Amenorrhea Rates Research Articles

Ulipristal acetate for Japanese women with symptomatic uterine fibroids: A double-blind, randomized, phase II dose-finding study.

PurposeA multicenter, randomized, double‐blind, placebo‐controlled trial was conducted to evaluate the efficacy, safety, and appropriate dose of ulipristal acetate (UPA) in Japanese women with symptomatic uterine fibroids (UFs).MethodsA total of 121 premenopausal women with UFs were enrolled to receive either placebo, UPA‐2.5 mg, UPA‐5 mg, UPA‐10 mg, or leuprorelin acetate (LEU), a reference drug, for 12 weeks. The primary end point was the rate of patients having achieved amenorrhea for 35 days at Week 12.ResultsThe rates for amenorrhea were 4.5%, 60.0%, 72.7%, 88.0%, and 76.2% in the placebo, UPA‐2.5 mg, UPA‐5 mg, UPA‐10 mg, and LEU groups, respectively. The median times to amenorrhea were 20.0, 5.0, 5.0, and 23.0 days for treatment with UPA‐2.5 mg, UPA‐5 mg, UPA‐10 mg, and LEU, respectively. A significant dose‐response of UPA for the rate of amenorrhea was observed. The overall incidence rates of adverse events were 45.8% in the placebo group, 56.5%‐80.0% in the UPA groups, and 100.0% in the LEU group. There were no notable safety issues with UPA.ConclusionsUlipristal acetate was effective and well tolerated in Japanese women with UFs. The recommended dose of UPA is considered to be 10 mg.

322. Prolonged Amenorrhea Is Associated with Decreased Hip Bone Mineral Density in Women Living with HIV

BackgroundWomen living with HIV (WLWH) have higher rates of long-term amenorrhea (no flow for ≥12 months) than HIV-negative women. However, little is known about the consequences of amenorrhea for WLWH. Both amenorrhea and HIV are associated with lower areal bone mineral density (BMD); though the combined effect of both on BMD remains unclear. In this cross-sectional study we investigated whether prolonged amenorrhea adversely affects BMD among WLWH.MethodsWe investigated BMD (using a Hologic bone densitometer) and prolonged amenorrhea among WLWH and HIV-negative control women of similar socioeconomic backgrounds aged 19–68 in the CARMA cohort. Participants were stratified by HIV status and history of prolonged secondary amenorrhea defined as a self-reported absence of menses for at least one year in the past or present, occurring at age <45 years and not due to surgery, breastfeeding, pregnancy or hormonal contraception. Hip and spine Z-scores (age- and race- standardized BMD values) were compared between groups using linear models, followed by multivariable analysis of BMD-related factors.ResultsWLWH (N = 129) had significantly lower hip (mean±SD −0.4 ± 0.9 vs. 0.3 ± 1.1; P < 0.001) and spine (−0.5 ± 1.3 vs. 0.2 ± 1.3; P = 0.001) Z-scores vs. controls (N = 129). Multivariable linear regression found prolonged amenorrhea was independently related to lower hip (P = 0.01), but not spine (P = 0.94) BMD. Within WLWH, the effect of amenorrhea was also additive to that of HIV, with hip Z-scores of -0.8±0.9for those with amenorrhea vs. -0.3±0.8for those normally cycling (P = 0.01). Amongst WLWH, those with prolonged amenorrhea had higher rates of illicit substance use, smoking, chronic opioid therapy, hepatitis C viral infection, and poorer HIV viral control than those with normal menstruation.ConclusionThese data suggest that WLWH having prolonged amenorrhea of ≥1 year’s duration are at increased risk for hip bone loss, a finding influenced by comorbid, HIV-associated conditions. Screening WLWH for menstrual history will allow early discovery of osteoporosis risk, and stimulate preventative measures to mitigate bone loss.Disclosures All authors: No reported disclosures.

1322 Comparison of Two Endometrial Ablation Techniques

Study Objective To compare the effectiveness of two methods (Novasure and Minerva) of endometrial ablation in a single community private practice. Design Retrospective chart review of all practice patients undergoing Novasure or Minerva endometrial ablation between 2015 and 2018. Minimum follow-up after the procedure was six months. Setting Procedures were all performed at Saddleback Center for Surgery (ambulatory surgery center) under general anesthesia by the physicians of Orange Coast Women's Medical Group. Patients or Participants All ablations performed between 2015 and 2018 were reviewed. 208 total ablations were performed. There were 127 in the Minerva cohort and 81 in the Novasure cohort. Interventions Not Applicable Measurements and Main Results Charts were reviewed for patient age, amenorrhea rates, rate of subsequent hysterectomy, improvement in bleeding, number of procedures performed by each provider, and days of follow up. Key results revealed no significant difference in the rate of amenorrhea in patients undergoing ablation with Minerva 32.3% (41/127) and Novasure 40.7% (33/81), (p=0.21). There was no significant difference in the rate of subsequent hysterectomy, 5.5% in the Minerva group and 9.9% in the Novasure group (p=0.24). There was no significant difference in patients showing improvement in bleeding without amenorrhea, 48.8% in the Minerva group and 44.4% in the Novasure group (p=0.72). There was no significant difference in the total combined amenorrhea and bleeding improvement; 81.1% in the Minerva group and 85.1% in the Novasure group (p= 0.45). Conclusion In our series, there was no significant difference in the Minerva or Novasure endometrial ablation systems in the rate of amenorrhea, subsequent hysterectomy, and overall decrease in bleeding.

