Use of Vitex agnus-castus in patients with menstrual cycle disorders: a single-center retrospective longitudinal cohort study.

PURPOSE: To evaluate clinical characteristics, quality of life (QoL) and effectiveness in patients with menstrual cycle disorders (MCDs) including abnormal uterine bleeding, dysmenorrhea and mastodynia/mastalgia related to premenstrual syndrome taking the Vitex agnus-castus (VAC) products Cyclodynon® or Mastodynon® in a real-world setting. METHODS: A single-center retrospective longitudinal cohort study (3 ± 1 months), using data obtained from healthcare data archive and telephone interviews. The main study variables were changes in bleeding, menstrual pain, breast tenderness and patients' QoL. RESULTS: Data from 1700 women with a mean age of 30.2 years (± 6.3) were analyzed. The most common MCDs were dysmenorrhea (43.8%) and mastodynia/mastalgia (21.1%). Three-month treatment with VAC extract substantially decreased the percentage of patients with irregular cycle (from 9.1% to 0.1%) and breast tenderness (from 39.9% to 0.8%). Improvement in bleeding intensity, frequency and menstrual pain was experienced by 83.4%, 79.2%, and 85.2% of the patients, respectively. When analyzed by disease category, these parameters improved in almost all dysmenorrhea patients, while they improved to a lesser extent in mastodynia/mastalgia patients. QoL improved in all aspects, but was reported by a higher proportion of dysmenorrhea patients compared to mastodynia/mastalgia patients. Treatment was overall well tolerated with a favorable safety profile. CONCLUSION: These real-world data demonstrate the effectiveness of the VAC-containing products Cyclodynon® and Mastodynon® in the three-month treatment of MCDs, with a pronounced improvement in key disease symptoms and QoL. Intriguingly, while QoL was generally greatly improved, the response to VAC therapy varied depending on the type of underlying MCD.

Menstrual Irregularities and Amenorrhea in Thyroid Eye Disease Patients Treated With Teprotumumab.

PURPOSE: To evaluate the rates of amenorrhea and menstrual irregularities in patients with active thyroid eye disease treated with teprotumumab. METHODS: A retrospective review was conducted of patients with active thyroid eye disease treated between 2020 and 2022 at a single institution. Female thyroid eye disease patients with regular menstruation at baseline who completed 8 infusions of teprotumumab were assessed. Patient-reported irregularities in menstruation or amenorrhea were recorded during routine clinic visits. Two sample t tests were used to assess differences between patients endorsing and denying menstrual irregularities. RESULTS: Twelve patients met the inclusion criteria. The mean age was 38.33 ± 9.6 years (range 25-53 years). The average follow-up after treatment completion was 11.43 months. Nine patients (75%) reported changes from their baseline menstruation. Four patients (33.3%) reported irregularities during treatment only. Three patients (25%) had persistence of irregularities after treatment; these patients regained normal cycles at an average of 3 months following teprotumumab completion. Two patients (16.7%) did not regain their normal cycles at the time of their last follow-up. One 53-year-old patient-reported persistent amenorrhea after treatment completion. One patient-reported menorrhagia at a 4-month follow-up. No significant age difference was found between patients with or without reported menstrual changes ( p = 0.43). CONCLUSION: Abnormalities of menstruation, including amenorrhea, were reported by 75% of patients treated with teprotumumab. These changes reverted to baseline after treatment in most affected patients.

[Complex therapy of psychosomatic disorders associated with the female reproductive cycle]. / Kompleksnaya terapiya psikhosomaticheskikh rasstroistv, assotsiirovannykh s reproduktivnym tsiklom zhenshchiny.

Psychosomatic disorders make a great contribution to the structure of reproductive health disorders in women. The purpose of this review was to analyze the available data on effective methods of therapy for psychosomatic disorders associated with the reproductive cycle of women - psychopharmacological, psychotherapeutic, non-drug biological, hormonal. The review summarizes the evidence in relation to the treatment of disorders such as: stress-related menstrual irregularities; premenstrual dysphoric disorder; perinatal affective disorders (especially depression); psychosomatic disorders of the involutionary period. General recommendations on the complex therapy of psychosomatic disorders associated with the menstrual cycle within the framework of an interdisciplinary team have been formed.

