Prediction of menstrual recovery patterns in premenopausal women with breast cancer taking tamoxifen after chemotherapy: an ASTRRA Substudy.

BACKGROUND: Chemo-endocrine therapy can lead to various side effects associated with ovarian dysfunction. Predicting menstrual recovery is necessary to discuss the treatment-related issues regarding fertility and premature menopause with patients. METHODS: In the ASTRRA trial, patients who resumed ovarian function within 2 years after chemotherapy were randomized to receive tamoxifen for 5 years or OFS with tamoxifen for 2 years. With these 1298 patients, we developed a model that predicts when menstrual recovery will occur within a 3-year period after chemotherapy using variables including age, body mass index, chemotherapy regimen and duration, and serum estradiol and follicle-stimulating hormone levels. RESULTS: The data of 957 patients were used to develop the prediction model, and those of 341 patients were used for validation. In the development group, menstruation resumed in 450 patients (47.0%) within 5 years. In multivariable analysis, younger age (< 35 vs. 45, HR 7.85, 95% CI 4.63-13.30, p < 0.0001), anthracycline-based chemotherapy without taxane (vs. with taxane, HR 1.81, 95% CI 1.37-2.38, p < 0.0001), and chemotherapy duration (≤ 90 days vs. > 90 days, HR 1.32, 95% CI 1.01-1.72, p = 0.045) correlated with menstrual recovery. Using combined age, regimen, and duration of chemotherapy, we developed a simplified scoring system to estimate recovery chances and used a concordance index of 0.679 overall and 0.744 at 3 years for validation. CONCLUSION: This model predicted timing and probability of menstrual recovery, based on their individual age, type and duration of chemotherapy in premenopausal women diagnosed with breast cancer who received tamoxifen after chemotherapy.

Outcomes of Vaginal Repair and Vaginal Repair Combined With GnRHa Administration in the Treatment of Cesarean Section Scar Defects: A Randomized Clinical Trial.

STUDY OBJECTIVE: To prospectively investigate whether the application of vaginal repair (VR) of cesarean section scar defect (CSD) combined with a gonadotropin-releasing hormone agonist (GnRHa) achieve better clinical outcomes than VR alone. DESIGN: A randomized clinical trial. SETTING: University Hospital. PATIENTS: A total of 124 women with CSD were undergoing expectant management from December 2016 to September 2021. 61 were randomized to VR+ GnRHa and 63 to VR alone. INTERVENTION: Vaginal repair combined with GnRHa and vaginal repair alone. MEASURES AND MAIN RESULTS: The primary outcome was the duration of menstruation and thickness of the remaining muscular layer (TRM) at 6 months after surgery. Secondary outcomes included the length, width, and depth of the CSD; operation time; estimated blood loss; hospitalization time; and operative complications. Women were treated with either VR (n = 63) or VR + GnRHa (n = 61). Menstruation and TRM in patients pre vs post comparisons either with VR or VR + GnRHa are significantly improved (p <.05). Significant differences in menstruation duration and TRM occurred in patients treated with VR + GnRHa compared with those treated with VR (p <.05). Moreover, the rate of CSD after surgery in the VR group was significantly higher than that in the VR + GnRHa group (p = .033), and CSD patients in the VR + GnRHa group achieved better therapeutic effects than those in the VR group (p = .017). Patients who received VR + GnRHa had a shorter menstruation duration and a greater increment of TRM postoperatively than patients treated with VR alone (p = .021; p = .002, respectively). CONCLUSION: VR + GnRHa therapy has a greater potential to improve scar healing and reduce the number of menstruation days than VR alone for symptomatic women with CSD.

A systematic approach to the management of menses prophylaxis and suppression in pre-menopausal hematologic cancer patients.

OBJECTIVE: Hematologic malignancies in women of reproductive age carry significant additional morbidity due to menstrual bleeding in conjunction with disease and treatment-associated cytopenias. Several agents for menses prophylaxis and suppression exist, but there is a paucity of data comparing these therapies, particularly in the cancer setting. DATA SOURCES: A thorough literature review and evaluation of available data was conducted via PubMed search and combined with clinical expertise. DATA SUMMARY: The goal of prophylaxis therapy is to induce amenorrhea until it is considered safe to resume menstrual cycles. GnRH agonists remain the management of choice in achieving menses control and amenorrhea. Suppression is more likely achieved when the therapy is initiated in the late luteal phase or with the concomitant use of oral contraceptives. The effective use of oral contraceptives is achievable in appropriately selected patients. Although attractive as prophylactic agents, GnRH agonists have a slow onset of amenorrhea and can be associated with an initial increase in bleeding, thus are of limited value in immediate menorrhagia management. We recommend prioritizing estrogen therapy given its documented efficacy, and adding tranexamic acid as a secondary agent for severe or refractory bleeding. CONCLUSIONS: Thus far in the literature, this is the most comprehensive proposed pathway for the prevention and suppression of menorrhagia in hematologic cancer patients. Our protocol provides a step-wise approach for the management of menses prophylaxis and suppression to provide standardization amongst clinicians and adaptations for patient-specific needs.

