Manejo das irregularidades menstruais secundárias ao uso de contraceptivos ­ análise das recomendações atuais / Management of menstrual irregularities secondary to contraceptive use ­ analysis of current recommendations

As irregularidades menstruais representam uma série de desordens na quantida- de, duração, frequência ou regularidade do sangramento uterino. Entre suas cau- sas destaca-se o sangramento secundário ao uso de anticoncepcionais, uma razão frequente de descontinuidade dos contraceptivos, podendo aumentar as taxas de gestações não planejadas. Boa parte dos contraceptivos pode levar a mudanças no padrão de sangramento uterino, e a abordagem inicial do sangramentos irregula- res inclui a avaliação de outras possíveis causas, o reforço do uso correto da medi- cação, a tranquilização da paciente quanto à benignidade do quadro e à tendência a melhora com a continuidade do uso. Os anti-inflamatórios podem ser usados como estratégia inicial, e, não havendo resposta satisfatória, há alternativas espe- cíficas para cada método. Este trabalho visa identificar as recomendações atuais sobre o manejo do sangramento anormal decorrente de contraceptivos, por meio de revisão narrativa de estudos publicados sobre o tema nos últimos vinte anos.

Abnormal uterine bleeding represents a series of disorders in the amount, du- ration, frequency and or regularity of uterine bleeding. Among its causes, uterine bleeding secondary to the use of contraceptives stands out as a frequent reason for contraceptive discontinuity, which could lead to unplanned pregnancies. Most contraceptives can cause changes in the pattern of uterine bleeding, and the ini- tial approach of the abnormal bleeding includes assessing other possible cau- ses, reinforcing the correct use of medication, and reassuring the patient about the benignity of the condition and the tendency to improve with the continuity of the treatment. Anti-inflammatory drugs can be used as an initial strategy, and, if there is no satisfactory answer, there are specific alternatives for each contracep- tive method. This work aims to identify them current recommendations on the management of abnormal bleeding resulting from contraceptives use, through a narrative review of studies published on the subject in the last twenty years.

Image Analysis of TVCDS in Infertile Patients with Polycystic Ovary Syndrome.

In order to analyze and examine the TVCDS images of infertile patients, this paper conducted an in-depth study based on the symptoms of polycystic ovary syndrome. Through the sample size estimation method, mathematical analysis, and other methods, the image examination of the polycystic ovary in TVCDS was successfully analyzed. 86 cases of infertile patients with PCS were divided into a control group treated with clomiphene alone and an observation group treated with clomiphene combined with TCM periodic therapy, with 43 patients in each group. The therapeutic effects of the two groups were compared and analyzed. Results show that the treatment effective rate and pregnancy success rate of the observation group were 95.35% and 88.37%, respectively, and those of the control group were 83.72% and 76.74%, respectively. The difference between the two groups was statistically significant (P < 0.05). It was understood that the main pathogenesis of polycystic ovary syndrome is the abnormal balance of kidney, qi, and blood meridians. Thus, the balance of kidney-anemone-chong Ren-uprisal is broken and the result is infertility symptoms or irregular menstruation. After a study on TVCDS in infertile patients, it was observed that the levels of progesterone (P) and luteinizing hormone (LH) in patients with irregular menstruation were significantly increased. The increase was higher than that in the control group, with an overall negative rate of 4.00%, compared with 18.00% of the control group, showing a significant difference. It also indicates that TVCDS image examination has a very significant effect on improving menstrual irregularities and reducing the incidence of adverse reactions.

Reliability and toxicity of bevacizumab for neurofibromatosis type 2-related vestibular schwannomas: A systematic review and meta-analysis.