Relationship of Ethinylestradiol/Drospirenone Prescription on Work Productivity and Activity Impairment Among Women With Menstruation-Related Symptoms: A Multicenter Prospective Observational Study.

OBJECTIVE: The aim of the study is to examine changes in work productivity and daily activity impairment among women by starting ethinylestradiol (EE)/drospirenone (DRSP) for perimenstrual symptoms. METHODS: Participants were women who were newly prescribed EE/DRSP at 25 gynecological clinics in Japan. Eligible participants recorded daily intake of EE/DRSP and the Work Productivity Activity Impairment Questionnaire General Health every 2 weeks for 3 months by smartphone app. A linear mixed-effects model was used to see changes in work productivity impairment and activity impairment relative to baseline. RESULTS: A total of 222 participants were eligible. Work productivity impairment recovered by 20.0% (95% confidence interval, 14.1%-26.0%) at 1 m and maintained for 2 months. Activity impairment recovered by 20.1% (95% confidence interval, 15.5%-24.7%) at 1 m and thereafter. CONCLUSIONS: Improvements in work productivity and daily activities were observed at 1 m after EE/DRSP initiation, with a sustained effect thereafter.

Contraceptive Implant-Associated Bleeding in Adolescent/Young Adult Clinical Practice: Associated Factors, Management, and Rates of Discontinuation.

PURPOSE: To identify factors associated with bothersome implant-associated uterine bleeding, and to evaluate the impact of bleeding management on implant discontinuation. METHODS: We analyzed a quality improvement database of implant insertions (n = 825) at three adolescent/young adult programs and described individuals with and without reported bothersome bleeding. We utilized logistic regression to assess for factors associated with bleeding. RESULTS: Implant recipient mean age was 18.9 ± 2.6 years, and 27% reported having subsequent bothersome uterine bleeding. Recipients had increased odds of reporting such bleeding if they had previously irregular menses (odds ratio [OR] = 1.36; 95% confidence interval [CI]: 1.11-1.68 irregular and infrequent, OR = 1.41; 95% CI: 1.07-1.86 irregular and frequent) or sought the implant for menstrual management purposes exclusively (OR = 1.67; 95% CI 1.42-1.96) or in combination with contraceptive need (OR 1.65; 95%: CI 1.57-1.72). Prior use of the progestin injection or implant was associated with lower odds of subsequent bleeding report (OR = 0.63; 95% CI: 0.54-0.73; OR = 0.54; 95% CI: 0.39-0.75, respectively). Medication management of bleeding was associated with the likelihood of implant discontinuation at 1 year compared to those with untreated bleeding (hazard ratio 1.98 times, 95% CI: 1.39-2.81). The implant was continued for 3 years in over 50% of recipients with ever-managed bothersome bleeding. DISCUSSION: Individuals with historically irregular menses and those seeking the implant for menstrual management more often reported bothersome bleeding. Treating such bleeding with medication was associated with higher 1-year discontinuation rates, although many continued implant use for 3 years. Such findings may influence implant preinsertion counseling and/or postinsertion bleeding management.

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.

Polycystic Ovary Syndrome in Adolescence: Challenges in Diagnosis and Management.

Diagnosing polycystic ovary syndrome (PCOS) during adolescence is challenging since normal pubertal development overlap typical features of this syndrome. The authors aim to summarize the existing evidence concerning PCOS in adolescence, particularly its diagnostic criteria and therapeutic options. A search throughout medical databases such as PubMed and MedScape was performed. Diagnostic criteria include irregular menstrual cycles according to time postmenarche and evidence of clinical hyperandrogenism and/or biochemical hyperandrogenism, provided other causes have been excluded. Polycystic ovarian morphology ought not to be used as a diagnostic criterion. Treatment should target manifestations and/or comorbidities, even in the absence of a definite diagnosis. Lifestyle interventions are the first-line treatment. Combined oral contraceptives, metformin or antiandrogens may also be considered as adjuvants. Screening for PCOS in adolescence is crucial as it allows an early intervention on the symptoms and comorbidities presented leading to better long-term reproductive and metabolic outcomes.