Cartilage defect repair in a rat model via a nanocomposite hydrogel loaded with melatonin-loaded gelatin nanofibers and menstrual blood stem cells: an in vitro and in vivo study.

Cartilage damage caused by injuries or degenerative diseases remains a major challenge in the field of regenerative medicine. In this study, we developed a composite hydrogel system for the delivery of melatonin and menstrual blood stem cells (MenSCs) to treat a rat model of cartilage defect. The composite delivery system was produced by incorporation of melatonin into the gelatin fibers and dispersing these fibers into calcium alginate hydrogels. Various characterization methods including cell viability assay, microstructure studies, degradation rate measurement, drug release, anti-inflammatory assay, and radical scavenging assay were used to characterize the hydrogel system. MenSCs were encapsulated within the nanocomposite hydrogel and implanted into a rat model of full-thickness cartilage defect. A 1.3 mm diameter drilled in the femoral trochlea and used for the in vivo study. Results showed that the healing potential of nanocomposite hydrogels containing melatonin and MenSCs was significantly higher than polymer-only hydrogels. Our study introduces a novel composite hydrogel system, combining melatonin and MenSCs, demonstrating enhanced cartilage repair efficacy, offering a promising avenue for regenerative medicine.

Assessing the impact of hormonal contraceptive use on menstrual health among women of reproductive age - a systematic review.

BACKGROUND: Contraceptive methods are well-established in their ability to prevent pregnancy and increase individual agency in childbearing. Evidence suggests that contraceptives can also be used to treat adverse conditions associated with menstruation, including abnormal and prolonged uterine bleeding, heavy menstrual bleeding, painful menstruation, endometriosis, uterine fibroids, and premenstrual dysphoric disorders.This review investigates the effects of contraceptive techniques such as contraceptive pills, and long-acting reversible contraceptives (e.g. intrauterine devices, implants) on menstrual morbidity. METHODS: Over ten databases with no geographical boundaries were searched from inception until October 2023. Study designs were one of the following types to be included: parallel or cluster randomised controlled trials, controlled clinical trials, controlled before and after studies, interrupted time series studies, cohort or longitudinal analyses, regression discontinuity designs, and case-control studies. Ten team members screened the papers in pairs with a Kappa score of more than 7, and Covidence was used. Conflicts were resolved by discussion, and the full papers were divided among the reviewers to extract the data from eligible studies. RESULTS: Hormonal contraceptives are considered a well-tolerated, non-invasive, and clinically effective treatment for abnormal and prolonged uterine bleeding, heavy menstrual bleeding, painful menstruation, endometriosis, uterine fibroids, and premenstrual dysphoric disorders. Our studies investigating quality of life or well-being in women with heavy menstrual bleeding, endometriosis, or uterine fibroids have found improvements in all dimensions assessed. CONCLUSIONS: Hormonal contraceptives significantly reduce pain, symptom severity, and abnormal bleeding patterns associated with women who suffer from heavy menstrual bleeding, endometriosis, and uterine fibroids.

Hormonal contraceptives significantly reduce pain, symptom severity, and abnormal bleeding patterns associated with women who suffer from heavy menstrual bleeding, endometriosis, and uterine fibroids. Findings can inform clinical practice and policy decisions to ensure that women have access to safe and effective contraceptive options that promote both reproductive and non-reproductive health.

Predicting menstrual bleeding patterns with levonorgestrel-releasing intrauterine systems.

PURPOSE: To develop a bleeding-pattern prediction model to inform counselling on amount and regularity of bleeding after levonorgestrel-releasing intrauterine system (LNG-IUS) placement. MATERIALS AND METHODS: Fixed-cluster and regression-tree models were developed using bleeding data pooled from two clinical trials of LNG-IUSs. Models were trained and cross-validated on LNG-IUS 12 data, then applied to LNG-IUS 20 and LNG-IUS 8 data. Three clusters were generated for the fixed-cluster model: predominantly amenorrhoea; predominantly spotting; and predominantly bleeding. A random-forest model predicted the future-bleeding cluster, then the probability of cycle regularity was calculated. In the regression-tree model, women were assigned by the model to less- or more-bleeding groups. RESULTS: With LNG-IUS 12 (n = 1351) in the fixed-cluster model, 70.4% of women were correctly classified. The correct classification rates for LNG-IUS 20 (n = 216) and LNG-IUS 8 (n = 1300) were 72.2% and 69.0%. The probability distribution for cycle regularity showed regular and irregular bleeding were best separated with LNG-IUS 12 data, and less well with LNG-IUS 20 and LNG-IUS 8 data. In the regression-tree model there was high variability in the more- and less-bleeding group distributions with LNG-IUS 12 data. CONCLUSIONS: A fixed-cluster model predicted bleeding patterns better than a regression-tree model in women using LNG-IUS, yielding understandable, informative output.