BACKGROUND: The anti-angiogenic agent bevacizumab is currently the only drug used clinically for neurofibromatosis type 2-related vestibular schwannomas (NF2-VS). Though benefits have been demonstrated in several cases, the standardized dosage remains unclear. OBJECTIVE: Our meta-analysis was performed to systematically and comprehensively investigate the reliability and toxicity of bevacizumab in the treatment of NF2-VS, with particular emphasis on the impact of dosage. METHODS: The literature search was conducted for studies providing data on patients treated with bevacizumab for NF2-VS across PubMed, Embase, and Cochrane Library until December 31, 2020. Two reviewers extracted the incidence rate of results independently. Then we calculated and pooled unadjusted incidence rate with 95% CIs for each study. The subgroups analyzed were conducted. RESULTS: Fourteen citations (prospective or retrospective observational cohort studies) were eligible based on data from a total of 247 patients with NF2 and 332 related VSs. The pooled results showed that the radiographic response rate (RRR) was 30% [95% CI (20%-42%)], the hearing response rate (HRR) was 32% [95% CI (21%-45%)]. The incidence of major complications was: hypertension 29% [95% CI (23%-35%)], proteinuria 30% [95% CI (18%-44%)], menstrual disorders 44% [95% CI (16%-73%)], hemorrhage 14% [95% CI (4%-26%)], grade3/4 events 12% [95% CI (4%-22%)]. CONCLUSIONS: Nearly one-third of NF2-VS patients may benefit significantly from bevacizumab due to hearing improvement and tumor reduction. Menstrual disorders were the most common adverse events. The high-dose regimen didn't show better efficacy, but results varied considerably according to age.

Dienogest reduces endometrioma volume and endometriosis-related pain symptoms.

This study aimed to evaluate the efficacy and adverse effects of dienogest for the treatment of endometriomas. Dienogest (2 mg/day) was administered to patients with endometrioma continuously through the 6-month study period. The patients were prospectively examined on the efficacy and side effects at baseline, at third months, and sixth months of the treatment. Twenty-four out of 30 patients were able to complete the study. The mean volume of the endometrioma decreased significantly from 112.63 ± 161.31 cm³ at baseline to 65.47 ± 95.69 cm³ at a 6-month follow-up (-41%) (p = .005). The VAS score for pelvic pain decreased significantly from 7.50 to 3.00 (p < .001) at the sixth months of treatment. The most common side effects were menstrual irregularities. Laboratory parameters did not change during the study. Dienogest considered being effective for 6 months of use in decreasing the size of endometrioma, reducing endometriosis-associated pain with a favourable safety and tolerability profile.Impact statementWhat is already known on this subject? Laparoscopic excisional surgery for endometrioma is currently the most valid approach in the treatment of endometriomas. However, there are concerns about ovarian reserve damage during surgery.What do the results of this study add? Dienogest considered being effective in decreasing the size of endometrioma, reducing endometriosis-associated pain with a favourable safety and tolerability profile. Long-term use of dienogest in younger patients with endometriomas who are yet to give birth may reduce the possibility of surgery by reducing the size of the endometriomas and may preserve ovarian reserve.What are the implications of these findings for clinical practice and/or further research? Dienogest may reduce the incidence of infectious complications such as pelvic abscess after oocyte retrieval and the surgical procedures in infertile patients with endometrioma.

Menstrual disorders associated with sirolimus treatment.

INTRODUCTION: Sirolimus has become a pillar in the treatment of vascular anomalies due to its inhibition of the mammalian target of rapamycin (mTOR). Adverse effects include metabolic and hematologic disorders among others, although menstrual disorders have not been well described. MATERIALS AND METHODS: Retrospective review of patients with vascular anomalies on sirolimus treatment was performed. Patients presenting menstrual alterations were included. MAIN RESULTS: One hundred and thirty-six patients with vascular anomalies on treatment with sirolimus were reviewed, finding seven women out of 74 (9.4%) who presented menstrual alterations attributable to the treatment. These seven patients presented with different vascular malformations and three showed pathogenic variants in phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) in affected tissue. Partial response in six and stability in one patient was obtained after treatment, administered for an average of 27.5 months (6-48). Five patients have completed treatment and two patients continue on after 12 and 15 months, respectively. All patients reported regular menstrual cycles prior to sirolimus treatment. One patient presented with amenorrhea for 4 months after treatment initiation that later spontaneously resolved. The other six patients presented with hypermenorrhea, four of them associating metrorrhagia. Most patients presented with mild menstrual alterations, without needing dose reduction or withdrawal, although one discontinued sirolimus due to hypermenorrhea, metrorrhagia, and hematuria. After sirolimus withdrawal, regular menstrual cycles were restored in five patients. CONCLUSION: Sirolimus treatment can produce menstrual disorders as adverse effects. Although mild and reversible upon dose reduction or cessation of treatment, patients and physicians should be aware on this potential side effect.

Free-of-charge long-acting reversible contraception: two-year discontinuation, its risk factors, and reasons.