1953 Ulipristal Acetate for Adenomyosis: A Multicenter Randomized Trial

Study Objective To evaluate efficacy of a 3 months course of ulipristal acetate on abnormal uterine bleeding in adenomyosis Design A multicenter randomized trial with a 3:1 ratio. Setting In five different teaching hospitals Patients or Participants Women with adenomyosis confirmed on MRI or sonography and abnormal uterine bleeding with PBAC score more than 100 Interventions Women were randomly assigned for a 3 months course of either 10mg Ulipristal acetate or a placebo Measurements and Main Results Main objective was the rate of women with a PBAC score under 75 after 3 months of treatment. The secondary objectives included rate of PBAC score under 75 at 6 months, rate of amenorrhea at 3 and 6 months, evolution of the pain and of the quality of life at 3 and 6 months and finally, tolerance. Forty women were included, 30 in the UPA group and 10 in the placebo group. The two groups were comparable particularly for PBAC score and analgesic consumption before the treatment. At 3 months, a significant difference was observed between UPA group and placebo group for the rate of PBAC score under 75 (0 versus 95.2%), p Conclusion Ulipristal acetate seems to stop abnormal uterine bleeding due to adenomyosis but also pain during a three months course but both of these symptoms reappeared at the stop of the medication. Other studies are needed to conclude and to try different doses.

1569 The Efficacy and Safety of Long-Term Management of Uterine Fibroids with Ulipristal Acetate

Study Objective To investigate the efficacy and safety of four repeated 12-week courses of 5 mg daily ulipristal acetate for intermittent treatment of symptomatic uterine fibroids. Design A retrospective, single-center observational study. Setting A university tertiary referral center. Patients or Participants One hundred seventy-one premenopausal women with symptomatic uterine fibroids. Interventions Four repeated 12-week treatment courses of daily 5 mg ulipristal acetate. Measurements and Main Results After four repeated 12-week courses, uterine bleeding was controlled in 93% of the women receiving 5 mg of ulipristal acetate. The rates of amenorrhea were 83% occurring within 9 days in the majority of patients receiving ulipristal acetate. The median changes in total fibroid volume were –17%. Headache and breast tenderness were the most common adverse events associated with ulipristal acetate but did not occur significantly more frequently. Pain showed marked improvements from screening, even during the off-treatment intervals. The safety profile of ulipristal acetate was confirmed, and repeated treatment courses did not increase the occurrence of adverse reactions. There were no significant changes in laboratory parameters during the study. Conclusion The results of this study demonstrate the efficacy and further support the safety profile of four repeated 12-week courses of 5 mg daily ulipristal acetate for intermittent treatment of symptomatic uterine fibroids.

2892 Minitouch Outpatient Endometrial Ablation for Heavy Menstrual Bleeding - The Way Forward!

Study Objective We have been carrying out Minitouch Outpatient ablation at two hospitals since 2015. We share our experience of 179 cases carried out between 2015-2018. Design Patients with heavy menstrual bleeding are offered Minitouch ablation if they have completed family and if medical management options have failed. Setting One district general hospital, one community hospital. Patients or Participants 20% Patients had significant comorbidities, such as body mass index >50, severe pulmonary hypertension and cardiac disease. Interventions All selected patients are given information leaflets and analgesia, and nurse contact numbers to discuss any queries. We carry out Transvaginal Ultrasound scan on all patients and endometrial biopsy unless already done prior to the procedure. Hysteroscopy is performed on patients with structural abnormalities, such as polyps or fibroids, when detected on pelvic ultrasound scan. Patients are instructed to have pre-procedure analgesia at home (Diclofenac, Ibuprofen, Paracetamol) and Entonox (inhaled nitrous oxide) is offered during the procedure. Patients received standard Minitouch treatment. Energy customization features have been used for optimum patient comfort since 2017. Measurements and Main Results No complications were reported. Full energy dose was not delivered in three cases due to patient discomfort. Mean pain scores were 6/10 (intra-procedure) and 1/10 (post-procedure). Overall Success rate was 86% (154/179) with amenorrhea rate of 29%. 18 (10%) patients received further treatments – 2 Gonadotropin-releasing hormone analogue, 7 Repeat Minitouch ablation and 9 Hysterectomy. 31 patients treated using energy customization features had increased comfort and an overall success rate of 93.5% (29/31). Conclusion Minitouch Outpatient ablation without anesthesia, sedation or paracervical block is a safe procedure with high success rates. Customization features enhanced patient comfort without affecting clinical outcomes.