Diagnosticar a síndrome do ovário policístico (SOP) durante a adolescência é um desafio, uma vez que o desenvolvimento puberal normal se sobrepõe às características típicas desta síndrome. Os autores têm por objetivo resumir as evidências existentes sobre a SOP na adolescência, particularmente seus critérios diagnósticos e opções terapêuticas. Uma pesquisa em bases de dados médicas como PubMed e MedScape foi realizada. Os critérios de diagnóstico incluem ciclos menstruais irregulares de acordo com o tempo pós-menarca e evidência de hiperandrogenismo clínico e/ou hiperandrogenismo bioquímico, após exclusão de outras causas. A morfologia policística dos ovários não deve ser usada como um critério diagnóstico. O tratamento deve ser direcionado às manifestações e/ou comorbilidades, mesmo na ausência de um diagnóstico definitivo. As intervenções no estilo de vida são o tratamento de primeira linha. Contraceptivos orais combinados, metformina ou antiandrogênios também podem ser considerados como adjuvantes. O rastreamento da SOP na adolescência é fundamental, pois permite uma intervenção precoce ao nível dos sintomas e comorbilidades presentes levando a melhores resultados reprodutivos e metabólicos a longo prazo.

Effects of hormone replacement therapy on glucose and lipid metabolism in peri- and postmenopausal women with a history of menstrual disorders.

BACKGROUND: Previous studies have indicated that women with a history of menstrual disorders have an increased risk of metabolic and cardiovascular diseases. This has been attributed to the high proportion of polycystic ovary syndrome (PCOS) among this group. The favorable effects of hormone replacement therapy (HRT) on serum lipid profiles and glucose homeostasis in postmenopausal women is widely accepted. Whether HRT can also show positive effects on metabolic homeostasis in menopausal women with prior menstrual disorders (a putative PCOS phenotype) has not been reported yet. The aim of the study was to compare the effects of HRT on glucose and lipid metabolism in peri- and postmenopausal women with prior menstrual disorders and controls who did not have prior menstrual disorders. METHODS: A retrospective multicenter study was conducted including 595 peri- and postmenopausal women who received HRT at four hospitals in the Zhejiang Province from May 31, 2010 to March 8, 2021. Participants were divided into the Normal menstruation group and the Menstrual disorders group according to their prior usual menstrual cycle pattern. Glucose and lipid metabolism indicators were assessed at baseline and after HRT. The results were compared between and within the groups, and data from peri- and postmenopausal women were analyzed separately. RESULTS: HRT significantly decreased fasting insulin and homeostasis model assessment of insulin resistance in perimenopausal users, and fasting plasma glucose levels in postmenopausal users with prior menstrual disorders, compared with baseline. Furthermore, HRT decreased low-density lipoprotein cholesterol, total cholesterol, fasting insulin, fasting plasma glucose and homeostasis model assessment of insulin resistance in both peri- and postmenopausal controls, compared with baseline. Nevertheless, no significant differences were observed in any of the glucose or lipid metabolism indicators at baseline and follow-up, as well as changes from baseline levels between menopausal women with and without prior menstrual disorders. CONCLUSIONS: HRT shows more obvious within-group improvements in glucose and lipid metabolism in controls, but there is no significant between-group difference. Further prospective studies are required for confirmation.

Dydrogesterone indications beyond menopausal hormone therapy: an evidence review and woman's journey.

Dydrogesterone is an orally active synthetic progestogen, with a molecular structure similar to that of natural progesterone. As dydrogesterone does not inhibit ovulation at standard doses, is devoid of estrogenic or androgenic properties, and does not induce metabolic side effects, it is suitable for use throughout a woman's lifetime, from adolescence to older age, for conditions associated with altered levels of endogenous progesterone. Aside from its well established role as a component of menopausal hormone therapy, dydrogesterone is indicated in younger women for treatment of dysmenorrhea, irregular menstrual cycles, premenstrual syndrome, and threatened or recurrent miscarriage; and is effective as luteal phase support during assisted reproduction techniques. In this narrative review, evidence is examined for use of dydrogesterone across a range of disorders affecting menses and pregnancy. A case study woven into the review illustrates the clinical uses of dydrogesterone during a young woman's journey to become a mother.