BACKGROUND: Since 2013, the residents of the city of Vantaa, Finland, have been offered their first long-acting reversible contraceptive method (levonorgestrel-releasing intrauterine system, implant, and copper intrauterine device) free of charge. OBJECTIVE: The primary aim of this study was to assess the 2-year cumulative discontinuation rates of long-acting reversible contraceptive methods when provided free of charge for first-time users in a real-world setting. Additional aims were to describe factors associated with discontinuation and to evaluate the reasons for discontinuation. STUDY DESIGN: This is a retrospective register-based cohort study of 2026 nonsterilized women aged 15 to 44 years, who initiated a free-of-charge long-acting contraceptive method in 2013-2014 in the city of Vantaa. Removals within 2 years after method initiation and reasons for discontinuation were obtained from electronic health records and from national registers. We calculated the 2-year cumulative incidence rates of discontinuation with 95% confidence intervals for each method. Furthermore, we assessed crude and adjusted incidence rate ratios of discontinuation with 95% confidence interval by Poisson regression models comparing implants and copper intrauterine device with levonorgestrel-releasing intrauterine systems. RESULTS: During the 2 -year follow-up, 514 women discontinued, yielding a cumulative discontinuation rate of 28.3 per 100 women-years (95% confidence interval, 26.2-30.4). Among the 1199 women who initiated the levonorgestrel-releasing intrauterine system, the cumulative discontinuation rate was 24.2 per 100 women-years (95% confidence interval, 21.7-26.9); among the 642 implant users, 33.3 per 100 women-years (95% confidence interval, 29.5-37.4); and among the 185 copper intrauterine device users, 37.8 per 100 women-years (95% confidence interval, 31.0-45.7). Compared with women aged 30 to 44 years, women aged 15 to 19 years (adjusted incidence rate ratio, 1.58; 95% confidence interval, 1.17-2.14) and 20 to 29 years (adjusted incidence rate ratio, 1.35; 95% confidence interval, 1.11-1.63) were more likely to discontinue. We observed a higher discontinuation rate in women who had given birth within the previous year (adjusted incidence rate ratio, 1.36; 95% confidence interval, 1.13-1.65), spoke a native language other than Finnish or Swedish (adjusted incidence rate ratio, 1.31; 95% confidence interval, 1.06-1.63), and had a history of a sexually transmitted infection (adjusted incidence rate ratio, 1.62; 95% confidence interval, 1.07-2.46). No association was found in marital status, overall parity, history of induced abortion, socioeconomic status, education level, or smoking status. The most common reason for discontinuation was bleeding disturbances, reported by 21% of women who discontinued the levonorgestrel-releasing intrauterine system, by 71% who discontinued the implant, and by 41% who discontinued the copper intrauterine device. One in 4 women who discontinued the copper intrauterine device reported heavy menstrual bleeding, whereas only 1% who discontinued the levonorgestrel-releasing intrauterine system and none who discontinued implants reported this reason. Abdominal pain was the reported reason for discontinuation in 20% of both intrauterine device users and in only 2% who discontinued implants. CONCLUSION: At 2 years, the use of implants and copper intrauterine devices was more likely to be discontinued than that of the levonorgestrel-releasing intrauterine system. Women younger than 30 years and those who gave birth in the preceding year, spoke a native language other than Finnish or Swedish, or had a history of sexually transmitted infections were more likely to discontinue. The levonorgestrel-releasing intrauterine system was least likely to be removed owing to bleeding disturbances.

Long-term use of dienogest for the treatment of primary and secondary dysmenorrhea.

AIM: To investigate the safety and efficacy of dienogest (DNG), a progestational 19-norsteroid, administered for 52 weeks in patients with primary and secondary dysmenorrhea. METHODS: A total of 147 patients with dysmenorrhea received 1 mg of DNG orally each day for 52 weeks. The dose could be increased to 2 mg/day at or after Week 12 according to the investigator's determination. The primary safety endpoint was evaluation of adverse events, and the secondary safety endpoint was evaluation of adverse drug reactions. The number of days and severity of genital bleeding were assessed according to records in the patients' diary. Lower abdominal pain and/or low back pain because of dysmenorrhea were assessed according to the dysmenorrhea score. RESULTS: The most frequent adverse drug reaction was irregular uterine bleeding (94.6%). Most subjects completed the 52-week administration. Genital bleeding was more likely to occur in subjects with secondary dysmenorrhea than in those with primary dysmenorrhea, and in subjects with "uterine myoma or adenomyosis" than in those with "endometriosis alone." In any of the categorizations, there tended to be fewer days with genital bleeding as the treatment period increased in length, and most of the genital bleeding cases were mild. The change from baseline in the dysmenorrhea score (mean ± standard deviation [SD]) was -3.7 ± 1.6 at Week 24 of treatment and -4.0 ± 1.3 at Week 52. CONCLUSION: This study showed favorable tolerability of the long-term use of DNG to patients with dysmenorrhea and a sustainable pain relief effect.