Regimen-Specific Rates of Chemotherapy-Related Amenorrhea in Breast Cancer Survivors

Abstract Young women who have not begun or completed their desired childbearing at the time of diagnosis with breast cancer often wish to understand and minimize their risk of chemotherapy-related amenorrhea (CRA). However, the incidence of CRA after regimens that do not include either an anthracycline or a cyclophosphamide is poorly studied. For patients with human epidermal growth factor receptor 2–positive disease, anthracycline- and cyclophosphamide-sparing regimens (eg, carboplatin/taxane) are common (in combination with human epidermal growth factor receptor 2–directed therapy). In this study, accrued in collaboration with Army of Women, menstrual data were analyzed for 151 breast cancer survivors (median age = 41 years at diagnosis, and median time between last chemotherapy and survey = 62.5 months). Last menstrual period was before the last chemotherapy dose in 51% of the 86 participants who received anthracycline/cyclophosphamide/taxane, in 42% of the 43 who received only taxane/cyclophosphamide, and in 13% of the 15 who received carboplatin/taxane. This study suggests that carboplatin/taxane causes less CRA than cyclophosphamide-based regimens.

A combined, bioidentical, oral, 17β-estradiol and progesterone capsule for the treatment of moderate to severe vasomotor symptoms due to menopause

ABSTRACTIntroduction: Many women seek treatment to alleviate menopausal vasomotor symptoms (VMS). Numerous women use combination compounded hormone therapy (CHT) to achieve the benefits of estrogen/progesterone for endometrial protection. TX-001HR is a combination of bioidentical 17β-estradiol (E2) and progesterone (P4) in a single capsule designed for continuous daily use to treat moderate to severe VMS.Areas covered: This drug profile describes the efficacy and safety of 4 doses of this E2/P4 (mg/mg: 1/100, 0.5/100, 0.5/50, 0.25/50) for treating moderate to severe VMS in menopausal woman with a uterus.Expert opinion: In REPLENISH (NCT01942668), the two highest doses of TX-001HR significantly reduced VMS frequency and severity at 4 and 12 weeks versus placebo (co-primary endpoints); all doses met the primary endpoint of endometrial safety. Rates of amenorrhea were high and improved over time; the Menopause Quality of Life and Medical Outcomes Study-Sleep instruments improved with E2/P4. TX-001HR was well tolerated and had no clinically significant impact on vital signs, metabolic or coagulation parameters, or breast safety. The combination bioidentical E2/P4 capsule (1 mg/100 mg dose was FDA-approved as Bijuva in October 2018) may provide a safe, effective, rigorously studied alternative for women with a uterus who prefer CHT for relief of VMS.

Comparison of Combined Bipolar Radiofrequency Impedance-Controlled Endometrial Ablation with Levonorgestrel Intrauterine System versus Bipolar Radiofrequency Endometrial Ablation Alone in Women with Abnormal Uterine Bleeding

Study ObjectiveThis study aims to evaluate the efficacy of the combination of bipolar radiofrequency impedance-controlled endometrial ablation (NovaSure; Hologic Inc., Bedford, MA) and levonorgestrel intrauterine system (LNG-IUS; Mirena; Schering AG, Berlin, Germany) placement in comparison with NovaSure endometrial ablation alone in patients with abnormal uterine bleeding (AUB). DesignA propensity score matching study. SettingBeijing Tiantan Hospital, Capital Medical University, Beijing, China. PatientsA retrospective study was conducted on 246 patients with AUB who underwent NovaSure endometrial ablation with (NovaSure+LNG-IUS group) or without (NovaSure group) LNG-IUS between January 2013 and August 2016. To overcome selection bias, propensity score matching was used to establish a 1:1 match between these 2 groups. Accordingly, 41 patients were included in each group. InterventionNovaSure endometrial ablation, immediately followed by LNG-IUS insertion in the NovaSure+LNG-IUS group, and NovaSure endometrial ablation alone in the control group. Measurements and Main ResultsFollow-up assessments performed at postablation months 6, 12, and 24 revealed the following: The rate of amenorrhea (78.05% vs 46.34%, 85.37% vs 53.65%, and 87.80% vs 58.54%, respectively; p <.005) and the rate of dysmenorrhea remission (100% vs 70.59%, 100% vs 64.70%, and 100% vs 64.70% [p <.05, p <.01, and p <.01], respectively) were significantly higher in the NovaSure+LNG-IUS group than in the NovaSure group. The rate of reinterventions was similar for both groups at postablation month 6. However, at postablation months 12 and 24, these rates were significantly lower in the NovaSure+LNG-IUS group than in the NovaSure group (0 vs 14.63% and 2.44% vs 21.95% [p <.05 and p <.01], respectively). ConclusionFor women with AUB, the combination of NovaSure endometrial ablation and LNG-IUS is more effective than NovaSure alone in achieving amenorrhea, alleviating dysmenorrhea and reducing reinterventions.