Rare case of red tears: ocular vicarious menstruation.

Bloody tears or haemolacria is a rare clinical entity. It is caused by various ocular and systemic conditions. Haemolacria due to vicarious menstruation is even rarer. In this article, we presented a case of cyclical episodes of bloody tears coinciding with menstrual cycle in a 25-year-old married female patient. Extensive physical, ophthalmological and radiological evaluation failed to reveal other potential causes of her complaint. A diagnosis of ocular vicarious menstruation was made and she was treated with oral contraceptive pills. No such episode recurred during 3 months follow-up period.

Features of Menstruation and Menstruation Management in Individuals with Rett Syndrome.

STUDY OBJECTIVE: To describe features of menstruation, menstrual-related symptoms, and menstrual management in females with Rett syndrome (RTT) to help develop a clinical approach to these parameters in RTT. DESIGN: Retrospective cross-sectional chart review and prospective survey. SETTING: Cincinnati Children's Hospital Medical Center, Rett Syndrome and Related Spectrum Disorders Clinic. PARTICIPANTS: Females with RTT (12-55 years of age) and their caregivers. MAIN OUTCOME MEASURES: Descriptive data on features of menstruation and menstrual-related symptoms in individuals with Rett syndrome; prevalence, types, reason for use/discontinuation, and efficacy of hormonal treatment in females with RTT. RESULTS: Age at menarche, menstrual cycle length, and menstrual period length in females with RTT are comparable to those in typically developing females and females with other neurodevelopmental disabilities. Dysmenorrhea and emotional lability are common menstrual cycle-related changes among females with RTT; 22.1% of participants also reported catamenial seizures. Oral progestin, combined oral contraceptive pill, and depot-medroxyprogesterone acetate (DMPA) were effectively used to suppress or regulate menstruation and to manage menstrual-related symptoms. CONCLUSIONS: Characteristics of menstruation in females with RTT are comparable to those of typically developing females, with the exception of increase in catamenial seizure activity. Hormonal treatments are used for management of menstruation, dysmenorrhea, and seizures. Choice of hormonal treatment is influenced by bone health and immobility in females with RTT.

Ulipristal acetate use in adenomyosis: A randomized controlled trial.

OBJECTIVE: To evaluate the effect of a 10 mg per day 12 week treatment of ulipristal acetate (UPA) on abnormal uterine bleeding due to adenomyosis. DESIGN: A double-blind phase 2 randomized controlled pilot study. SETTING: From May 2015 to February 2018 in five teaching hospitals. POPULATION: Premenopausal women with abnormal uterine bleeding (with a pictorial blood loss assessment score (PBAC) higher than 100 at inclusion) and a sonographic or MRI diagnosis of adenomyosis. METHODS: After random allocation, either UPA 10 mg or placebo were orally administered during 12 weeks. A 3:1 ratio was used. MAIN OUTCOME MEASURES: The primary outcome was the rate of women with a PBAC score of less than 75 as evaluated over the 28 days following the 12-week treatment. Secondary outcomes included rate of amenorrhea, evolution of pain, quality of life and tolerance. RESULTS: Thirty women were included in the UPA group and 10 in the placebo group. No woman in the placebo group versus 95.24 % of women in the UPA group had a PBAC score under 75 during the 28 day period following the 12-week treatment (p < 0.01). A significant decrease in pain was noticed between inclusion and 13 weeks in the UPA group (p < 0.01). At 6 months, there was no significant difference in PBAC score or pain between groups. No serious adverse event was recorded. CONCLUSION: UPA could be an interesting option for treatment of abnormal uterine bleeding related to adenomyosis in women wishing to preserve their fertility.

Dietary Supplementation of Lauric Acid Alleviates the Irregular Estrous Cycle and the Impaired Metabolism and Thermogenesis in Female Mice Fed with High-Fat Diet (HFD).