Progestogens or progestogen-releasing intrauterine systems for uterine fibroids (other than preoperative medical therapy).

BACKGROUND: Uterine fibroids can cause heavy menstrual bleeding. Medical treatments are considered to preserve fertility. It is unclear whether progestogens or progestogen-releasing intrauterine systems can reduce fibroid-related symptoms. This is the first update of a Cochrane Review published in 2013. OBJECTIVES: To determine the effectiveness of progestogens or progestogen-releasing intrauterine systems in treating premenopausal women with uterine fibroids. SEARCH METHODS: We searched the Cochrane Gynaecology and Fertility Group Specialised Register, CENTRAL, MEDLINE, Embase, and PsycINFO databases to July 2020. We also searched trials registers for ongoing and registered trials, and checked references of relevant trials. SELECTION CRITERIA: All identified published or unpublished randomised controlled trials (RCTs) assessing the effect of progestogens or progestogen-releasing intrauterine systems in treating premenopausal women with uterine fibroids. DATA COLLECTION AND ANALYSIS: Two authors independently extracted data, assessed risk of bias, and assessed the quality of the evidence using the GRADE approach. MAIN RESULTS: This updated review included four studies with 221 women with uterine fibroids. The evidence was very low quality, downgraded for serious risk of bias, due to poor reporting of study methods, and serious imprecision. Levonorgestrel-releasing intrauterine device (LNG-IUS) versus hysterectomy There was no information on the outcomes of interest, including adverse events. LNG-IUS versus low dose combined oral contraceptive (COC) At 12 months, we are uncertain whether LNG-IUS reduced the percentage of abnormal uterine bleeding, measured with the alkaline hematin test (mean difference (MD) 77.50%, 95% confidence interval (CI) 70.44 to 84.56; 1 RCT, 44 women; very low-quality evidence), or the pictorial blood assessment chart (PBAC; MD 34.50%, 95% CI 11.59 to 57.41; 1 RCT, 44 women; very low-quality evidence); increased haemoglobin levels (MD 1.50 g/dL, 95% CI 0.85 to 2.15; 1 RCT, 44 women; very low-quality evidence), or reduced fibroid size more than COC (MD 1.90%, 95% CI -12.24 to 16.04; 1 RCT, 44 women; very low-quality evidence). The study did not measure adverse events. LNG-IUS versus oral progestogen (norethisterone acetate (NETA)) Compared to NETA, we are uncertain whether LNG-IUS reduced abnormal uterine bleeding more from baseline to six months (visual bleeding score; MD 23.75 points, 95% CI 1.26 to 46.24; 1 RCT, 45 women; very low-quality evidence); increased the percentage of change in haemoglobin from baseline to three months (MD 4.53%, 95% CI 1.46 to 7.60; 1 RCT, 48 women; very low-quality evidence), or from baseline to six months (MD 10.14%, 95% CI 5.57 to 14.71; 1 RCT, 45 women; very low-quality evidence). The study did not measure fibroid size. Spotting (adverse event) was more likely to be reported by women with the LNG-IUS (64.3%) than by those taking NETA (30%; 1 RCT, 45 women; very low-quality evidence). Oral progestogen (dienogest, desogestrel) versus goserelin acetate Compared to goserelin acetate, we are uncertain whether abnormal uterine bleeding was reduced at 12 weeks with dienogest (PBAC; MD 216.00 points, 95% CI 149.35 to 282.65; 1 RCT, 14 women; very low-quality evidence) or desogestrel (PBAC; MD 78.00 points, 95% CI 28.94 to 127.06; 1 RCT, 16 women; very low-quality evidence). Vasomotor symptoms (adverse events, e.g. hot flashes) are only associated with goserelin acetate (55%), not with dienogest (1 RCT, 14 women; very low-quality evidence) or with desogestrel (1 RCT, 16 women; very low-quality evidence). The study did not report fibroid size. AUTHORS' CONCLUSIONS: Because of very low-quality evidence, we are uncertain whether the LNG-IUS reduces abnormal uterine bleeding or increases haemoglobin levels in premenopausal women with uterine fibroids, compared to COC or norethisterone acetate. There was insufficient evidence to determine whether the LNG-IUS reduces the size of uterine fibroids compared to COC. We are uncertain whether oral progestogens reduce abnormal uterine bleeding as effectively as goserelin acetate, but women reported fewer adverse events, such as hot flashes.

