300, low-certainty evidence), changing the chance of OPCR from 5% with MPA 4 mg to 5% to22%, and from 17% with micronised progesterone 100 mg to 8% to 24%. When comparing dydrogesterone 20 mg to MPA, the OPCR is probably lower in the dydrogesterone group in comparison to MPA 10 mg (OR 1.49, 95%CI 0.80 to 2.80, one RCT, N = 520, moderate-certainty evidence), and it may be lower in dydrogesterone group in comparison to MPA 4 mg but due to wide confidence interval, we are uncertain of the effect (OR 1.19, 95%CI 0.61 to 2.34, one RCT, N = 300, low-certainty evidence), changing the chance of OPCR from 7% with dydrogesterone 20 to 6-17%, and in MPA 4 mg from 12% to 8% to 24%. When comparing dydrogesterone 20 mg to micronised progesterone 100 mg, the OPCR is probably lower in the dydrogesterone group (OR 1.54, 95%CI 0.94 to 2.52, two RCTs, N=550, I² = 0%, moderate-certainty evidence), changing OPCR from 11% with dydrogesterone to 10% to 24%. We are very uncertain of the effect in normo-responders of micronised progesterone 100 mg compared with micronised progesterone 200 mg on the OPCR (OR 0.35, 95%CI 0.09 to 1.37, one RCT, N = 150, very-low-certainty evidence). There is probably little or no difference in CPR and MR between MPA 10 mg and dydrogesterone 20 mg. There may be little or no differences in MII oocytes and gonadotropins doses. No cases of moderate/severe OHSS were reported in most of the groups in any of the comparisons. AUTHORS' CONCLUSIONS: Little or no differences in LBR may exist when comparing MPA 4 mg with GnRH agonists in normo-responders. OPCR may be slightly increased in the MPA 4 mg group, but MPA 4 mg reduces the doses of gonadotropins in comparison to GnRH agonists. Little or no differences in OPCR may exist between progestogens and GnRH antagonists in normo-responders and donors. However, micronised progesterone could improve by 2 to 6 MII oocytes. When comparing one progestogen to another, dydrogesterone suggested slightly lower OPCR than MPA and micronised progesterone, and MPA suggested slightly lower OPCR than the micronised progesterone 100 mg. Finally, MPA 10 mg suggests a lower OPCR than MPA 4 mg. There is uncertainty regarding the rest of the outcomes due to imprecision and no solid conclusions can be drawn.

Quantitative Analysis of Cellular Morphology During In Vitro Decidualization.

Decidualization is a differentiation process involving shape reorganization from a fibroblast to an epithelioid-like appearance characteristic of endometrial stromal cells. For the study of in vitro decidualization, one needs to check that the cells have undergone this process effectively. Verification is usually done by analyzing the expression of decidual markers, but changes in morphology are a more comprehensive feature. However, morphological specificities (i.e., flatness) of endometrial cells prevent the use of existing automated tools. A simple and accurate methodology was developed to quantify the phenotypic changes that occur in an in vitro decidualization system. This approach analyzes cell circularity directly from light microscopy images to follow the effects of progesterone or progestin R5020 in combination with estradiol (E2) and cAMP in inducing the decidualization of human endometrial cells. A statistical model to detect the differences in the kinetics of decidualization of the two hormonal stimuli before all the cell population acquire the decidual phenotype was implemented. It was found that statistical differences in morphology between decidualized and control cells could be detected 2 days after the treatments. Here we detail the model applied, scripts, and input files in order to provide a useful, practical, and low-cost tool to evaluate morphological aspects of endometrial stromal differentiation. This method allows the verification of the effectiveness of the decidualization process of the stromal endometrial cells without having to use cell replicates, as other methods such as immunofluorescence and RT-qPCR assays require. Consequently, this approach can follow the kinetics of a living single replicate throughout the experiment. © 2023 Wiley Periodicals LLC. Basic Protocol 1: Cell circularity quantification of human stromal endometrial cells using ImageJ Basic Protocol 2: Statistical analysis of cell circularity of human stromal endometrial cells.

Tolerability of endometriosis medical treatment: a comparison between combined hormonal contraceptives and progestins.