Timing of postpartum etonogestrel-releasing implant insertion and bleeding patterns, weight change, 12-month continuation and satisfaction rates: a randomized controlled trial

ObjectivesTo evaluate whether timing of etonogestrel (ENG) implant insertion during the postpartum period affects maternal bleeding patterns, body mass index (BMI) and 12-month satisfaction and continuation rates. Study designThis is a secondary analysis of an open, randomized, controlled trial. Postpartum women were block-randomized to early (up to 48 h postpartum) or delayed (6 weeks postpartum) insertion of an ENG implant. Bleeding patterns and BMI were evaluated every 90 days for 12 months. At 12 months, we measured implant continuation rates and used Likert and face scales to measure users' satisfaction. The level of significance was 0.4% (adjusted by Bonferroni test for multiplicity). ResultsWe enrolled 100 postpartum women; we randomized 50 to early and 50 to delayed postpartum ENG implant insertion. Bleeding patterns were similar between groups. Amenorrhea rates were high in both groups during the follow-up (52%–56% and 46%–62% in the early and delayed insertion group, respectively). Prolonged bleeding episodes were unusual in both groups during the follow-up (0–2%). Maternal BMI was similar between groups and decreased over time. Twelve-month continuation rates were similar between groups (early insertion: 98% vs. delayed insertion: 100%, p=.99). Most participants were either very satisfied or satisfied with the ENG implant in both groups (p=.9). ConclusionWomen who underwent immediate postpartum insertion of the ENG implant have similar bleeding patterns, BMI changes, and 12-month satisfaction and continuation rates compared to those who underwent delayed insertion. ImplicationsOur results from a secondary analysis of a clinical trial support that satisfaction, continuation and bleeding patterns do not differ when women received contraceptive implants immediately postpartum or at 6 weeks. However, the emphasis on infant growth in the trial and easy access to delayed placement may have influenced results.

A cohort study comparing the severity and outcome of intrauterine adhesiolysis for Asherman syndrome after first- or second-trimester termination of pregnancy

ObjectiveTo compare the clinical characteristics of Asherman syndrome and the outcomes of hysteroscopic adhesiolysis in women after first or second-trimester termination of pregnancy (TOP). MethodsThis was a retrospective descriptive analysis of patients with moderate-to-severe intrauterine adhesiolysis (IUAs) after TOP and treated by hysteroscopic adhesiolysis and followed by “second-look” hysteroscopy 3 months later at The Beijing Obstetrics and Gynecology Hospital (China) between January 2013 and March 2016. The American Fertility Society (AFS) scoring system was used to evaluate the intrauterine adhesions. ResultsA total of 236 patients with 180 first-trimester TOP and 56 s-trimester TOP patients were included. The severe adhesion and amenorrhea rates during the second-trimester group (69.6% and 39.3%, respectively) were significantly higher than those in the first-trimester group (36.7% and 7.2%, respectively). AFS score reduction in the second-trimester group (6.2 ± 2.8) was significantly lower than in the first-trimester group (6.5 ± 2.5). The pregnancy rates in the second-trimester group (21.4%) were significantly lower than that in the first-trimester group (43.3%). The pregnancy rate of severe intrauterine adhesions in second-trimester TOP (10.3%) was significantly lower than in first-trimester TOP (40.9%). ConclusionThese findings suggested that second trimester TOP was associated with more severe intrauterine adhesion and a worse prognosis after hysteroscopic adhesiolysis in women with Asherman syndrome when compared to first-trimester TOP.

Comparing bleeding patterns for the levonorgestrel 52 mg, 19.5 mg, and 13.5 mg intrauterine systems