Extended-cycle versus conventional treatment with a combined oral contraceptive containing ethinylestradiol (30 µg) and levonorgestrel (150 µg) in a randomized controlled trial.

The objective was to assess efficacy and safety of a combined oral contraceptive containing ethinylestradiol (EE) and levonorgestrel (LNG) in an extended-cycle vs. a conventional-cycle regimen. This first European randomized, active controlled, open, prospective, parallel-group trial was conducted in 48 German gynecological centers. 1,314 healthy, sexually active women aged 18-35 years were randomized. With an unadjusted PI of 0.483 (upper 95% CI: 1.237), the extended-cycle regimen fulfilled the contraceptive efficacy of EE/LNG, the requirements of the European Medicines Agency. The mean total number of bleeding days per year was significantly lower in the extended-cycle vs. the conventional-cycle regimen. Analyses of bleeding patterns showed a reduced total number of bleeding/spotting days per year in the extended-cycle vs. the conventional-cycle regimen. Cycle-associated complaints and AE were comparable in both groups. Both regimens were very well accepted. The extended-cycle regimen of EE/LNG was effective and well tolerated resulting in a lower number of bleeding days and a favorable bleeding pattern compared to the conventional-cycle regimen.

Triclosan and Female Reproductive Health: A Preconceptional Cohort Study.

BACKGROUND: Triclosan (2,4,4'-trichloro-2'-hydroxy-diphenyl ether) is widely used in personal care and household products. Previous in vitro and in vivo studies showed that triclosan may affect female reproductive health. However, evidence from human studies is scarce. OBJECTIVES: To assess the potential effects of triclosan on women's reproductive health. METHODS: A prospective cohort study recruited 1,182 couples who planned to conceive and presented to preconception care clinics for physical examination in Shanghai, China, between 2013 and 2015. These couples were then prospectively followed every 2 months for 12 months. Triclosan was quantified in preconception urine samples at enrollment. The outcomes of interest included menstruation and fecundity. Normal menstruation was defined as a woman who had normal cycle duration between 21 and 35 days, duration of menstrual bleeding between 3 and 7 days, and self-reported normal amount of menstrual bleeding. RESULTS: A total of 698 women were included in the analysis on the association between triclosan and menstruation. Compared with low triclosan levels, high triclosan levels were associated with increased risks of abnormal menstruation [adjusted odds ratio (OR) = 1.47; 95% confidence interval = 1.05, 2.06] and prolonged menstrual cycle (OR = 2.08; 95% confidence interval = 1.00, 2.31). In the analysis on the association between triclosan and fecundability, 648 women were included. Compared with the lowest tertile of triclosan level (<1.1 ng/mL), the highest level (>4.5 ng/mL) was associated with a 23% of reduction in fecundability and there tended to be a dose-response pattern. CONCLUSION: Our findings suggest that triclosan may affect menstruation and reduce female fecundity.

Adjuvant gonadotropin-releasing hormone analogues for the prevention of chemotherapy-induced premature ovarian failure in premenopausal women.