The influence of the levonorgestrel-releasing intrauterine system position on bleeding patterns in reproductive age women.

OBJECTIVE: To determine whether users of the non-fundal levonorgestrel-releasing intrauterine system (LNG-IUS) present with unfavorable bleeding patterns more frequently than fundal LNG-IUS users. METHODS: A prospective cohort was conducted from June, 2016 to January, 2018 involving women aged 18-45 years who wished to use the LNG-IUS as contraception and had no contraindications, endometrial polyps, submucosal myomas, irregular menstrual cycle, or anticoagulant use. Two study groups comprised women using fundal insertion and non-fundal insertion LNG-IUS. Bleeding was evaluated using a diary and pictogram chart. RESULTS: Of the 92 women who participated in the study, those with non-fundal LNG-IUS insertion sustained bleeding at rates greater than 83% (31) in the first 3 months of use, and 58% (14) at 6 months, versus 51% (22) at 3 months and 33% (19) at 6 months in those with fundal insertion (P=0.002 at 3 months; P=0.037 at 6 months). Blood loss in the non-fundal LNG-IUS group was higher than in the fundal LNG-IUS group according to pictograms drawn by participants. CONCLUSION: Women with non-fundal LNG-IUS placement had a higher frequency of sustained bleeding and blood loss volume according to self-reported charts than those with fundal LNG-IUS placement.

Symptom-alleviating effect and adverse effect of dienogest in Korean women with endometriosis.

The purpose was to evaluate the effects of dienogest on Korean women with endometriosis. A cross-sectional questionnaire-based survey was conducted for 100 premenopausal women. They had taken or were taking 2 mg of dienogest daily. We assessed the pelvic pain score and quality-of-life (QOL) score before and after taking dienogest as well as the prevalence of short-term (≤12 weeks) and long-term adverse effects (>52 weeks). Patients were classified into three groups: dienogest treatment immediately following surgery (A), dienogest treatment for a recurrence of endometriosis after surgery (B), or dienogest treatment without any surgery (C). In groups A and C, the median pain score (from 5 to 0, p <.001; from 7 to 1.5, p <.001) and median QOL score (from 10 to 5, p = .002; from 7.5 to 6.5, p = .008) were significantly decreased. Irregular bleeding and decreased menstrual flow were more prevalent in patients with dienogest intake of fewer than 12 weeks, while amenorrhea, weight gain, hair loss, and dorsal pain were more prevalent in patients with dienogest treatment of over 52 weeks. Accordingly, proper counseling is necessary when prescribing dienogest.

Recovery of reproductive function following androgen abuse.

PURPOSE OF REVIEW: To summarize recent data on the adverse reproductive consequences of androgen abuse, focusing on the recovery of reproductive function following androgen discontinuation. RECENT FINDINGS: Evidence is mostly based on case reports and observational studies. Androgen abuse leads to a state of hypogonadotropic hypogonadism associated with impaired spermatogenesis, testicular atrophy, gynecomastia as well as menstrual irregularities, virilization and subfertility. Recovery of the hypothalamic-pituitary-gonadal axis following androgen withdrawal depends on the type and characteristics of androgen administration (dose, duration of use) as well as those of the user (age, previous reproductive function). Biochemical and clinical features of hypogonadism may be evident months or even years following androgen discontinuation. To prevent androgen-related adverse effects and accelerate recovery of gonadal function, users take androgens in a cyclical fashion and use drugs such as human chorionic gonadotropin, antiestrogens and aromatase inhibitors, even though there is limited evidence to support efficacy of these strategies. As few studies refer to female androgen users, there is a lack of data concerning recovery from androgen-related reproductive side effects in women. SUMMARY: Androgen abuse has profound and commonly under-recognized effects on the reproductive system; recovery following androgen withdrawal may be prolonged and occasionally incomplete.

