Human Menstrual Blood-Derived Stem Cells Protect against Tacrolimus-Induced Islet Dysfunction via Cystathionine ß-Synthase Mediated IL-6/STAT3 Inactivation.

Diabetes imposes a huge burden worldwide. Islet transplantation is an alternative therapy for diabetes. However, tacrolimus, a kind of immunosuppressant after organ transplantation, is closely related to post-transplant diabetes mellitus. Mesenchymal stem cells (MSCs) have attracted interest for their potential to alleviate diabetes. In vivo experiments revealed that human menstrual blood-derived stem cells (MenSCs) treatment improved tacrolimus-induced blood glucose, body weight, and glucose tolerance disorders in mice. RNA sequencing was used to analyze the potential therapeutic targets of MenSCs. In this study, we illustrated that cystathionine ß-synthase (CBS) contributed to tacrolimus -induced islet dysfunction. Using ß-cell lines (MIN6, ß-TC-6), we demonstrated that MenSCs ameliorated tacrolimus-induced islet dysfunction in vitro. Moreover, MenSC reduced the tacrolimus-induced elevation of CBS levels and significantly enhanced the viability, anti-apoptotic ability, glucose-stimulated insulin secretion (GSIS), and glycolytic flux of ß-cells. We further revealed that MenSCs exerted their therapeutic effects by inhibiting CBS expression to activate the IL6/JAK2/STAT3 pathway. In conclusion, we showed that MenSCs may be a potential strategy to improve tacrolimus-induced islet dysfunction.

Timing of onset of menses after GnRH agonist treatment for central precocious puberty.

OBJECTIVES: To understand possible predictors of the onset of menses after gonadotropin-releasing hormone agonist treatment cessation in girls with central precocious puberty (CPP). METHODS: This exploratory post hoc analysis of a phase 3 and 4 trial of girls with CPP treated with once-monthly intramuscular leuprolide acetate examined onset of menses after treatment completion using a time-to-event analysis. Pretreatment and end-of-treatment chronologic age (CA), bone age (BA)/CA ratio, and Tanner breast stage; pretreatment menses status; and end-of-treatment BA and body mass index (BMI) were studied as potential factors influencing the onset of menses. RESULTS: Median time to first menses after stopping treatment was 18.3 months among 35 girls (mean age at onset of treatment, 6.8 years) examined. Of 26 girls experiencing menses, 11 (42 %) menstruated at 16-21 months after stopping treatment. Most girls with pretreatment BA/CA≥1.4 started menstruating very close to 18 months after stopping treatment; those with less advanced BA/CA experienced menses at 9-18 months. End-of-treatment BA/CA≥1.2 was associated with a quicker onset of menses (14.5 vs. 18.5 months for BA/CA<1.2, p=0.006). End-of-treatment BA≥12 years predicted longer time to menses. No relationship with time to menses was observed for pretreatment menarche status, pretreatment or end-of-treatment Tanner breast stage (<3/≥3) or CA (<6/≥6 or ≤11/>11), or end-of-treatment BMI percentiles (<85.6/≥85.6 and <92.6/≥92.6). CONCLUSIONS: Pretreatment menarche status or CA do not appear to predict onset of menses, but pre- and end-of-treatment BA/CA may be helpful in anticipating time to first menses after stopping treatment.

The effectiveness of desogestrel for endometrial protection in women with abnormal uterine bleeding-ovulatory dysfunction: a non-inferiority randomized controlled trial.