ObjectiveCompare bleeding patterns for levonorgestrel 52 mg, 19.5 mg, and 13.5 mg intrauterine system (IUS) products using the World Health Organization Belsey definitions. Study designWe extracted available data on bleeding patterns from published sources. Lower dose products had published data at 1 and 3 years; the 52 mg IUS had available data for 1, 2 and 3 years for amenorrhea and 1 and 2 years for other bleeding patterns. We interpolated 2-year data for the lower dose products based on 1- and 3-year data and compared bleeding pattern rates using Fisher exact testing. ResultsThe studies evaluated bleeding patterns in 1700, 1566 and 1531 women using levonorgestrel 52 mg, 19.5 mg and 13.5 mg products, respectively. Amenorrhea rates were greater by 180 days after insertion for 52 mg IUS users (11%) as compared to 19.5 mg (5%, p<.0001) and 13.5 mg (3%, p<.0001). Infrequent bleeding rates were higher for 52 mg users by the end of year 1 (31%) compared to 19.5 mg (26%, p=.01) and 13.5 mg (20%, p<.0001). Irregular bleeding rates were higher with the lower dose products by 90 days after insertion with continued lower rates at the end of year 1 for 52 mg users (6%) compared 19.5 mg (17%, p<.0001) and 13.5 mg (23%, p<.0001). Frequent and prolonged bleeding patterns were similar over the first 2 years for all products, although the rates were statistically higher for levonorgestrel 13.5 mg IUS users compared to 19.5 mg and 52 mg IUS users (p≤.03 for all time points after 90-days post-insertion). ConclusionsLevonorgestrel 52 mg IUS users have more amenorrhea and infrequent bleeding and less irregular bleeding compared to women using lower dose levonorgestrel IUS products. Implications StatementAll women considering levonorgestrel IUS placement should receive counseling on the differences in bleeding patterns related to the various available doses. Women who are interested in maximizing the likelihood of favorable bleeding should consider a levonorgestrel 52 mg IUS over the lower dose alternatives.

SAT-238 Predictors Of Vaginal/Uterine Bleeding With Oral TX-001HR (Estradiol and Progesterone) Capsules Taken For Menopausal Vasomotor Symptoms

Vaginal bleeding associated with hormone therapy (HT) is the most common reason for treatment discontinuation. Cumulative amenorrhea rates (no bleeding or spotting for 13 cycles) ranging from 23% to 49% with current HT options1-3 are relatively lower than the 56% to 73% observed in the REPLENISH trial.4 The REPLENISH trial (NCT01942668) was a 12-month, phase 3, randomized, double-blind, placebo-controlled, multicenter trial that evaluated TX-001HR (bioidentical 17β-estradiol and progesterone [E2/P4] combined in a single, oral softgel capsule; 1 mg E2/100 mg P4 FDA approved as BIJUVATM; TherapeuticsMD, Boca Raton, FL) vs placebo in 1835 menopausal women (40−65 y; intact uterus) for the treatment of menopausal, moderate to severe vasomotor symptoms (VMS). Overall, the proportion of women with no bleeding was high (74%-90%) with up to 1 year of TX-001HR. The objective of this analysis was to determine predictors of vaginal bleeding. Univariate analyses were used to assess the impact of age, race, BMI, smoking, time since last menstrual period (LMP), age at LMP, tubal ligation, parity, baseline E2 concentration, and baseline frequency and severity of VMS (mild=1 to severe=3) on the incidence of vaginal bleeding at any time during the study (cumulative incidence at cycle 13) and for bleeding that occurred in the first 3 months of the study (cumulative incidence at cycle 3). Predictors of vaginal bleeding with HT (at cycle 13) were age, time since LMP, E2 concentration, and severity of VMS. The likelihood of bleeding was reduced by 42% for every 5-year increase in age (P<0.0001) and by 39% for every 5-year increase in the time since LMP (P<0.0001). Incidence of bleeding significantly decreased by 54% with baseline E2 levels <10 pg/mL (P=0.0001), 59% with E2 levels <5 pg/mL (P<0.0001), and 47% for E2 levels 5 to <10 pg/mL (P=0.0040), when compared with E2 levels ≥10 pg/mL. There was 33% less bleeding reported for women with less severe VMS (<2.5 points). No statistically significant differences in reports of bleeding were noted for race, BMI, smoking, age at LMP, tubal ligation, parity, or baseline frequency of moderate to severe VMS. Similar predictors were noted for bleeding at cycle 3, except for baseline VMS severity, which was no longer a significant predictor. Cumulative amenorrhea was relatively high in TX-001HR users. Vaginal bleeding in women treated with TX-001HR increased in women who were younger, experienced their LMP more recently, and had higher baseline E2 concentrations. Even though the rate/amount of bleeding was relatively low overall,4 these data may help clinicians inform women who may be more likely to experience vaginal bleeding while taking combined E2/P4 for menopausal symptoms. 1. Prempro tablets PI. Wyeth Pharmaceuticals. 2. Activella tablets PI. Novo Nordisk FemCare AG. 3. Angeliq Tablets PI. Berlex. 4. Lobo RA, et al. Obstet Gynecol. 2018;132:161-170.