BACKGROUND: This is an update of the original review published in the Cochrane Database of Systematic Reviews 2011, Issue 11, and updated in 2015, Issue 4.Chemotherapy has significantly improved prognosis for women with malignant and some non-malignant conditions. This treatment, however, is associated with ovarian toxicity. The use of gonadotropin-releasing hormone (GnRH) analogues, both agonists and antagonists, may have a protective effect on the ovaries. The primary mechanism of action of GnRH analogues is to suppress the gonadotropin levels to simulate pre-pubertal hormonal milieu and subsequently prevent primordial follicles from maturation and therefore decrease the number of follicles that are more vulnerable to chemotherapy. OBJECTIVES: To assess the efficacy and safety of GnRH analogues given before or in parallel to chemotherapy to prevent chemotherapy-related ovarian damage in premenopausal women with malignant or non-malignant conditions. SEARCH METHODS: The search was run for the original review in July 2011, and for the first update in July 2014. For this update we searched the following databases in November 2018: the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, and the Chinese Biomedicine Database (CBM). SELECTION CRITERIA: Randomised controlled trials (RCTs), in all languages, which examined the effect of GnRH analogues for chemotherapy-induced ovarian failure in premenopausal women, were eligible for inclusion in the review. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed trial quality using the Cochrane 'Risk of bias' tool. We analysed binary data using risk ratios (RRs) with 95% confidence intervals (CI) and for continuous data, we used the standardized mean difference (SMD) to combine trials. We applied the random-effects model in our analyses. We used the GRADE approach to produce a 'Summary of findings' table for our main outcomes of interest. MAIN RESULTS: We included 12 RCTs involving 1369 women between the ages of 12 and 51.1 years. Participants were diagnosed with breast malignancy, ovarian malignancy, or Hodgkin's lymphoma, and most of them received alkylating, or platinum complexes, based chemotherapy. The included studies were funded by a university (n = 1), research centres (n = 4), and pharmaceutical companies (n = 1). Trials were at high or unclear risk of bias.Comparison 1: GnRH agonist plus chemotherapy versus chemotherapy aloneThe incidence of menstruation recovery or maintenance was 178 of 239 (74.5%) in the GnRH agonist group and 110 of 221 (50.0%) in the control group during a follow-up period no longer than 12 months (RR 1.60, 95% CI 1.14 to 2.24; 5 studies, 460 participants; I2 = 79%; low-certainty evidence), with an overall effect favouring treatment with GnRH agonist (P = 0.006). However, we observed no difference during a follow-up period longer than 12 months between these two groups (P = 0.24). In the GnRH agonist group, 326 of 447 participants had menstruation recovery or maintenance (72.9%) in comparison to the control group, in which 276 of 422 participants had menstruation recovery or maintenance (65.4%) during a follow-up period longer than 12 months (RR 1.08, 95% CI 0.95 to 1.22; 8 studies, 869 participants; I2 = 56%; low-certainty evidence).The incidence of premature ovarian failure was 43 of 401 (10.7%) in the GnRH agonist group and 96 of 379 (25.3%) in the control group (RR 0.44, 95% CI 0.31 to 0.61; 4 studies, 780 participants; I2 = 0%; moderate-certainty evidence), with an overall effect favouring treatment with GnRH agonist (P < 0.00001).The incidence of pregnancy was 32 of 356 (9.0%) in the GnRH agonist group and 22 of 347 (6.3%) in the control group (RR 1.59, 95% CI 0.93 to 2.70; 7 studies, 703 participants; I2 = 0%; low-certainty evidence), with no difference between groups (P = 0.09). However, we are cautious about this conclusion because there were insufficient data about whether the participants intended to become pregnant.The incidence of ovulation was 29 of 47 (61.7%) in the GnRH agonist group and 12 of 48 (25.0%) in the control group (RR 2.47, 95% CI 1.43 to 4.26; 2 studies, 95 participants; I2 = 0%; low-certainty evidence) with an overall effect favouring treatment with GnRH (P = 0.001).The most common adverse effects of GnRH analogues included hot flushes, vaginal dryness, urogenital symptoms, and mood swings. The pooled analysis of safety data showed no difference in adverse effects between GnRH agonist group and control group.Comparison 2: GnRH agonist-antagonist cotreatment plus chemotherapy versus chemotherapy aloneOnly one RCT discussed GnRH agonist-antagonist cotreatment. The limited evidence showed the incidence of menstruation recovery or maintenance was 20 of 25 (80%) in both cotreatment group and control group during a 12-month follow-up period (RR 1.00, 95% CI 0.76 to 1.32; 50 participants; very low-certainty evidence), with no difference between groups (P = 1.00). In the cotreatment group, 13 of 25 participants had menstruation recovery or maintenance (52.0%) in comparison to the control group, in which 14 of 25 participants had menstruation recovery or maintenance (56.0%) during a follow-up period longer than 12 months (RR 0.93, 95% CI 0.56 to 1.55; 50 participants; very low-certainty evidence), with no difference between groups (P = 0.78). The incidence of pregnancy was 1 of 25 (4.0%) in the cotreatment group and 0 of 25 (0%) in the control group (RR 3.00, 95% CI 0.13 to 70.30; 50 participants; very low-certainty evidence), with no difference between groups (P = 0.49). AUTHORS' CONCLUSIONS: GnRH agonist appears to be effective in protecting the ovaries during chemotherapy, in terms of maintenance and resumption of menstruation, treatment-related premature ovarian failure and ovulation. Evidence for protection of fertility was insufficient and needs further investigation. Evidence was also insufficient to assess the effect of GnRH agonist and GnRH antagonist cotreatment on ovarian protection against chemotherapy. The included studies differed in some important aspects of design, and most of these studies had no age-determined subgroup analysis. Large and well-designed RCTs with longer follow-up duration should be conducted to clarify the effects of GnRH analogues in preventing chemotherapy-induced ovarian failure, especially on different age groups or different chemotherapy regimens. Furthermore, studies should address the effects on pregnancy rates and anti-tumour therapy.