Women with chronic abnormal uterine bleeding-ovulatory dysfunction (AUB-O) are at increased risk of endometrial neoplasia. We conducted a non-inferiority randomized controlled trial to determine the effectiveness of two cyclic-progestin regimens orally administered 10 d/month for 6 months on endometrial protection and menstruation normalization in women with AUB-O. There were 104 premenopausal women with AUB-O randomized to desogestrel (DSG 150 µg/d, n = 50) or medroxyprogesterone acetate (MPA 10 mg/d, n = 54) group. Both groups were comparable in age (44.8 ± 5.7 vs. 42.5 ± 7.1 years), body mass index (24.8 ± 4.7 vs. 24.9 ± 4.7 kg/m2), and AUB characteristics (100% irregular periods). The primary outcome was endometrial response rate (the proportion of patients having complete pseudodecidualization in endometrial biopsies during treatment cycle-1). The secondary outcome was clinical response rate (the proportion of progestin withdrawal bleeding episodes with acceptable bleeding characteristics during treatment cycle-2 to cycle-6). DSG was not inferior to MPA regarding the endometrial protection (endometrial response rate of 78.0% vs. 70.4%, 95% CI of difference - 9.1-24.4%, non-inferiority limit of - 10%), but it was less effective regarding the menstruation normalization (acceptable bleeding rate of 90.0% vs 96.6%, P = 0.016).Clinical trial registration: ClinicalTrials.gov (NCT02103764, date of approval 18 Feb 2014).

Post-treatment anti-Mullerian hormone (AMH) levels predict long-term ovarian dysfunction in women with hematological malignancies.

Fertility is a concern in young female survivors of hematological malignancies. We evaluated post-treatment ovarian function in patients by measuring anti-Müllerian hormone (AMH) and conventional hormone levels to correlate with menstruation and fertility.The prospective cohort study included 29 reproductive-aged women diagnosed with Hodgkin lymphoma (n = 11), non-Hodgkin lymphoma (n = 9) or acute myeloid leukemia (n = 9). Hormone assays were measured after treatment was completed and compared to age-matched healthy controls. Menstrual changes and postmenopausal symptoms were assessed annually.Serum AMH levels were significantly lower compared to controls at 12 months after treatment [1.0 (0.18-1.8) vs. 2.2 (1.8-4.8) ng/mL; P < .001). At 12 months, FSH and LH levels were significantly higher compared to controls. The interruption of menstrual cycles was observed in 80% (22/27) of patients. Normal menstruation returned at a median of 1.5 months after cessation of treatment in 71% of patients, while 29% of patients had persistent amenorrhea. Low AMH levels at 12 months after therapy (<1 ng/mL) correlated more strongly with abnormal menstrual cycles than normal AMH levels (46% vs. 0%, P = .04). Four patients with low AMH consulted an infertility clinic.In summary, low serum AMH at 12 months after chemotherapy was associated with persistent menstrual abnormalities.

Five-year changes in ovarian function restoration in premenopausal patients with breast cancer taking tamoxifen after chemotherapy: An ASTRRA study report.

BACKGROUND: Adding ovarian function suppression (OFS) after chemotherapy improves survival in young women with moderate- and high-risk breast cancer. Assessment of ovarian function restoration after chemotherapy becomes critical for subsequent endocrine treatment and addressing fertility issues. PATIENTS AND METHODS: In the adding OFS after chemotherapy trial, patients who resumed ovarian function up to 2 years after chemotherapy were randomised to receive either 5 years of tamoxifen or adding 2 years of OFS with tamoxifen. Ovarian function was evaluated from enrolment to randomisation, and patients who did not randomise because of amenorrhoea for 2 years received tamoxifen and were followed up for 5 years. Prospectively collected consecutive hormone levels (proportion of patients with premenopausal follicle-stimulating hormone [FSH] levels <30 mIU/mL and oestradiol [E2] levels ≥40 pg/mL) and history of menstruation were available for 1067 patients with breast cancer. RESULTS: Over 5 years of tamoxifen treatment, 69% of patients resumed menstruation and 98% and 74% of patients satisfied predefined ovarian function restoration as per serum FSH and E2 levels, respectively. Menstruation was restored in 91% of patients younger than 35 years at baseline, but in only 33% of 45-year-old patients over 5 years. Among these patients, 41% experienced menstruation restoration within 2 years after chemotherapy and 28% slowly restored menstruation after 2-5 years. Younger age (<35 years) at baseline, anthracycline without taxanes and ≤90 days of chemotherapy were predictors of menstruation restoration. CONCLUSIONS: During 5 years of tamoxifen treatment after chemotherapy, two-thirds of the patients experienced menstruation restoration, especially patients younger than 35 years. Young age, Adriamycin without taxanes and short duration of chemotherapy appeared to have a positive effect on ovarian reserves in the long term. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00912548.