Lauric acid (LA) has been implicated in the prevention/treatment of obesity. However, the role of LA in modulating an obesity-related female reproductive disorder remains largely unknown. Here, female mice were fed a control diet, high-fat diet (HFD), or HFD supplemented with 1% LA. The results demonstrated that the HFD-induced estrous cycle irregularity and the reduction of serum follicle-stimulating hormone (FSH) were alleviated by LA supplementation. In possible mechanisms, LA supplementation led to significant increase in serum lipid metabolites such as sphingomyelin and lysophosphatidylcholine containing LA (C12:0) and the improvement of glucose metabolism in mice fed HFD. Moreover, impaired body energy metabolism and weakened brown adipose tissue (BAT) thermogenesis of HFD-fed mice were improved by LA supplementation. Together, these findings showed that LA supplementation alleviated HFD-induced estrous cycle irregularity, possibly associated with altered serum lipid metabolites, improved glucose metabolism, body energy metabolism, and BAT thermogenesis. These findings suggested the potential application of LA in alleviating obesity and its related reproductive disorders.

Uncovering the pharmacological mechanism of motherwort (Leonurus japonicus Houtt.) for treating menstrual disorders: A systems pharmacology approach.

Leonurus japonicus (motherwort) is a traditional Chinese medicine that is widely used to treat menstrual disorders (MDs). However, the pharmacological mechanisms that underlie its clinical application remain unclear. In this study, a network pharmacology-based approach was used that integrated drug-likeness evaluation, oral bioavailability prediction, target exploration, network construction, bioinformatic annotation and molecular docking to investigate the mechanisms that underlie motherwort treatment for MDs. In total, 29 bioactive compounds were collected from 51 compounds in motherwort, which shared 17 common MDs-related targets. Network analysis indicated that motherwort played a therapeutic role in MDs treatment through multiple components that acted on multiple targets. Pathway enrichment analysis showed that the putative targets of motherwort were primarily involved in various pathways associated with the endocrine system, cancers, vascular system, and anti-inflammation process. Notably, five targets (i.e., AKT1, PTGS2, ESR1, AR and PPARG) were screened as hub genes based on a degree algorithm. Moreover, most of the bioactive components in motherwort had good binding ability with these genes, implying that motherwort could regulate their biological function. Collectively, this study elucidated the molecular mechanisms that underlay the efficiency of motherwort against MDs and demonstrated the potential of network pharmacology as an approach to uncover the action mechanism of herbal medicines.

Menstrual Dysfunction and Treatment Among Adolescents With Congenital Heart Disease.

STUDY OBJECTIVE: This study describes menstrual dysfunction and treatment among adolescent and young adult (AYA) females with congenital heart disease (CHD). DESIGN: Data collected from a 1-time survey completed by AYA females (and mothers if AYA unable). SETTING: Participants were recruited from pediatric cardiology clinics. PARTICIPANTS: Female AYA with CHD, aged 14-21 years (N = 114). INTERVENTIONS: None. MAIN OUTCOME MEASURES: The questionnaire assessed sexual and reproductive health (SRH) concerns, behaviors, and management. Outcome measures were self-reported menstrual complaints, use of over-the-counter (OTC) pain relief medications for dysmenorrhea, reported visits with a clinician for a menstrual problem, and reported use of hormones for menstrual problems or birth control. RESULTS: Mean age was 17.0 years (SD = 2.2). The majority of participants (83%) reported 1 or more menstrual complaints (67.5% cramping, 42.1% irregular menses, 46.5% heavy periods), and 88% reported any history of taking OTC medications for pain relief. Increased menstrual complaints were not associated with level of cardiac complexity, reported transplantation, or reported use of hormonal contraception. However, 32% of participants reported use of hormonal contraception for menstrual dysfunction. Combined oral contraceptive pills (COCs) were the most common; 2 of these women carried contraindications to estrogen. CONCLUSIONS: A large majority of AYA females with CHD reported menstrual dysfunction. Use of OTC medication for menstrual pain and inappropriate use of estrogen creates concerns that menstrual disorders may be unaddressed or addressed inappropriately. Thus, gynecological needs of adolescents with CHD may need to be specifically targeted by providers who feel comfortable with this population and their complex needs.

Metformin versus the combined oral contraceptive pill for hirsutism, acne, and menstrual pattern in polycystic ovary syndrome.