Norethindrone is superior to combined oral contraceptive pills in short-term delay of menses and onset of breakthrough bleeding: a randomized trial.

BACKGROUND: To determine whether oral norethindrone acetate is superior to combined oral contraceptives (OCP) in delaying menstruation and preventing breakthrough bleeding when started late in the cycle. METHODS: This article comprises of a case control study followed by a pilot randomized controlled study. In the first study, four women who presented late in their cycle and desired avoiding vaginal bleeding within 10 days before a wedding were started on norethindrone 5 mg three times daily and compared to age matched controls started on OCPs. Subsequently, a randomized controlled pilot study (n = 50) comparing OCPs to norethindrone for the retiming of menses was conducted. Percentage of women reporting spotting were compared with level of statistical significance set at p < 0.05. RESULTS: Of the norethindrone treated group, only 2 women (8%) reported spotting compared with 10 women (43%) in the control group (p < 0.01). Norethindrone recipients experienced significant weight gain, which resolved after cessation of therapy and had heavier withdrawal bleed (p < 0.04) when compared to controls. Patient satisfaction was significantly higher in the norethindrone group, with 80% willing to choose this method again. Time to conceive was significantly shorter in the norethindrone group (p < 0.03). CONCLUSIONS: Norethindrone, begun on or before cycle day 12, is superior for women who desire to avoid breakthrough bleeding and maintain fertility when compared to OCPs. It is an ideal approach in patients presenting late in their cycle and who desire delaying menses as well as in circumstances when even minute amounts of breakthrough bleeding cannot be tolerated. TRIAL REGISTRATION: Clinicaltrials.gov NCT03594604 , July 2018. Retrospectively registered.

Hormonal oral contraceptive influence on isolation, Characterization and cryopreservation of mesenchymal stem cells from menstrual fluid.

The purpose of the study was to evaluate whether the intake of hormonal oral contraceptive influences the viability of mesenchymal stem cell. Sixteen healthy female volunteers with regular menstrual cycles were invited to participate. Menstrual fluid was collected on the day of maximum flux, and collected cells were analyzed by a 'minimal standard' for MSC characterization: plastic adherence, trilineage (adipogenic, osteogenic, chondrogenic) in vitro differentiation and a minimalistic panel of markers assessed by flow cytometry (CD731, CD901, CD1051, CD34-, CD45-) using monoclonal antibodies. The participants were divided into two groups: Group 1 - no hormonal contraceptive use; Group 2 - hormonal oral contraceptive use. The median of the menstrual fluid volume was 5.0 and the median number of cells was 5.2 × 106. Median of cell viability was 89.3%. After culture, mesenchymal stem cells increased from 0.031% of the total cells to 96.9%. The cells formed clusters and reached confluence after 15-21 days of culture in the first passage. In the second passage, clusters and the confluence were observed after 3 days of culture. No difference was observed between the groups. Our data suggest that oral hormonal contraceptive intake maintains the viability of mesenchymal stem cells from menstrual fluid.

Effect of alpha-lipoic acid at the combination with mefenamic acid in girls with primary dysmenorrhea: randomized, double-blind, placebo-controlled clinical trial.

Primary dysmenorrhea is a common gynecologic disorder and is one of the main causes for referral to the gynecology clinic. This study aimed to determine the effects of alpha-lipoic acid (ALA) and mefenamic acid and a combination compared with placebo on the girls with primary dysmenorrhea. This double-blind, placebo-controlled clinical trial done on population consisted of female students living in dormitories of Qazvin University of Medical Sciences who had moderate to severe dysmenorrhea using the Visual Analog Scale (VAS) questionnaire. Participants were randomly divided into four groups (n = 100): ALA, mefenamic acid, ALA + mefenamic acid and placebo groups. ALA and mefenamic acid were administrated in 600 mg and 250 mg, respectively. The severity of the pain was measured in the beginning and the end of the study. Statistical analysis was performed using SPSS software (SPSS Inc., Chicago, IL). Our final results suggested that, although mefenamic acid significantly decreased the menstrual pain, ALA supplementation, 600 mg, would be more efficient than mefenamic acid in 250 mg. Also, the combination of ALA and mefenamic acid significantly has been far. Considering the ALA supplementation effect on pain relief in patients with primary dysmenorrhea, this antioxidant can be recommended for the healing of symptoms of these patients.

Prediction of ovarian function recovery in young breast cancer patients after protection with gonadotropin-releasing hormone agonist during chemotherapy.