Does menstruation-related headache occur exclusively in women with migraine?

To determine the relation between headache and menstruation in women with migraine and the use of estrogen by these women. This was a prospective, cross-sectional, observational study with group comparison, using non-random sample and convenience. We interviewed 79 women diagnosed with migraine or tension-type headache (TTH), according to the ICHD-3, regarding the relation between headache and menstruation. Of the 79 women with headache, 60 (76%) had migraine and 19 (24%) had episodic TTH. The most frequent subtype of migraine was without aura (54/60, 90%). The age ranged from 18 to 42 years, with an average of 22.6 ± 4.1 years. Migraine affected women aged 22.4 ± 3.6 years, whereas in TTH, the age was 23.0 ± 5.4 years. Menstruation-related headache occurred in 41.9% of women with migraine and in only 6.3% of those with TTH. These differences were significant (χ2 = 5.2; p = 0.022). Of the five women diagnosed with migraine with aura, two used estrogen. Menstruation-related headache predominates in women with migraine and often women with migraine with aura use estrogen.

Options for Prevention and Management of Menstrual Bleeding in Adolescent Patients Undergoing Cancer Treatment: ACOG Committee Opinion, Number 817.

ABSTRACT: Obstetrician-gynecologists frequently are consulted either before the initiation of cancer treatment to request menstrual suppression or during an episode of severe heavy bleeding to stop bleeding emergently. Adolescents presenting emergently with severe uterine bleeding usually require only medical management; surgical management rarely is required. Surgical management should be considered for patients who are not clinically stable, or for those whose conditions are not suitable for medical management or have failed to respond appropriately to medical management. When used continuously, combined hormonal contraceptives are effective for producing amenorrhea, although complete amenorrhea cannot be guaranteed. The risk of venous thromboembolism in patients with cancer is compounded by multiple factors, including presence of metastatic or fast-growing, biologically aggressive cancers; hematologic cancers; treatment-related factors such as surgery or central venous catheters; and the number and type of comorbid conditions. Although as a group, patients undergoing cancer treatment are at elevated risk of venous thromboembolism compared with the general population, this risk may be extremely elevated for certain patients and existing guidance on risk stratification should be consulted. The decision to use estrogen in patients with cancer should be tailored to the individual patient after collaborative consideration of the risk-benefit ratio with the patient and the health care team; the patient should be closely monitored for known adverse effects such as liver toxicity and venous thromboembolism.

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.

Relugolix for the treatment of uterine fibroids.

INTRODUCTION: Uterine fibroids (UF) are benign tumors common in premenopausal women, with strong impact on the health-care systems. For many years, surgery represented the only therapy for symptomatic fibroids. However, clinicians are observing a switch from surgery to noninvasive methods; in particular, medical treatment has been shown to be efficacious in obtaining a bleeding reduction and in ameliorating patient conditions. AREAS COVERED: The authors review the current options available for the treatment of women with UF, with a special focus on the newest one, relugolix. It is an orally active non-peptide Gonadotropin-releasing hormone (GnRH)-receptor antagonist recently licensed for women with symptomatic fibroids. Relugolix is a well-tolerated safe drug; it is effective in inducing a dose-dependent decrease in menstrual blood loss, with faster reduction of heavy menstrual bleeding (HMB) and a greater shrinkage in fibroid volume compared to the current standard of GnRH agonist treatment. EXPERT OPINION: Relugolix is a promising drug for the non-surgical treatment of women with UF. To date, the only published data come from a well-selected Japanese female population study while results from worldwide ongoing studies are ongoing in order to confirm the efficacy of this GnRH agonist receptor.

Insulin Sensitizers for Improving the Endocrine and Metabolic Profile in Overweight Women With PCOS.