Endometriosis is a chronic inflammatory disease that occurs in women of reproductive age. Much of the treatment involves hormone therapy that suppresses the proliferation of endometriosis lesions.Objective To compare discontinuation rates of pharmacological treatment with estrogen-progestins and progestins medications. The secondary objective is to evaluate the main side effects of these drugs in patients with endometriosis.Methods This retrospective study analyzed data from 330 patients who attended the Hospital of the State Public Servant of São Paulo from August 1999 to September 2020 and received pharmacological treatment for endometriosis. The data were obtained by review of the files of medical appointments with specialized staff.Results The median treatment time was 18 months, ranging from 1 to 168 months, and 177 patients interrupted the proposed treatment. The combined contraceptives with estrogens and progestins were significantly linked to treatment interruption, with a relative risk of 1,99 (p = 0,005). The most important side effects that resulted in treatment interruption were pain persistence (p = 0,043), weight gain (p = 0,017) and spotting (p < 0,001).

Hormone therapy for sexual function in perimenopausal and postmenopausal women.

BACKGROUND: The perimenopausal and postmenopausal periods are associated with many symptoms, including sexual complaints. This review is an update of a review first published in 2013. OBJECTIVES: We aimed to assess the effect of hormone therapy on sexual function in perimenopausal and postmenopausal women. SEARCH METHODS: On 19 December 2022 we searched the Gynaecology and Fertility Group Specialised Register, CENTRAL, MEDLINE, Embase, PsycINFO, CINAHL, LILACS, ISI Web of Science, two trials registries, and OpenGrey, together with reference checking and contact with experts in the field for any additional studies. SELECTION CRITERIA: We included randomized controlled trials that compared hormone therapy to either placebo or no intervention (control) using any validated assessment tool to evaluate sexual function. We considered hormone therapy: estrogen alone; estrogen in combination with progestogens; synthetic steroids, for example, tibolone; selective estrogen receptor modulators (SERMs), for example, raloxifene, bazedoxifene; and SERMs in combination with estrogen. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures recommended by Cochrane. We analyzed data using mean differences (MDs) and standardized mean differences (SMDs). The primary outcome was the sexual function score. Secondary outcomes were the domains of sexual response: desire; arousal; lubrication; orgasm; satisfaction; and pain. We assessed the certainty of the evidence using the GRADE approach. MAIN RESULTS: We included 36 studies (23,299 women; 12,225 intervention group; 11,074 control group), of which 35 evaluated postmenopausal women; only one study evaluated perimenopausal women. The 'symptomatic or early postmenopausal women' subgroup included 10 studies, which included women experiencing menopausal symptoms (symptoms such as hot flushes, night sweats, sleep disturbance, vaginal atrophy, and dyspareunia) or early postmenopausal women (within five years after menopause). The 'unselected postmenopausal women' subgroup included 26 studies, which included women regardless of menopausal symptoms and women whose last menstrual period was more than five years earlier. No study included only women with sexual dysfunction and only seven studies evaluated sexual function as a primary outcome. We deemed 20 studies at high risk of bias, two studies at low risk, and the other 14 studies at unclear risk of bias. Nineteen studies received commercial funding. Estrogen alone versus control probably slightly improves the sexual function composite score in symptomatic or early postmenopausal women (SMD 0.50, 95% confidence interval (CI) (0.04 to 0.96; I² = 88%; 3 studies, 699 women; moderate-quality evidence), and probably makes little or no difference to the sexual function composite score in unselected postmenopausal women (SMD 0.64, 95% CI -0.12 to 1.41; I² = 94%; 6 studies, 608 women; moderate-quality evidence). The pooled result suggests that estrogen alone versus placebo or no intervention probably slightly improves sexual function composite score (SMD 0.60, 95% CI 0.16 to 1.04; I² = 92%; 9 studies, 1307 women, moderate-quality evidence). We are uncertain of the effect of estrogen combined with progestogens versus placebo or no intervention on the sexual function composite score in unselected postmenopausal women (MD 0.08 95% CI -1.52 to 1.68; 1 study, 104 women; very low-quality evidence). We are uncertain of the effect of synthetic steroids versus control on the sexual function composite score in symptomatic or early postmenopausal women (SMD 1.32, 95% CI 1.18 to 1.47; 1 study, 883 women; very low-quality evidence) and of their effect in unselected postmenopausal women (SMD 0.46, 95% CI 0.07 to 0.85; 1 study, 105 women; very low-quality evidence). We are uncertain of the effect of SERMs versus control on the sexual function composite score in symptomatic or early postmenopausal women (MD -1.00, 95% CI -2.00 to -0.00; 1 study, 215 women; very low-quality evidence) and of their effect in unselected postmenopausal women (MD 2.24, 95% 1.37 to 3.11 2 studies, 1525 women, I² = 1%, low-quality evidence). We are uncertain of the effect of SERMs combined with estrogen versus control on the sexual function composite score in symptomatic or early postmenopausal women (SMD 0.22, 95% CI 0.00 to 0.43; 1 study, 542 women; very low-quality evidence) and of their effect in unselected postmenopausal women (SMD 2.79, 95% CI 2.41 to 3.18; 1 study, 272 women; very low-quality evidence). The observed heterogeneity in many analyses may be caused by variations in the interventions and doses used, and by different tools used for assessment. AUTHORS' CONCLUSIONS: Hormone therapy treatment with estrogen alone probably slightly improves the sexual function composite score in women with menopausal symptoms or in early postmenopause (within five years of amenorrhoea), and in unselected postmenopausal women, especially in the lubrication, pain, and satisfaction domains. We are uncertain whether estrogen combined with progestogens improves the sexual function composite score in unselected postmenopausal women. Evidence regarding other hormone therapies (synthetic steroids and SERMs) is of very low quality and we are uncertain of their effect on sexual function. The current evidence does not suggest the beneficial effects of synthetic steroids (for example tibolone) or SERMs alone or combined with estrogen on sexual function. More studies that evaluate the effect of estrogen combined with progestogens, synthetic steroids, SERMs, and SERMs combined with estrogen would improve the quality of the evidence for the effect of these treatments on sexual function in perimenopausal and postmenopausal women.