PURPOSE: This study evaluated predictive factors for recovery of ovarian function after ovarian protection by GnRH agonist during chemotherapy in young breast cancer patients. METHODS: This prospective cohort study analyzed 105 young breast cancer patients who were studied longitudinally after receiving GnRH agonist during cyclophosphamide-based chemotherapy for ovarian protection. Associations between pretreatment hormones, clinical factors, and recovery of ovarian function (resumption of menstruation or anti-Müllerian hormone (AMH) ≥ 1 ng/ml) were evaluated at 12 months and long-term follow-up after completion of chemotherapy. RESULTS: Mean age was 32 years (range 23-42 years). In multivariate analyses, tamoxifen use (P = 0.035) and pretreatment follicle-stimulating hormone (FSH) (P = 0.032) were predictive of resumption of menstruation, and age (P = 0.019), tamoxifen use (P = 0.022), pretreatment FSH (P < 0.001), and AMH (P = 0.040) were predictors for AMH ≥ 1 ng/ml at 12 months. In addition, pretreatment AMH was a predictor for AMH ≥ 1 ng/ml after long-term follow-up. Receiver operating characteristic curve analyses gave area under the curve of 0.805 for resumption of menstruation and 0.903 for serum AMH concentration ≥ 1 ng/ml at 12 months, when age, tamoxifen use, pretreatment FSH, and AMH were combined. CONCLUSION: Pretreatment AMH (3.26 ng/ml), age (33.9 years), pretreatment FSH (5.5 IU/l), and tamoxifen use are useful predictors for AMH ≥ 1 ng/ml at 12 months after GnRH agonist. This finding will support patient and clinician decision-making regarding fertility preservation.

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.

There might be blood: a scoping review on women's responses to contraceptive-induced menstrual bleeding changes.

INTRODUCTION: Concern about side effects and health issues are common reasons for contraceptive non-use or discontinuation. Contraceptive-induced menstrual bleeding changes (CIMBCs) are linked to these concerns. Research on women's responses to CIMBCs has not been mapped or summarized in a systematic scoping review. METHODS: We conducted a systematic scoping review of data on women's responses to CIMBCs in peer-reviewed, English-language publications in the last 15 years. Investigator dyads abstracted information from relevant studies on pre-specified and emergent themes using a standardized form. We held an expert consultation to obtain critical input. We provide recommendations for researchers, contraceptive counselors, and product developers. RESULTS: We identified 100 relevant studies. All world regions were represented (except Antarctica), including Africa (11%), the Americas (32%), Asia (7%), Europe (20%), and Oceania (6%). We summarize findings pertinent to five thematic areas: women's responses to contraceptive-induced non-standard bleeding patterns; CIMBCs influence on non-use, dissatisfaction or discontinuation; conceptual linkages between CIMBCs and health; women's responses to menstrual suppression; and other emergent themes. Women's preferences for non-monthly bleeding patterns ranged widely, though amenorrhea appears most acceptable in the Americas and Europe. Multiple studies reported CIMBCs as top reasons for contraceptive dissatisfaction and discontinuation; others suggested disruption of regular bleeding patterns was associated with non-use. CIMBCs in some contexts were perceived as linked with a wide range of health concerns; e.g., some women perceived amenorrhea to cause a buildup of "dirty" or "blocked" blood, in turn perceived as causing blood clots, fibroids, emotional disturbances, weight gain, infertility, or death. Multiple studies addressed how CIMBCs (or menstruation) impacted daily activities, including participation in domestic, work, school, sports, or religious life; sexual or emotional relationships; and other domains. CONCLUSIONS: Substantial variability exists around how women respond to CIMBCs; these responses are shaped by individual and social influences. Despite variation in responses across contexts and sub-populations, CIMBCs can impact multiple aspects of women's lives. Women's responses to CIMBCs should be recognized as a key issue in contraceptive research, counseling, and product development, but may be underappreciated, despite likely - and potentially substantial - impacts on contraceptive discontinuation and unmet need for modern contraception.

Two Years Follow-Up of Patients with Abnormal Uterine Bleeding after Insertion of the Levonorgestrel-Releasing Intrauterine System.