OBJECTIVE: To evaluate the efficacy of insulin sensitizers on menstrual frequency, sex hormone, and metabolic parameters in overweight women with polycystic ovary syndrome (PCOS). METHODS: We searched multiple databases from inception to September 2019 for randomized controlled trials. Network meta-analysis was conducted using multivariate random effects method. RESULTS: Fourteen trials reporting on 619 women were included. Compared with metformin, metformin + thiazolidinediones (TZDs) was more superior in menstrual recovery (weighted mean difference [WMD] 3.68; 95% credibility interval [CrI], 1.65 to 8.20), metformin +  glucagon-like peptide-1 (GLP-1) receptor agonists was more effective in decreasing androstenedione (WMD -2.53; 95% CrI, -3.96 to -1.09), both metformin + GLP-1 receptor agonists (WMD 9.22; 95% CrI, 5.46 to 12.98) and metformin + TZDs (WMD 4.30; 95% CrI, 0.78 to 7.82) were more effective in increasing sex hormone-binding globulin (SHBG), while TZDs were less effective in decreasing body mass index (BMI) (WMD 1.69; 95% CrI, 0.72 to 2.66). Compared with GLP-1 receptor agonists, metformin + GLP-1 receptor agonists was associated with higher SHBG (WMD 7.80; 95% CrI, 4.75 to 10.85), lower free testosterone (WMD -1.77; 95% CrI, -3.25 to -0.29), lower androstenedione (WMD -2.70; 95% CrI, -3.91 to -1.50) and lower fasting blood glucose (WMD -0.41; 95% CrI, -0.73 to -0.08). CONCLUSION: For overweight women with PCOS, both metformin combined with GLP-1 receptor agonists and metformin combined with TZDs appear superior to monotherapy in improving hyperandrogenemia. Metformin combined with TZDs could be particularly effective in promoting the recovery of menstruation. Metformin combined with GLP-1 receptor agonists has the additional advantage of improving fasting glucose when compared with GLP-1 receptor agonists alone. TZDs are inferior to metformin in decreasing BMI.

The impact of menstruation persistence or recovery after chemotherapy on survival in young patients with hormone receptor negative breast cancer.

INTRODUCTION: Hormone replacement therapy can diminish hormone depletion-related complaints in postmenopausal women, but is contraindicated for postmenopausal breast cancer (BC) patients. Recovery of menstruation after chemotherapy-induced amenorrhea in young hormone receptor-negative BC patients however, is accepted. To determine the safety of this strategy, we investigated the effect of recovery of menstruation on disease-free survival (DFS) and overall survival (OS) in young hormone receptor-negative BC patients treated with (neo)adjuvant chemotherapy. METHODS: We selected 636 patients from a single-center cohort with early stage hormone receptor-negative BC and under the age of 50 years when treated with chemotherapy. Sufficient data on course of menstruation in medical records was retrospectively found for 397 patients, of whom 299 patients (75%) had a recovery of menstruation after chemotherapy. We used Cox proportional hazards models to estimate hazard ratios (HR) for the effect of recovery of menstruation on DFS and OS. RESULTS: Patients with recovery of menstruation after chemotherapy less frequently had lymph node involvement at diagnosis (45% vs 66%, p = 0.001). After a median follow-up of 6.7 years, the adjusted hazard ratios were 1.45 (95% CI: 0.83-2.54) for DFS and 1.19 (95% CI: 0.71-1.98) for OS. CONCLUSION: No significantly increased recurrence risk was found for hormone receptor-negative BC patients with recovery of menstruation after chemotherapy. However, the outcome of the multivariable model is not reassuring and a potentially increased recurrence risk cannot be excluded. The results need to be validated in a larger prospective study for a more definitive answer.

Metformin intervention against ovarian toxicity during chemotherapy for early breast cancer: Study protocol for a randomized double-blind placebo-controlled trial.