BACKGROUND: Metformin has been proposed as possibly a safer and more effective long-term treatment than the oral contraceptive pill (OCP) in women with polycystic ovary syndrome (PCOS). It is important to directly compare the efficacy and safety of metformin versus OCP in the long-term treatment of women with PCOS. This is an update of a Cochrane Review comparing insulin sensitising agents with the OCP and only includes studies on metformin. OBJECTIVES: To assess the effectiveness and safety of metformin versus the OCP (alone or in combination) in improving clinical, hormonal, and metabolic features of PCOS. SEARCH METHODS: In August 2019 we searched the Cochrane Gynaecology and Fertility Group Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase and CINAHL, the trial registers, handsearched references of the identified articles, and contacted experts in the field to identify additional studies. SELECTION CRITERIA: We included randomised controlled trials (RCTs) of the use of metformin versus the OCP (alone or in combination) for women with PCOS. DATA COLLECTION AND ANALYSIS: We used standard methods recommended by Cochrane. The primary review outcomes were the clinical parameters of hirsutism and adverse events, both severe (requiring stopping of medication), and minor. In the presence of substantial heterogeneity (I2 statistic > 50), which could be explained by pre-specified subgroup analyses on the basis of BMI, we reported the subgroups separately. MAIN RESULTS: This is a substantive update. We identified 38 additional studies. We included 44 RCTs (2253 women), which comprised 39 RCTs on adult women (2047 women) and five RCTs on adolescent women (206 women). Evidence quality ranged from very low to low. The main limitations were risk of bias, imprecision and inconsistency. Metformin versus the OCP In adult women, we are uncertain of the effect of metformin compared to the OCP on hirsutism in subgroup body mass index (BMI) < 25 kg/m2 (mean difference (MD) 0.38, 95% confidence interval (CI) -0.44 to 1.19, 3 RCTs, n = 134, I2 = 50%, very low-quality evidence) and subgroup BMI > 30 kg/m2 (MD -0.38, 95% CI -1.93 to 1.17; 2 RCTs, n = 85, I2 = 34%, low-quality evidence). Metformin may be less effective in improving hirsutism compared to the OCP in the subgroup BMI 25 kg/m2 to 30 kg/m2 (MD 1.92, 95% CI 1.21 to 2.64, 5 RCTs, n = 254, I2 = 0%, low-quality evidence). Metformin may increase severe gastro-intestinal adverse events rate compared to the OCP (Peto odds ratio (OR) 6.42, 95% CI 2.98 to 13.84, 11 RCTs, n = 602, I2 = 0%, low-quality evidence). Metformin may decrease the incidence of severe other adverse events compared to the OCP (Peto OR 0.20, 95% CI 0.09 to 0.44, 8 RCTs, n = 363, I2 = 0%, low-quality evidence). There were no trials reporting on minor adverse events. In adolescents, we are uncertain whether there is a difference between Metformin and the OCP, on hirsutism and adverse events. Metformin versus metformin combined with the OCP In adult women, metformin may be less effective in improving hirsutism compared to Metformin combined with the OCP (MD 1.36, 95% CI 0.62 to 2.11, 3 RCTs, n = 135, I2= 9%, low-quality evidence). We are uncertain if there was a difference between metformin and metformin combined with the OCP for severe gastro-intestinal adverse events (OR 0.74, 95% CI 0.21 to 2.53, 3 RCTs, n = 171, I2 = 0%, low-quality evidence), or for severe other adverse events (OR 0.56, 95% CI 0.11 to 2.82, 2 RCTs, n = 109, I2 = 44%, low-quality evidence). There were no trials reporting on minor adverse events. In adolescents, there were no trials for this comparison. The OCP versus metformin combined with the OCP In adult women, the OCP may be less effective in improving hirsutism compared to metformin combined with the OCP (MD 0.54, 95% CI 0.20 to 0.89, 6 RCTs, n = 389, I2= 1%, low-quality evidence). The OCP may decrease the incidence of severe gastro-intestinal adverse events compared to metformin combined with the OCP (OR 0.20, 95% CI 0.06 to 0.72, 5 RCTs, n = 228, I2 = 0%, low-quality evidence). We are uncertain if there is a difference between the OCP and metformin combined with the OCP for severe other adverse events (OR 1.61, 95% CI 0.49 to 5.37, 4 RCTs, n = 159, I2 = 12%, low-quality evidence). The OCP may decrease the incidence of minor (gastro-intestinal) adverse events compared to metformin combined with the OCP (OR 0.06, 95% CI 0.01 to 0.44, 2 RCTs, n = 98, I2 = 0%, low-quality evidence). In adolescents, we are uncertain whether there is a difference between the OCP, compared to metformin combined with the OCP, on hirsutism or adverse events. AUTHORS' CONCLUSIONS: In adult women with PCOS, metformin may be less effective in improving hirsutism compared to the OCP in the subgroup BMI 25 kg/m2 to 30 kg/m2 but we are uncertain if there was a difference between metformin and the OCP in subgroups BMI < 25 kg/m2 and BMI > 30kg/m2. Compared to the OCP, metformin may increase the incidence of severe gastro-intestinal adverse events and decrease the incidence of severe other adverse events with no trials reporting on minor adverse events. Either metformin alone or the OCP alone may be less effective in improving hirsutism compared to metformin combined with the OCP. We are uncertain whether there is a difference between the OCP alone and metformin alone compared to metformin combined with the OCP for severe or minor adverse events except for the OCP versus metformin combined with the OCP where the OCP may decrease the incidence of severe and minor gastro-intestinal adverse events. In adolescent women with PCOS, we are uncertain whether there is a difference between any of the comparisons for hirsutism and adverse events due to either no evidence or very low-quality evidence. Further large well-designed RCTs that stratify for BMI are needed to evaluate metformin versus the OCP and combinations in women with PCOS, in particular adolescent women.