Abstract P1-12-10: Regimen-specific rates of chemotherapy-related amenorrhea in breast cancer survivors

Abstract Background: Chemotherapy can damage the ovaries and cause amenorrhea, a surrogate for infertility. Young women often wish to understand and minimize their risk of chemotherapy-related amenorrhea (CRA). However, the incidence of CRA with regimens that do not include either an anthracycline or cyclophosphamide is poorly studied. For patients with HER-2 positive disease, these anthracycline and cyclophosphamide-sparing regimens (e.g., docetaxel-carboplatin) are common (in combination with Her-2 directed therapy) in both the neoadjuvant and adjuvant settings. Methods: Women diagnosed with breast cancer under age 50 and within the past 10 years were recruited through a Dr. Susan Love Research Foundation Army of Women e-mail blast. Those who provided their contact information were mailed a consent form and medical record authorization form. Participants then received a web-based survey that inquired about receipt of and type of chemotherapy (including date of last dose) and date of last menstrual period (LMP). Patient-reported LMP was compared to date of final chemotherapy dose to determine if the LMP occurred before (defined as “CRA”) or after the last chemotherapy dose. When available, medical record data was used in place of survey data regarding type of chemotherapy used. Exclusion criteria included: LMP prior to diagnosis date, receipt of multiple chemotherapy regimens or no chemotherapy regimens, receipt of ovarian suppression medications (which interfere with interpretation of menstrual data), surgical menopause prior to or at the same time as diagnosis, a cancer diagnosis more than 10 years prior, incomplete menstrual data on the survey, report of an unknown chemotherapy regimen, and no date available for the last chemotherapy dose without an LMP within a month prior to survey completion. Fisher Exact test was used to compare CRA rates between regimens. Rates after two anthracycline-sparing regimens (taxane/cyclophosphamide; taxane/carboplatin) were compared to rates after anthracycline/cyclophosphamide/taxane. Results: 273 women consented to participate in this study, 258 of whom filled out the web survey. 151 of them were eligible for this analysis with a median age at diagnosis of 41 (range 24-49) and a median time from last chemotherapy dose to survey of 62.5 months (range 2-138). CRA occurred in 51.2% of the 86 participants who received an anthracycline, cyclophosphamide, and a taxane, in 41.9% of the 43 participants who received only a taxane and cyclophosphamide (p=0.35), and in 13.3% of the 15 participants who received carboplatin with a taxane (p=0.01). When the 11 patients who were &amp;lt;12 months since last chemotherapy were excluded, CRA rates changed minimally. Age did not differ by regimen, but median time since chemotherapy was shorter in the taxane/carboplatin group (35 months vs. 68 months). Trastuzumab with or without pertuzumab was administered in 100% of patients who received carboplatin/taxane, in 23.3% of patients who received taxane and cyclophosphamide, and in 22.1% of patients who received anthracycline/cyclophosphamide/taxane. Conclusions: This study suggests that carboplatin/taxane may be substantially less gonadotoxic than cyclophosphamide-based (neo)adjuvant regimens. Further research is necessary to confirm these findings. Citation Format: Gast KC, Cathcart-Rake EJ, Norman A, Eshragi L, Obidegwu N, Yost K, Nichols HB, Rosenberg S, Su HI, Stewart E, Couch F, Vachon C, Ruddy KJ. Regimen-specific rates of chemotherapy-related amenorrhea in breast cancer survivors [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-12-10.

Oncofertility counselling in premenopausal women with HER2-positive breast cancer.

A complete oncofertility counselling should be offered to all premenopausal patients before the administration of anticancer treatments. This important discussion is a crucial step for allowing them to take fully informed decisions about the proposed therapy and its potential long-term consequences as well as on their need and interest of accessing the available strategies for ovarian function and/or fertility preservation. In premenopausal women with HER2-positive early breast cancer, limited evidence exists to counsel them about the potential added gonadotoxicity of targeted agents beyond the damage already caused by chemotherapy. In addition, the prognostic role of treatment-induced amenorrhea in this setting was unknown. In our exploratory analysis within the ALTTO (BIG 2-06) trial, we have recently described the rates of treatment-induced amenorrhea after chemotherapy plus trastuzumab and/or lapatinib and the prognostic value of developing this side effect according to the hormone receptor status of their tumours. We observed similar rates of treatment-induced amenorrhea in the four anti-HER2 treatment arms. The lack of an increased rate of treatment-induced amenorrhea in the dual anti-HER2 blockade arm suggests the possible gonadal safety of these agents. In addition, women with HER2-positive/hormone receptor-positive tumours showed significantly better survival outcomes if they developed treatment-induced amenorrhea, while no difference was observed for those with HER2-positive/hormone receptor-negative disease. Future research efforts are needed to address the gonadotoxicity of the new available targeted agents as well as to elucidate which is the best adjuvant endocrine therapy in premenopausal women with HER2-positive/hormone receptor-positive disease.

Amenorrhea and Menopause in Patients with Breast Cancer after Chemotherapy.