Anticoncepção oral e hipotrofia muscular: existe correlação? / Oral contraception and muscle atrophy: is there a correlation?

As pílulas anticoncepcionais consistem na formulação combinada de um estrogênio e um progestagênio ou em apresentações simples de progestagênio isolado com a finalidade de bloquear a ovulação e alterar as condições do útero e das tubas uterinas, bloqueando parcialmente a foliculogênese e a inibição do pico de gonadotrofinas. Desse modo, no que concerne à temática, diversas publicações na mídia de ampla divulgação afirmam que os anticoncepcionais orais têm papel importante na sarcopenia e na hipotrofia, incluindo perda de força muscular e redução do desempenho físico. Assim, o presente trabalho tem por objetivo avaliar, por meio de pesquisas de artigos, a correlação entre anticoncepcionais hormonais orais e hipotrofia muscular. Foi concluído que os artigos científicos especializados no tema são ainda bastante inconclusivos, sugerindo que há indicações de que usuárias de anticoncepcional oral sejam mais suscetíveis ao dano muscular induzido por exercícios, contudo ainda não há consenso.

Anticonception pills consist of a combined formulation of an estrogen and a progestogen or simple presentations of progestogen alone with the purpose of blocking ovulation and altering the conditions of the uterus and uterine tubes, partially blocking folliculogenesis and inhibiting the gonadotropin peak. Thus, with regard to the subject, several widely publicized media publications claim that oral contraceptives play an important role in sarcopenia and hypotrophy, including loss of muscle strength and reduced physical performance. So, the present work aims to evaluate through article searches the correlation between oral hormonal contraceptives and muscle hypotrophy. It was concluded that scientific articles specialized on the subject are still quite inconclusive, suggesting that there are indications that oral contraceptive users are more susceptible to exercise-induced muscle damage, however there is still no consensus.

Oral combined hormonal contraceptive associated with protection against allodynia in migraine in a cross-sectional study.

INTRODUCTION: For the most part, migraine afflicts young women who often need to use the hormonal contraceptive method. OBJECTIVE: To evaluate the effects of using exogenous estrogen, present in combined hormonal contraceptives (CHC) and progestin-only methods on the prevalence of allodynia in women with migraine. METHODS: Study comprising women diagnosed with migraine, with or without aura, who were not pregnant, breastfeeding, or menopausal. The study was conducted via the digital platform. Data were collected relating to demographics, contraceptive method, anthropometric information, smoking habits, and migraine-related symptoms. The participants then answered the following validated, self-administered questionnaires: Migraine Disability Assessment (MIDAS), Allodynia Symptom Checklist, Generalized Anxiety Disorder (GAD-7), and Beck's Depression Inventory (BDI). In order to determine the variables associated with allodynia, two binary logistic regression models were used. RESULTS: Four hundred eighty-six women took part in the study. Of these, 205 used CHC, 89 used a progestin-only method, and 192 participants did not use any form of hormonal contraception. Allodynia was identified in 411 (84.6%) participants. Allodynia was linked to the presence of aura (OR = 2.76; CI 95% 1.55-4.91; p = 0.001), menstrually related migraine (OR = 2.14; CI 95% 1.28-3.57; p = 0.004), greater disability (MIDAS score 23 vs. 8; p < 0.001), depression (BDI score 14 vs. 10; p < 0.001), and anxiety (GAD-7 score 11 vs. 8; p < 0.001). In adjusted analysis, CHC was associated to protection against allodynia when jointly evaluated all CHC regimens (OR = 0.49 CI 95% 0.26-0.92; p = 0.028), as well as oral CHC individually (OR = 0.48 CI 95% 0.25-0.92; p = 0.027). CONCLUSION: CHC reduced the chances of women with migraine getting allodynia.