BACKGROUND: With the significant improvement of the cure rate and survival rate of cancer patients, the survivors face quality-of-life problems, such as a significant decline in reproductive system development, ovarian reserves and function, and even fertility loss and early menopause. These problems are often highly associated with chemotherapy-induced ovarian damage in cancer treatment. However, there are no ideal treatment strategies at present. In our attempt to develop reagents and approaches for delaying ovarian aging and protecting chemotherapy-induced ovarian injury, we recently found that metformin may be the most promising drug to protect female malignant tumor patients from chemotherapy-induced ovarian injury. This trial aims to test whether administration of metformin during chemotherapy can protect the normal ovarian function of patients with early breast cancer. METHODS: This study is prospective, randomized, double-blind and placebo-controlled. Female patients with early breast cancer (N = 314) will be randomly assigned to two groups (placebo, metformin 2000 mg). Metformin will be administered during and after chemotherapy for patients with stage I-IIIa breast cancer. The primary outcome will be the menstruation recovery rate 12 months after chemotherapy, defined as recovery of menstruation twice in a row within 1 year. Patients will be followed up for 5 years to observe long-term ovarian function and prognosis, such as overall survival (OS), objective response rate (ORR), and disease-free survival (DFS). Quality of life and safety will also be assessed. DISCUSSION: Our research will provide a new treatment strategy for fertility protection, and clinical treatment guidance for cancer patients.

Feasibility and efficacy of gonadotropin-releasing hormone agonists for the prevention of chemotherapy-induced ovarian insufficiency in patients with malignant ovarian germ cell tumours (KGOG 3048R).

BACKGROUND: This study assessed the effects of gonadotropin-releasing hormone agonists (GnRHa) on the prevention of chemotherapy-induced ovarian insufficiency among young patients with malignant ovarian germ cell tumour (MOGCT) receiving chemotherapy. METHODS: This multicentre, retrospective study was conducted at 15 sites affiliated with the Korean Gynecologic Oncology Group and enrolled 354 patients between January 1995 and September 2018. Among them, 227 patients were included in this study and divided into two groups according to the use of GnRHa during chemotherapy (GnRHa versus no GnRHa groups). The primary objective was to compare the rates of menstrual resumption between the two groups. We also assessed the clinical determinants affecting menstrual resumption among the study groups. RESULTS: There were no significant differences between the GnRHa (n = 63) and no GnRHa (n = 164) groups regarding age at diagnosis, parity, ethnicity, age at menarche, body mass index, International Federation of Gynecology and Obstetrics stage, mode of surgery and surgery type. The rate of menstrual resumption after chemotherapy was 100% (63 of 63) in the GnRHa group and 90.9% (149 of 164) in the no GnRHa group (p = 0.013). The mean periods from last chemotherapy to menstrual resumption were 7.4 and 7.3 months in the GnRHa and no GnRHa groups, respectively. GnRHa co-administration during chemotherapy reduced the likelihood of amenorrhoea after chemotherapy, although statistical significance was not confirmed in the univariate analysis (odds ratio: 0.276; 95% confidence interval, 0.004-1.317; p = 0.077). CONCLUSION: Temporary ovarian suppression with GnRHa during chemotherapy does not significantly increase the chances of menstrual resumption in young patients with MOGCT.

Effect of Tahiti lime (Citrus latifolia) juice on the Production of the PGF2α/PGE2 and Pro-Inflammatory Cytokines involved in Menstruation.