PurposeThe probability of ovarian failure after cytotoxic chemotherapy in patients with breast cancer has not been well established in Korea. This study aimed to assess the rate of ovarian failure in a large cohort of Korean premenopausal patients with breast cancer 12 months after chemotherapy.MethodsThis retrospective cohort study included premenopausal women (aged 20−44 years) with breast cancer who underwent chemotherapy after surgery. The rates of treatment-related amenorrhea (TRA) and chemotherapy-induced menopause (CIM) at 12 months after chemotherapy were analyzed.ResultsA total of 237 patients met the inclusion criteria. The rate of TRA was 61.6% and that of CIM was 13.1% at 12 months after chemotherapy. The rates of TRA and CIM were 28.0% and 4.0%, respectively, in women aged 25−34 years, and they gradually increased up to 75.9% (TRA) and 15.8% (CIM), respectively, in women aged 40−44 years. The frequency of CIM was significantly lower than that of TRA in both age groups. In multivariate analyses, only tamoxifen use was significantly associated with a decreased risk of CIM (p < 0.001). Age of 40 years or higher and the regimens of doxorubicin plus cyclophosphamide followed by docetaxel or paclitaxel were associated with increased risk of TRA (p = 0.001 and p = 0.002, respectively).ConclusionMarked discrepancy in the rates of CIM and TRA was observed in this study. Further, the age-specific frequency of CIM and TRA observed in this study is a reliable and practical estimate of the risks of CIM and TRA in the absence of gonadal protection.

Radiofrequency endometrial ablation for treating heavy menstrual bleeding in women with chronic renal failure

Objective: The study objective was to retrospectively evaluate the efficacy and safety of radiofrequency endometrial ablation in treating heavy menstrual bleeding (HMB) in women with chronic renal failure (CRF).Method: Fifty-eight patients with CRF undergoing radiofrequency endometrial ablation in our hospital between January 2013 and July 2017 and for whom complete follow-up data were available were included. Outcome measures included amenorrhea, treatment failure and operative complications.Results: The mean patient age was 41.4 ± 7.7 years, the mean preoperative hemoglobin level was 69.6 ± 19.3 g/dL, the mean preoperative serum creatinine level was 879.1 ± 415.4 µmol/L, and the mean urea level was 18.2 ± 7.1 mmol/L. The mean treatment time for radiofrequency endometrial ablation was 61.7 ± 18.8 s. The median volume of estimated blood loss during the procedure was 10 mL (a range of 2–50 mL). On average, the study subjects were monitored for 24.4 months (a range of 6–60 months). The average amenorrhea rate was 89.7%. Only 2 (3.4%) patients required additional gynecologic surgery after endometrial ablation. Intra- and postoperative complications were not observed.Conclusion: Radiofrequency endometrial ablation was demonstrated to be safe and effective for the treatment of HMB in women with CRF.

Vaginal bleeding/spotting with conjugated estrogens/bazedoxifene, conjugated estrogens/medroxyprogesterone acetate, and placebo

ABSTRACTObjective: In the 1-year phase 3 Selective estrogens, Menopause, And Response to Therapy-5 trial, cumulative amenorrhea rates with conjugated estrogens/bazedoxifene (CE/BZA) were similar to placebo and higher than with conjugated estrogens/medroxyprogesterone acetate (CE/MPA). This post hoc analysis reports bleeding/spotting rates in 4-week intervals (cycles) and 3-month intervals (quarters) with these therapies and the percentage of cases attributable to spotting only.Methods: Generally healthy postmenopausal women with menopausal symptoms recorded vaginal bleeding/spotting in daily diaries while receiving CE 0.45 mg/BZA 20 mg, CE 0.625 mg/BZA 20 mg, CE 0.45 mg/MPA 1.5 mg, or placebo.Results: A total of 1596 women in the modified intent-to-treat population contributed data. Incidence of bleeding/spotting was significantly (p < 0.001) lower with CE 0.45 mg/BZA 20 mg (0.54‒4.44%), CE 0.625 mg/BZA 20 mg (1.26‒5.02%), and placebo (1.55‒4.82%) compared with CE 0.45 mg/MPA 1.5 mg (8.81‒25.63%) in all 4-week cycles. Each quarter, <10% of women taking CE/BZA doses or placebo had bleeding/spotting, significantly (p < 0.001) less than the 21–36% with CE 0.45 mg/MPA 1.5 mg. Odds ratio for bleeding/spotting with CE 0.45 mg/BZA 20 mg vs CE 0.45 mg/MPA 1.5 mg was 0.1 in each quarter (95% CI, Q1–Q3: 0.1–0.2; Q4: 0.1–0.3). Across all treatments, most (88–100%) bleeding/spotting cases were spotting only. Mean days of bleeding/spotting were <1 per quarter with CE/BZA doses and placebo, which was significantly (p < 0.01) less than the 3–5 days per quarter with CE/MPA.Conclusions: Bleeding/spotting with CE/BZA treatment was similar to placebo and significantly less frequent than with CE/MPA treatment. Most cases were spotting only across all treatments.