Progestogen-Mediated Neuroprotection in Central Nervous System Disorders.

Neuroactive steroids can be synthetic or endogenous molecules produced by neuronal and glial cells and peripheral glands. Examples include estrogens, testosterone, progesterone and its reduced metabolites such as 5α-dihydro-progesterone and allopregnanolone. Steroids produced by neurons and glia target the nervous system and are called neurosteroids. Progesterone and analog molecules, known as progestogens, have been shown to exhibit neurotrophic, neuroprotective, antioxidant, anti-inflammatory, glial modulatory, promyelinating, and remyelinating effects in several experimental models of neurodegenerative and injury conditions. Pleiotropic mechanisms of progestogens may act synergistically to prevent neuron degeneration, astrocyte and microglial reactivity, reducing morbidity and mortality. The aim of this review is to summarize the significant findings related to the actions of progesterone and other progestogens in experimental models and epidemiological and clinical trials of some of the most prevalent and debilitating chronic neurodegenerative disorders, namely, Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, and multiple sclerosis. We evaluated progestogen alterations under pathological conditions, how pathology modifies their levels, as well as the intracellular mechanisms and glial interactions underlying their neuroprotective effects. Furthermore, an analysis of the potential of natural progestogens and synthetic progestins as neuroprotective and regenerative agents, when administered as hormone replacement therapy in menopause, is also discussed.

The Effects of Hormonal Contraceptives on the Sleep of Women of Reproductive Age.

Research about the effects of hormonal contraceptives on sleep has been performed but is subjected to important levels of methodological heterogeneity. Hormonal contraceptives impact sleep, but the direction of this association is not clear. Most studies describe a negative sleep profile among contraceptive users, including increased sleepiness, insomnia symptoms, decreased sleep efficiency, and a reduced overall sleep quality. Hormonal intrauterine contraceptives are associated with less negative effects. More research on the field, especially randomized controlled trials, is needed to increase the level and certainty of evidence about the effects of hormonal contraceptives on sleep.

Macroscopic changes in the mammary glands of healthy cats after progestogen administration / Alterações macroscópicas nas glândulas mamárias de gatas hígidas após administração de progestágeno

The administration of contraceptives in female cats leads to problems such as pyometra, fetal maceration, mammary hyperplasia, and mammary neoplasms. Among the diseases caused by contraceptives, mammary hyperplasia has only been diagnosed in felines. However, few experimental studies have shown that contraceptive administration can cause feline mammary hyperplasia. This study aimed to evaluate the effects of the administration of a single dose of contraceptives in the mammary glands of healthy cats. Twenty cat owners who had administered contraceptives to female cats were selected. Animals were divided into two groups. Contraceptives were administered to cats in the first group, and saline solution was administered to cats in the other group (control). Before drug administration, all cats were clinically examined. Anamnesis, physical examination, blood count, biochemical tests, and abdominal ultrasonography were performed. Thirty days after the administration of contraceptives, all cats were examined, and the examinations were repeated. At 30 days, no changes were observed in the blood count or ultrasound findings. However, upon physical examination, all cats that received contraceptives showed generalized enlargement of their mammary glands. Cats in the control group were clinically normal. Ninety days after the procedure, the cats underwent an ovariohysterectomy. At that time, all cats were clinically normal and mammary enlargement regressed. It was concluded that a single contraceptive application could cause macroscopic mammary changes suggestive of hyperplasia in ten cats.(AU)