Tahiti lemon juice (Citrus latifolia) (TLJ), as a natural source of flavonoids, has been used as an alternative to anti-inflammatory drugs for the treatment of dysmenorrhea and menstrual excessive bleeding, often associated with an imbalance of the prostaglandins (PG) levels. However, despite the positive effects, the mechanisms that rule menstruation control are still unknown. Therefore, the objectives were to characterize the TLJ and analyze its effect on the production of PGF2α, PGE2 and pro-inflammatory cytokines involved inmenstruation. Flavonoids from TLJ were discriminated by UPLC-DAD-MS/MS (Qq-TOF) and the effects of TLJ were studied in vitro by quantification of the contraction of myoblasts in culture and PGF2α and PGE2 productions. Further, the systemic and menstrual fluid levels of PGF2α, PGE2, IL-1ß, TNF-α, IL-6, AK1B1 and AK1C3 enzymes produced by women during the menstrual period were compared after exposition or not to TLJ or meloxicam. The results showed that TLJ induces an increase in the contraction of myoblasts and the PGF2α supernatant level. Regarding in vivo analysis, a higher concentration of PGF2α and an unaltered PGE2 level was also found in the menstrual blood of women treated with TLJ, in contrast with a lower level of PGE2 and PGF2α observed in the meloxicam group. Concerning cytokines, only menstrual TNF-α levels decrease after treatment with TLJ or meloxicam. In conclusion, TLJ may favor the control of menstruation events via a PGF2α mediated muscle contractile response.

Safety, influence on the endometrium, sonographic changes and bleeding profile after 13 cycles with the new drospirenone only pill (DOP) for contraception.

BACKGROUND: The primary objective of the present trial was to assess the endometrial safety of a new oral contraceptive containing 4 mg drospirenone for a total duration of 13 cycles of 28 days each: 24 days of active treatment followed by 4 days placebo treatment per treatment cycle. MATERIALS AND METHODS: This was a single-center, open-label, multiple-dose study on healthy female subjects at risk of pregnancy. Twenty one (= safety population set) pre-menopausal female Caucasian subjects started treatment with the study medication. The mean age was 29.0 years (range 19.0-36.0 years). Four subjects terminated the trial prematurely for the following reasons: on the subject's request (n=2), due to an adverse event (n=1) and due to loss of contact (n=1). Seventeen subjects completed the planned duration of 13 cycles of open treatment with the test product (each cycle of 28 days). RESULTS: At visit 1 (pre-treatment), the biopsy result in the safety population set was proliferative in 14 cases and secretory in seven cases. At visit 7, four cases showed an inadequate result (insufficient tissue for diagnosis), 12 as proliferative and three as secretory. The number of biopsies with proliferative and secretory results reduced under treatment (safety population). The pre-post treatment changes in the endometrial biopsy results in the treatment completers set (n=17) showed almost no differences. At visit 1 (pre-treatment), the biopsy result was proliferative in 12 cases and secretory in five cases. At visit 7 (after 13 cycles of 28 days), four cases showed an inadequate result (insufficient tissue for diagnosis), 11 as proliferative, and two as secretory. The mean endometrial thickness in the safety population was reduced from 8.3 mm at visit 1 to 6.0 mm at visit 7. When comparing the endometrial thickness in the 21 subjects (safety population), the endometrial thickness showed a pre-post difference of 2.1 mm, whereas the endometrial thickness in the 17 study completers showed a pre-post difference of 2.5 mm (8.2 mm at visit 1-5.6 mm at visit 7). CONCLUSIONS: Drospirenone 4 mg film-coated tablet in a dosage regime of 24/4 days is, regarding endometrial histology, a safe drug. Trial registration: EudraCT Register number: 2013-002300-13.

Prolonged use of finasteride-induced gonadal sex steroids alterations, DNA damage and menstrual bleeding in women.

The aim of the present study was to examine the effect of prolonged use of finasteride on serum levels of dihydrotestosterone (DHT), estradiol (E2), progesterone, testosterone and androstenedione in women during the menstrual period. Further, to screen and compare the 5α-reductase activities through the expression of SRD5A1, SRD5A2 and AR gene and to determine the level of VEGF, VKOR and SAA gene expression and DNA damage. A total of 30 Saudi women aged between 25 and 35 years were enrolled in the study. The selected women were divided into two groups. The first group (n = 15) received 5 mg finasteride/day for prolonged period of one year and second group (n = 15) was taken as a healthy control. ELISA technique was used for measuring the serum levels of the targeted hormones, and Comet assay was used for checking the DNA integrity. Our findings revealed significant decrement of DHT, E2, progesterone and androstenedione levels and elevated levels of testosterone in group treated with daily oral doses of 5 mg finasteride/day compared with the control subjects. mRNA expression suggested that finasteride has concrete effects on the gene expression of the selected genes from the treated group in comparison with the control group. In addition, finasteride induced DNA damage, and heavy menstrual bleeding was noted in women treated with finasteride. In conclusion, the present findings revealed that finasteride has adverse health effects in women associated with gonadal sex steroids alterations, DNA damage and heavy menstrual bleeding with no consensus in the treatment of androgenetic alopecia in women.