Prevalence and predictors of oligomenorrhea and amenorrhea in division 1 female athletes

Long-term health is impacted by disorders of hypothalamic-pituitary-ovarian (HPO) axis that frequently manifest as oligomenorrhea and amenorrhea. Elite female athletes represent a group who may be at higher risk of HPO disorders. Despite long-standing observations that strenuous exercise, stress and weight impact the HPO axis, little is known the prevalence and predictors of oligo/amenorrhea in this population.Consequently, there exists a need for a comprehensive dataset to explore menstrual patterns and systemic hormone use in elite athletes. We conducted a cross sectional survey study in order to answer these questions. This is a descriptive online cross-sectional survey study. This is a subset analysis of a larger study by the same group of investigators. This survey was distributed to 455 Division 1 Female athletes at the University of Wisconsin via an online platform. Statistical analysis was performed in STATA and JMP by the Obstetrics and Gynecology statistics team. Bivariate chi square and descriptive statistical analysis was performed. Response rate was 49% with a total of 224 respondents. Average self-reported age was 20 and BMI (based on height/weight) was 22. The athletes reported 11 different sports with endurance athletes representing 57% of all respondents. Eumenorrhea (reported menstrual cycles every 4 weeks) was reported by 67%. Rate of amenorrhea was 5% and rate of oligomenorrhea was 24%. 5% of women reported bleeding more than every two weeks. Underweight athletes (BMI<20) were not more likely to be oligomenorrheic or amenorrheic when compared with athletes of normal BMI or overweight athletes, however, all amenorrheic athletes had BMI of less than 25. Cross country and track athletes were more likely to be underweight when compared with the eleven other sports (22%, p< 0.02). Underweight athletes were less likely to use a systemic hormonal contraceptive method when compared with normal and overweight athletes (29%, p< 0.03). Our study design does not distinguish between WHO type I and II amenorrhea, so some athletes studied may have PCOS instead of more typical hypothalamic anovulation, a question we will explore in the future. This study provides further evidence of menstrual dysfunction in elite female athletes. Overall prevalence of menstrual dysfunction in our cohort was 33%, which is higher than prior studies quoted in the literature. Menstrual dysfunction occurs regardless of BMI, although it is important to note that all amenorrheic athletes had BMI <25, suggesting that disruption in the HPO axis can occur without decreased energy availability. Consequently, screening for female athlete triad should be broad and include athletes of normal BMI, as BMI alone may not be fully predictive of menstrual dysfunction. Finally, low uptake of systemic hormonal contraception by the underweight cohort is potentially troubling, due to long-term consequences of hypoestrogenemia, and suggests a target intervention group.

Impact of chemotherapy on ovarian function and quality of life of patients with gestational trophoblastic neoplasia

Objective: Using a questionnaire to evaluate different regimens of chemotherapy on ovarian function and quality of life of patients with gestational trophoblastic neoplasia (GTN) . Methods: At least 6 months after completion of chemotherapy, 200 patients with GTN treated in Peking Union Medical College Hospital from January 2010 to June 2017 were randomly selected to fill up the questionnaire. The questionnaire items were included the patient's menstrual cycles, sexual life, gestational issues and common health. The patients were divided into 3 groups by chemotherapy regimens: actinomycin D (Act-D) group, floxuridine+Act-D+vincristine (FAV) or floxuridine+Act-D+etoposide+vincristine (FAEV) group (FAV-FAEV group) , and etoposide+methotrexate+Act-D (EMA) /vincristine+cyclophosphamide (CO) or EMA/ etoposide+cisplatin (EP) group (EMA/CO-EMA/EP group) . Chi-square test was used with a significance level of P-value less than 0.05. Results: One hundred and seventy-three (86.5%,173/200) of the patients completed the questionnaire. Forty three point two percent (43.2%, 19/44) in the EMA/CO-EMA/EP group had a normal menstrual cycle, which were significantly lower than those of Act-D group (84.6%,22/26) and FAV-FAEV group (71.2%, 37/52; all P<0.05) . Amenorrhea rate was also significantly higher in EMA/CO-EMA/EP group (25.0%, 11/44) than in Act-D group (0) and FAV-FAEV group (17.3%, 9/52; all P<0.05) . The sexual life parameters were comparable among 3 groups. Ten out of thirty-two patients conceived after chemotherapy, 2 had miscarriages and 8 had full-term delivery of healthy babies. The common health and labor capacity were significantly decreased after chemotherapy (all P<0.05) . Conclusions: EMA/CO or EMA/EP regimen have a worse impact on ovarian function than Act-D and FAV or FAEV regimen. Gynecologic oncologist should be concerned about the ovarian function and quality of life of GTN patients.