Epidemiology and Treatment of Menstrual Migraine and Migraine During Pregnancy and Lactation: A Narrative Review.

The peak prevalence of migraine occurs in women of reproductive age, and women experience a higher burden of migraine symptoms and disability compared to men. This increased burden of migraine in women is related to both developmental and temporally variable activational effects of female sex hormones. Changing levels of female sex hormones affect the expression of migraine during pregnancy, and, to a lesser degree, lactation, and are the mechanism underlying menstrual migraine. This review describes the evidence for sex differences in the expression of migraine across the reproductive epoch; reviews the epidemiology of migraine during pregnancy, lactation, and menses; and summarizes the available evidence for safety and efficacy of acute treatments during pregnancy and lactation and for menstrual migraine. Areas of controversy in treatment of migraine during pregnancy, including the use of magnesium, triptans vs butalbital combination medications, and onabotulinum toxin, are also explored.

Regulation effect and mechanism of Sheng-Hua-Tang on female reproductive system: From experimental transcriptomic analysis to clinical applications.

ETHNOPHARMACOLOGICAL RELEVANCE: Sheng-Hua-Tang (SHT) is commonly used to treat female illnesses, especially postpartum conditioning. However, its effects and mechanisms on female reproductive system remain unclear. The aim of the present study was to investigate the effect of SHT on female brain-ovary-uterus axis from bench to clinic. MATERIALS AND METHODS: Mice were administrated SHT (200 mg/kg) orally for seven consecutive days. Brain, ovary, and uterus tissues were then collected for microarray analysis. A nationwide database analysis and a pilot randomized, open-label clinical trial were further applied to evaluate the clinical application and effects of SHT on postpartum women. RESULTS: Microarray analysis showed that oral administration of SHT induced a cascade reaction of gene expression, with 17, 883, and 1592 genes were significantly regulated by SHT in brain, ovary, and uterus, respectively. Population-based analysis of one million subjects in Taiwan's National Health Insurance Research Database between 1997 and 2013 showed that SHT was commonly used in menstrual disorders in female population, especially dysmenorrhea, abnormal uterine bleeding, and variation of menstrual cycle. Clinical trial on postpartum women showed that oral administration SHT for one week alleviated uterine contraction pain and breast swelling pain. Furthermore, Mmp2, Mmp3, Mmp9, Mmp11, Mmp15, Oxtr, Plrl, and Tph2 gene expression affected by SHT in mice were correlated with clinical effects of SHT in human subjects. CONCLUSION: This report provided the scientific evidences of mechanisms and clinical efficacies of SHT. Moreover, our findings might afford insights for clinical doctors in terms of SHT prescription.