A administração de anticoncepcionais em gatas causa problemas como piometra, maceração fetal, hiperplasia mamária e neoplasias mamárias. Dentre as doenças causadas por anticoncepcionais, a hiperplasia mamária tem sido diagnosticada apenas em felinas. No entanto, poucos estudos experimentais comprovaram que a hiperplasia mamária felina pode ser causada pela administração de anticoncepcionais. O objetivo deste estudo foi avaliar os efeitos da administração de dose única de anticoncepcional nas glândulas mamárias de gatas saudáveis. Foram selecionados 20 tutores de gatos que administrariam contraceptivos em suas gatas. Os animais foram divididos em dois grupos. Anticoncepcionais foram administrados às gatas do primeiro grupo, e solução salina foi administrada às gatas do outro grupo (controle). Antes da administração do fármaco, todas as gatas foram examinadas clinicamente. Foram realizados anamnese, exame físico, hemograma, exames bioquímicos e ultrassonografia abdominal. Trinta dias após a administração dos anticoncepcionais, todas as gatas foram examinadas e os exames repetidos. Aos 30 dias, não foram observadas alterações no hemograma ou ultrassonografia. No entanto, ao exame físico, todas as gatas que receberam anticoncepcionais apresentaram aumento generalizado das glândulas mamárias. As gatas do grupo controle estavam clinicamente normais. Noventa dias após o procedimento, as gatas foram submetidas à ovariohisterectomia. Na ocasião do procedimento cirúrgico, todas as gatas apresentavam-se clinicamente normais, havendo regressão do aumento de volume mamário. Concluiu-se que uma única aplicação de anticoncepcional foi capaz de causar alterações mamárias macroscópicas sugestivas de hiperplasia em dez gatas.(AU)

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.

Exposure to levonorgestrel-based birth control pill in early life and its persistent effects in zebrafish.

The consumption of progestins has increased considerably in recent decades, as has their disposal into the environment. These substances can negatively affect the reproduction, physiology, and behavior of non-target organisms, such as fish. We aimed to evaluate the effects of exposure to environmentally relevant concentrations of levonorgestrel-control birth based (1.3, 13.3, 133, and 1330 ng/L) on the development and behavior of zebrafish (Danio rerio) in terms of mortality, hatching, spontaneous movement, and larval and adult behavioral tests. Exposure caused anxiogenic-like behavior in larvae, which persisted in adults, as demonstrated by the light-dark test. In contrast, it caused anxiolytic-like behavior in the novel tank test. There was a high mortality rate at all tested concentrations and increases in the hormone cortisol at 13.3 ng/L that affected the sex ratio. These changes may lead to an ecological imbalance, emphasizing the risk of early exposure to progestins in the environment.

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

Mitigation of low pregnancy rate in excitable Nellore cows by administration of GnRH or P4.

This research aimed to determine the effect of temperament on reproductive parameters including cortisol and progesterone (P4) in Nellore cows. Additionally, two methods for increasing plasma progesterone (P4) levels in excitable animals to enhance pregnancy rate (P/AI) and reduce pregnancy loss were investigated. In total, 939 cows were subjected to timed artificial insemination (TAI) and divided into three groups: (P4LA; n = 305) 150 mg of injectable long-acting progestogen 7 days after TAI; (GnRH; n = 306), 10 µg of buserelin acetate on day 7 after TAI; control group (CG; n = 328) without hormonal treatment. In 213 cows, randomly chosen from each group, ultrasound evaluations of the preovulatory follicle (Mode B) were performed on the day of insemination and of the corpus luteum (Color Doppler) 7 and 16 days after TAI. Blood samples were obtained from 20% of the 939 animals, randomly chosen from each group, on the day of insemination and after 7 and 16 days to measure cortisol and progesterone, respectively. At the time of insemination, subjective temperament evaluations were performed with the animals being classified as excitable (EXC) or adequate (ADQ). The SAS GLIMMIX procedure was used to compare the pregnancy rate (P/AI) and gestational loss within each temperament for the three experimental groups. Continuous variables were analyzed utilizing SAS PROC MIXED procedure. Cortisol concentration was higher and POF (preovulatory follicle) and CL (corpus luteum) volumes at the time of insemination and 7 days after AI, respectively, were lower in EXC animals than in ADQ. No significant difference was observed between the number of pixels, CL intensity, and plasma concentration of P4, 7 days after TAI. However, 16 days post-insemination, among the animals classified as EXC, higher concentrations of P4 were observed in the GnRH and P4LA groups than in the control. Regarding P4 concentrations, there was a tendency to be lower in animals classified as EXC than in ADQ within the control group (P = 0.06), while rate of blood flow from the CL was lower in EXC animals than in ADQ animals (P = 0.04). Among the ADQ animals, the GnRH and P4LA groups showed a lower CL flow rate than that observed in the control (P = 0.04), 16 days after the TAI. Among EXC animals, a higher pregnancy rate was observed in the GnRH and P4LA groups than in the control group (P = 0.01). In the control group, the pregnancy rate (P/AI) of the ADQ animals was higher than that of the EXC animals (P = 0.05). No statistically significant differences were observed between gestational losses when the treatments or temperaments were compared. In conclusion, the use of GnRH or P4LA, 7 days after insemination, improves pregnancy rates in excitable animals and is a viable alternative to minimize the negative impact of stress and improve reproductive efficiency in beef cattle.