No. 329-Canadian Contraception Consensus Part 4 of 4 Chapter 9: Combined Hormonal Contraception.

OBJECTIVE: To provide guidelines for health care providers on the use of contraceptive methods to prevent pregnancy and on the promotion of healthy sexuality. OUTCOMES: Overall efficacy of cited contraceptive methods, assessing reduction in pregnancy rate, safety, and side effects; the effect of cited contraceptive methods on sexual health and general well-being; and the availability of cited contraceptive methods in Canada. EVIDENCE: Medline and the Cochrane Database were searched for articles in English on subjects related to contraception, sexuality, and sexual health from January 1994 to December 2015 in order to update the Canadian Contraception Consensus published February-April 2004. Relevant Canadian government publications and position papers from appropriate health and family planning organizations were also reviewed. VALUES: The quality of the evidence is rated using the criteria described in the Report of the Canadian Task Force on Preventive Health Care. Recommendations for practice are ranked according to the method described in this report. SUMMARY STATEMENTS: RECOMMENDATIONS.

The role of estrogen receptor subtypes for induction of delayed effects on the estrous cycle and female reproductive organs in rats.

It has been reported that neonatal exposure to estrogens at relatively low doses can induce early onset anovulation as a delayed effect in female rats. Dysfunction of kisspeptin neurons in the anteroventral periventricular nucleus (AVPV) was proposed to be a trigger for this effect. To determine the roles of estrogen receptor (ER) subtypes in the induction of delayed effects, we conducted a series of experiments using Donryu rats to examine whether neonatal injection of an ERα agonist (PPT), an ERß agonist (DPN) or an ERα antagonist (ICI) could induce delayed effects. Also, involvement of the kisspeptin neurons in the AVPV for induction of delayed effect by PPT and DPN was investigated. We observed that neonatal exposure to PPT, DPN and ICI induced the early onset of abnormal estrous cyclicity after sexual maturation, suggesting that the compounds capable of inducing delayed effects are not limited to ERα agonists. On the other hand, the data suggested the possibility that DPN and ICI functioned partially as ERα agonists in the neonatal brain. Regardless of the agents used, there is a possibility that dysfunction of kisspeptin neurons in the AVPV might contribute to induction of early onset anovulation.

Reproductive and metabolic abnormalities in women taking valproate for bipolar disorder: a meta-analysis.

OBJECTIVE: We aimed to evaluate the relationship between valproate (VPA) and reproductive endocrine abnormalities in women with bipolar disorder. METHODS: We searched studies in electronic databases of China Biology Medicine disc, PubMed, and Embase. Two authors collected articles and extracted data independently. Meta-analysis was performed for polycystic ovary syndrome (PCOS) and its components. The mean difference (MD) and 95% confidence interval (CI) were used to compare continuous variables. The Mantel-Haenszel formula was used to calculate the odds ratio (OR). RESULTS: There were statistically significant differences between the VPA treated and non-VPA treated groups in PCOS (OR 6.74; 95% CI 1.66-27.32; P=0.00), menstrual disorder (OR 1.81; 95% CI 1.02-3.23; P=0.04), and hyperandrogenism (HA) (OR 2.02; 95% CI 1.11-3.65; P=0.02). There was no statistically significant difference between the VPA treated and non-VPA treated groups in PCO (OR 1.37; 95% CI 0.71-2.66; P=0.35). The overall risk of menstrual disorders, PCO, and HA in the VPA treated group was higher than in the non-VPA treated group (OR 1.75; 95% CI 1.23-2.47; P=0.00). The levels of total and free testosterone in the VPA treated group were higher than in the non-VPA treated group (MD 0.12; 95% CI 0.05-0.19; P=0.00; MD 0.14, 95% CI 0.07-0.21; P=0.00, respectively). CONCLUSIONS: VPA was associated with the elevated levels of testosterone and HA in women with BD.

[Hyperprolactinemia associated with neuroleptic treatment: clinical characteristics and an impact on sexual function]. / Giperprolaktinemiya, assotsiirovannaya s priemom neiroleptikov: osobennosti klinicheskikh proyavlenii i vliyanie na seksual'nye funktsii.