Experiences with Menses and Menstrual Suppression of Young Women with a History of Cancer.

Background: Adolescent and young adult (AYA) women undergoing multiagent chemotherapy are at risk for heavy menstrual bleeding (HMB). There is a paucity of data on the experiences with menses of AYA women with cancer, their risk for HMB, and how they perceive menstrual suppression. Objective: This study aimed to (1) describe the attitudes and experiences of AYA women with a history of cancer regarding their menses and menstrual suppression and to (2) investigate facilitators and barriers to improve this aspect of oncologic care. Design/Methods: AYA women with a history of cancer completed individual semistructured interviews regarding their experiences, attitudes, and preferences around menstrual health. Two independent reviewers conducted a thematic analysis of transcribed interviews to elicit major themes. Results: We interviewed 20 young women with a history of cancer (mean age 19.9 years) who were treated with chemotherapy within the past 5 years. Themes included the following: (1) negative feelings and worry about menstrual bleeding; (2) positive attitudes toward menstrual suppression; (3) misconceptions about menstrual health; and (4) desire for tailored discussions about menstrual suppression. Conclusions: AYA women with a cancer history elucidate clear opinions regarding menstruation during chemotherapy, and many hold misconceptions regarding menses and menstrual suppression. Enhanced patient-provider communication and patient educational resources around menstrual health and menstrual suppression are needed to improve comprehensive oncologic care during chemotherapy.

Case-based discussion on the implications of exogenous estrogens in hemostasis and thrombosis: the hematologist's view.

In the childbearing years, hormonal therapy or hormonal changes in the menstrual cycle or the puerperium may be complicated by bleeding or thrombosis; however, among women with congenital disorders of hemostasis and thrombosis, the risk of bleeding or thrombosis may be increased. In women with congenital bleeding disorders, heavy menstrual bleeding is the most common bleeding symptom, and postpartum hemorrhage occurs despite treatment. Given the limitations of current therapy and the associated medical and psychological burden in women with bleeding disorders, better treatment approaches are needed to improve health outcomes and quality of life. In women with congenital thrombotic disorders, thromboembolism may complicate exogenous hormonal therapy and endogenous hormonal change during pregnancy and procedures, but risk differs by type of thrombophilia, procedure, time at risk, and thrombosis risk factors, all of which affect management. In this article, I shall consider a case-based discussion of current issues in women with congenital bleeding and clotting disorders, including heavy menstrual bleeding in a woman with VWD, postpartum hemorrhage risk in VWD, and thrombosis risk with oocyte retrieval in a woman with factor V Leiden and past thromboembolism. The goals are to review bleeding or thrombosis risk in these cases, current data, limitations of current treatment guidelines, and areas for future study.

Intrauterine Devices: Effective Contraception with Noncontraceptive Benefits for Adolescents.

Although adolescent pregnancy and birth rates have been declining since the early 1990s, the rate of intrauterine device (IUD) use in adolescents remain low. IUDs are a highly effective contraceptive method with a failure rate of less than 1%. There are currently 5 IUDs available and marketed in the United States: the nonhormonal copper-containing IUD (Paragard Copper T380A; Ortho-McNeil) and 4 hormonal levonorgestrel-releasing intrauterine systems (LNG-IUDs). IUDs can be used in adolescents, and the LNG-IUD has many noncontraceptive benefits including the treatment of heavy menstrual bleeding, dysmenorrhea, pelvic pain/endometriosis, and endometrial hyperplasia/endometrial cancer. In addition, the LNG-IUD is an effective tool for suppression of menses.