AIM: To evaluate the efficacy and safety of levonorgestrel-releasing intrauterine system (LNG-IUS) in the long-term treatment of heavy menstrual blood loss in women unrelated to intrauterine pathology. METHODS: One hundred and six parous women aged 33-48 years with recurrent heavy menstrual bleeding (HMB) participated in this study. The women were followed up for 24 months and were assessed for intensity of bleeding both for pre- and post-insertion periods. An LNG-IUS was inserted in each patient within 7 days of the start of menstrual flow. The women were followed up at 1, 3, 6, 12, 18, and 24 months following the insertion of the intrauterine device. RESULTS: One hundred and two women completed the follow-up period and had a significant reduction in the amount of menstrual blood loss. The LNG-IUS was well tolerated by all women. Pre-treatment of the use of the LNG-IUS, endometrial biopsy patterns for irregular proliferative endometrium and for atypical simple hyperplasia were 34/106 (32.08%) and 61/106 (57.55%) respectively and after treatment no abnormal pathologic findings were determined (p < 0.001). CONCLUSION: Our findings indicate that the LNG-IUS is effective for significantly reducing the amount of menstrual blood loss in women with HMB.

Health-related quality of life in young women starting hormonal contraception: a pilot study.

OBJECTIVES: Our purpose was to study whether there is a difference in self-rated health-related quality of life (HRQOL) and changes in HRQOL perception after 3 months of hormonal contraceptive use in adolescents. Seasonal variations in symptoms of depression were also studied. METHODS: A test group (T1) (n = 193) and a selected control group (n = 238) of women aged 14-20 years who were visiting a young person's clinic completed the 36-item short-form health survey (SF-36) and answered additional questions on menstrual history and pattern, need for menstrual pain relief medication, and other regular medication. The test group was reassessed after 3 months of hormonal contraception (T2). Seasonal variations in reported SF-36 scores were studied for the whole group. RESULTS: The selected control group and test group at T1 were similar with regard to age at menarche and menstrual pattern. The duration of bleeding and use of painkillers were significantly reduced and the impact on everyday life was significantly improved after 3 months of hormonal contraception (p = .000, two-tailed). No changes in HRQOL or symptoms of possible depression were found after 3 months of hormonal contraception. The highest prevalence odds ratio for possible depression (SF-36 mental health scale score ≤48), adjusted for group, season and age, for spring vs winter, was 2.15 (95% confidence interval 0.95, 4.85). CONCLUSIONS: After 3 months of hormonal contraception both the number of days of menstrual bleeding and the use of medication to relieve menstrual pain were reduced, but there were no significant changes in self-rated HRQOL perception. Seasonal effects on HRQOL were reported.

Influence of age on tolerability, safety and effectiveness of subdermal contraceptive implants.

The use of long-acting contraceptive methods is on the rise. The aim of this study was to describe the main variables (effectiveness, tolerability, menstrual bleeding) associated with the use of subdermal contraceptive implants and to investigate the influence of age on these variables. This was a descriptive, retrospective, observational study of 221 cases of contraceptive implants inserted at a Spanish hospital between 2006 and 2015. The mean age of implant users was 31.2 ± 7.5 years. Effectiveness was 100% and good tolerability was recorded for 86.5%. Infrequent bleeding was the most common bleeding pattern, followed by amenorrhoea. Of the 221 implants inserted, 47.5% were removed. The main reasons were expiration (54.3%) and discomfort due to bleeding alterations and other adverse effects (25.7%). Nulliparity and weight gain were significantly associated with an increased probability of implant removal. This study shows that implants were highly effective, safe and well-tolerated in our population. The age of users had no influence on any of the study variables analysed. Impact Statement What is already known on this subject? Subdermal contraceptive implants are long-acting reversible contraceptives which are both safe and effective. What do the results of this study add? The age of users had no influence on any of the study variables analysed. Nulliparity and weight gain were significantly associated with an increased probability of implant removal. What are the implications of these findings for clinical practice and/or further research? Subdermal contraceptive implants were a safe and effective long-acting progestin contraceptive method for women from all age groups in our series because no significant age-related differences were observed for the tolerability, vaginal bleeding patterns, the effectiveness, the adverse effects or any other variables.

Observation of clinical efficacy of yousiyue for endometrium regeneration after superconducting visual abortion and its nursing.

Present study is carried out to observe and analyze the curative effect of Yousiyue (Drospirenone and Ethinylestradiol tablets) on endometrium regeneration after superconducting visual abortion and explore the nursing mode. A total of 150 patients who underwent superconducting visual abortion in our hospital were enrolled and divided into study and reference groups with 75 patients each according to random grouping. Both groups were treated with vaginal ultrasonography-mediated abortion. The study group was treated with Yousiyue after the operation plus comprehensive nursing intervention program. The reference group only received general routine nursing and treatment. The treatment outcomes of the two groups were compared. Comparison of endometrial thickness, menses return time and menstrual reduction rate reveals significant advantage of study group over reference group, p<0.05; study group has an overall satisfaction significantly higher than the reference group, p<0.05. The implementation of Yousiyue in endometrium regeneration after superconducting visual abortion can receive good results, which is worthy of popularization and application.