AIM: To study clinical characteristics of antipsychotic-induced hyperprolactinemia (AIH) and an impact of AIH on sexual function in patients with mental disorders treated with neuroleptics for a long time. MATERIAL AND METHODS: A cross-sectional study of 244 consecutive psychiatric in-patients (F/M=140/104) with mental disorders currently taking antipsychotics was carried out. The patients were screened for serum prolactin, sex hormones and gonadotropin levels. The UKU Side effects rating scale (UKU) was used to assess side-effects. For assessment of sexual dysfunction, the Psychotropic-Related Sexual Dysfunction Questionnaire (PRSexDQ) was administered. RESULTS AND CONCLUSION: Asymptomatic AIH was found in 16% of females and in 37% of males. AIH caused menstrual disorders (oligomenorrhea and amenorrhea), galactorrhea in females. AIH was associated with libido decrease and life quality impairment due to sexual dysfunctions in patients of both genders. AIH was associated with orgasm delay and vaginal dryness during sexual intercourse in females. In men, AIH was associated with erectile dysfunction. In contrast to pituitary tumor and idiopathic hyperprolactinemia, there was no association between AIH and weight gain and/or obesity, and hypogonadism in patients of both genders.

[New Low-Dose Oral Contraceptive with 28 Midiana.]

As a representative of the low dose generation of oral contraceptives, Midiana 28 provides minimal intake of estrogens for the female organism in the presence of a new generation getation component- Drospierenone. Midiana has an excellent contraceptive effect - the control group of women showed no cases of impregnation during the intake, Pearl index =0.00. It also exercises a good control over the menstrual cycle with low frequency of intementrual bleeding /17%/ Midiana 28 shows a very good tolerability with minimal, detected, rapidly transient side effects.

Irregularidad menstrual y exposición a mercurio en la minería artesanal del oro en Colombia / Human mercury exposure and irregular menstrual cycles in relation to artisanal gold mining in Colombia

Introducción. El proceso de extracción del oro por amalgamación con mercurio es común en la minería artesanal. Los efectos sobre la reproducción de la exposición al mercurio elemental en el contexto de la minería del oro, no han sido suficientemente estudiados. Objetivo. Evaluar el efecto de la exposición al mercurio elemental durante la minería del oro, sobre la regularidad del ciclo menstrual y la presentación de abortos en Colombia. Materiales y métodos. Se hizo un estudio analítico de corte transversal. Las participantes residían en distritos de minería de oro con historia de exposición al mercurio elemental y se las comparó con un grupo de mujeres no expuestas, en cuanto a la regularidad del ciclo menstrual y la ocurrencia de abortos. Para el registro de las variables de exposición y resultado, se usó un cuestionario cuya reproducibilidad prueba-reprueba fue evaluada. Se calcularon las razones de prevalencia mediante un modelo binomial y se evaluó la bondad de ajuste. Resultados. Participaron 72 mujeres expuestas y 121 mujeres no expuestas al mercurio. Entre las mujeres expuestas, el tiempo promedio de exposición al mercurio fue de 19,58 ± 9,53 años. La prevalencia ajustada de menstruación irregular en los últimos seis meses, fue mayor en el grupo de mujeres expuestas crónicamente a vapores de mercurio (razón de prevalencia, RP=1,59, IC 95% 0,93-2,73), pero la proporción de mujeres con historia de abortos no fue diferente. Conclusiones. La exposición al mercurio elemental durante el proceso artesanal de la minería del oro podría estar asociada con una mayor prevalencia de irregularidad del ciclo menstrual, pero no con la presentación de abortos.

Introduction: Artisanal mining commonly extracts gold with an amalgamation process that uses mercury. The reproductive effects from exposure to elemental mercury used in gold mining have not been sufficiently studied. Objective: To evaluate the effect of the exposure to elemental mercury used in gold mining on menstrual cycle regularity and the occurrence of miscarriages in Colombia. Materials and methods: An analytical cross-sectional study was conducted. The participants were female residents of gold mining districts, with a history of exposure to elemental mercury. Menstrual regularity and the occurrence of miscarriages were compared between these women and an unexposed group. Exposure and outcome variables were registered based on a questionnaire which was evaluated for its test-retest reproducibility. Prevalence rates were calculated using a binomial model and goodness-of-fit was evaluated. Results: A total of 72 women exposed to mercury and 121 unexposed women participated. The average time of exposure to mercury among exposed women was 19.58 ± 9.53 years. The adjusted prevalence of irregular menstruation over the last six months was higher in the group of women chronically exposed to mercury vapors (PR=1.59, 95% CI 0.93-2.73), while there was no difference in the proportion of women with a history of miscarriages. Conclusions: Exposure to elemental mercury used in artisanal gold mining may be associated with a higher prevalence of irregular menstrual cycles but not with the occurrence of miscarriage.

General adverse response to cyclophosphamide in Chinese patients with systemic autoimmune diseases in recent decade­a single-center retrospective study.

This study was conducted to investigate the adverse reaction to cyclophosphamide (CYC) in Chinese patients with systemic autoimmune diseases. Patients with systemic autoimmune diseases who were exposed to CYC and followed up regularly for at least 2 years in Rheumatology Department during June 2003 to June 2013 were enrolled into this study. Participants were divided into per oral (PO) group and intravenous (IV) group. The adverse effects to CYC were recorded and analyzed. A total of 419 patients were enrolled in this study. The occurrence rates of gastrointestinal discomfort, alopecia, myelosuppression, secondary infection, abnormal liver function, dizziness/headache, menstrual disturbance and reversal to normal menstruation after discontinuation of CYC were 21.5%, 12.4%, 7.4 %, 3.6%, 3.1%, 3.1%, 30.3% and 31.0%, respectively. None of the patients had hemorrhagic cystitis. The significant risk factors for gastrointestinal discomfort were female, exposure to CYC for a long time and intravenous route. Risk factors for mylosuppression were female and combination with other immunosuppressants. Risk factors were female gender for alopecia and older age for menstrual disturbance. Female patients were much more likely to have gastrointestinal discomfort, mylosuppression and alopecia when CYC was administrated intravenously. Risk factors were older age for menstrual disturbance and the combination with other immunosuppressants for myelosuppression. Hemorrhagic cystitis did not appear in our series for the possible reason of prophylactic hydration before intravenous injection and maybe racial difference.

The risk of elevated prolactin levels in pediatric patients exposed to antipsychotics for the treatment of schizophrenia and schizophrenia spectrum disorders: protocol for a systematic review and meta-analysis.

BACKGROUND: Antipsychotic medications, particularly second-generation antipsychotics, are increasingly being used to alleviate the symptoms of schizophrenia and other severe mental disorders in the pediatric population. While evidence-based approaches examining efficacy and safety outcomes have been reported, no review has evaluated prolactin-based adverse events for antipsychotic treatments in schizophrenia and schizophrenia spectrum disorders. METHODS/DESIGN: Searches involving MEDLINE, EMBASE, CENTRAL, PsycINFO, and clinical trial registries (ClinicalTrials.gov, Drug Industry Document Archive [DIDA], International Clinical Trials Registry Platform [ICTRP]) will be used to identify relevant studies. Two reviewers will independently screen abstracts and relevant full-text articles of the papers identified by the initial search according to the prospectively defined eligibility criteria. Data extraction will be conducted in duplicate independently. Pairwise random effects meta-analyses and network meta-analyses will be conducted on individual drug and class effects where appropriate. DISCUSSION: This systematic review will evaluate prolactin-based adverse events of first- and second-generation antipsychotics in the pediatric population with schizophrenia and schizophrenia spectrum disorders. It will also seek to strengthen the evidence base of the safety of antipsychotics by incorporating both randomized controlled trials and observational studies. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42014009506.

Accidental overdose of travoprost.

PURPOSE: To report systemic symptoms after an overdose of travoprost. CASE REPORT: We report a patient who, instead of artificial tears, inadvertently used travoprost every 15 minutes for 7 hours after LASIK (laser-assisted in situ keratomileusis) surgery. She experienced abrupt, severe abdominal cramps and sudden, severe menstrual bleeding, which subsided quickly upon discontinuation of the drug. CONCLUSIONS: Because of the few systemic adverse effects, prostaglandin analogs are widely used for the treatment of glaucoma. Travoprost should be taken once daily; therefore, overdose is extremely uncommon. Systemic prostaglandins have been found to be mediators of uterine activity and are used to induce labor and terminate pregnancies. The high dose of this topical medication, as well as the compromised cornea, makes this case unique. The unusual circumstances observed in this case greatly expand our knowledge regarding the potential adverse effects of travoprost.