Real-world anticancer medications for reproductive-age women with breast cancer by using a claims database in Japan.

Aim: To describe real-world breast cancer medications among reproductive-age women. Patients & methods: Using data from a Japanese claims database, anticancer prescriptions were classified into seven categories of amenorrhea risk based on fertility preservation guidelines. Results: We identified 2999 women with records of breast cancer and anticancer prescription from 2005 to 2018. The proportions of prescriptions were as follows: high, 4.1-12.9%; intermediate: 6.0-16.3%; low: 0.4-2.3%; very low/no: 0.3-12.2%; unknown: 33.9-45.5%; unlisted combination: 12.2-23.4%; and unlisted drug: 12.5-26.7%. The common drugs in the unknown category were trastuzumab (n = 1527), docetaxel (n = 1014), and paclitaxel (n = 995). For medications unlisted in the guidelines, various drugs and drug combinations were observed. Conclusion: Numerous anticancer drugs are currently being prescribed with insufficient evidence regarding amenorrhea risk.

Lay abstract The ability to have children for breast cancer patients is one of the key issues of cancer survivorship, especially because recent progress in anticancer treatments has enabled patients to achieve longer survival. The fertility preservation guidelines of the American Society of Clinical Oncology (2006) introduce some anticancer treatments that carry potential risks to future fertility. In this study, the anticancer prescriptions of 2999 patients with breast cancer aged between 15 and 49 years were examined. Results showed that several medications are prescribed despite the lack of information on the risk of infertility. This suggests that further research is required to fill the evidence gap, and that decision aid through adequate counseling should be undertaken.

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.

Low Bone Mineral Density in Elite Female Athletes With a History of Secondary Amenorrhea in Their Teens.

OBJECTIVE: To determine whether secondary amenorrhea during teenage years influences bone mineral density (BMD) in female athletes in their 20s. DESIGN: Original research. SETTING: Japan Institute of Sports Sciences. PARTICIPANTS: Two hundred ten elite female athletes older than 20 years were included in the study. MAIN OUTCOME MEASURES: Information on the participants' past (ie, during their teenage years) and current menstrual cycle, training time, history of stress fractures, and blood tests for hormones received was obtained. Bone mineral density of the lumbar spine was evaluated by dual-energy x-ray absorptiometry; low BMD was defined as a Z-score ≤-1. We investigated the correlation factors for low BMD in athletes in their 20s by univariable and multivariable logistic regression analysis. RESULTS: A total of 39 (18.6%) female athletes had low BMD. Secondary amenorrhea in their teens [odds ratio (OR), 7.11, 95% confidence interval (CI), 2.38-21.24; P < 0.001] and present body mass index (BMI) (OR, 0.56, 95% CI, 0.42-0.73; P < 0.001) were independent correlation factors for low BMD in the multivariable logistic regression analysis. The average Z-score for those with secondary amenorrhea in their teens and 20s, secondary amenorrhea in their 20s only, and regular menstruation was -1.56 ± 1.00, -0.45 ± 1.21, and 0.82 ± 1.11 g/cm, respectively. CONCLUSIONS: Secondary amenorrhea for at least 1 year during teenage years in female athletes and BMI at present was strongly associated with low BMD in their 20s.

Individualized Prediction of Menses Recovery After Chemotherapy for Early-stage Breast Cancer: A Nomogram Developed From UNICANCER PACS04 and PACS05 Trials.

BACKGROUND: The likelihood of menses recovery varies greatly in premenopausal patients receiving adjuvant chemotherapy for breast cancer. Quantifying this probability for each patient could better inform the chemotherapy discussion and individualize fertility counseling. We performed a pooled analysis of the PACS04 and PACS05 adjuvant randomized trials to develop a nomogram to estimate the probability of menses recovery at 3, 6, and 18 months after the end of adjuvant chemotherapy. PATIENTS AND METHODS: Women who were premenopausal and aged ≤ 50 years at randomization in the PACS04 and PACS05 trials were included in the present analysis. The primary endpoint was the probability of menses recovery within 18 months of chemotherapy completion. Multivariable Cox proportional hazards regression was used to estimate the association of each variable with the likelihood of menses resumption. A nomogram was developed to predict menses recovery at different intervals. RESULTS: The factors associated with menses recovery were assessed for 1210 patients. At a median follow-up of 90 months (range, 3-189 months), 342 of 1210 patients (28.2%) had recovered menses. The probability of menses recovery at 18 months was 25.5% (range, 23.0%-27.9%). After backward elimination, age, final body mass index, type of chemotherapy, and hormone therapy were selected to build the nomogram to predict the probability of menstrual resumption at 3, 6, and 18 months after chemotherapy. CONCLUSION: An accurate and individualized prediction of menses recovery is feasible for premenopausal patients eligible for adjuvant chemotherapy for early-stage breast cancer. Our nomogram will be externally validated in a large prospective cohort.

Adjunct Aripiprazole Reduces Prolactin and Prolactin-Related Adverse Effects in Premenopausal Women With Psychosis: Results From the DAAMSEL Clinical Trial.

PURPOSE/BACKGROUND: Prolactin-related adverse effects contribute to nonadherence and adverse health consequences, particularly in women with severe mental illness. Treating these adverse effects may improve treatment acceptability, adherence, and long-term outcomes. METHODS/PROCEDURES: Premenopausal women with a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision diagnosis of schizophrenia, schizoaffective disorder, or bipolar disorder were recruited for a randomized, double-blind, placebo-controlled 16-week trial of adjunct aripiprazole (5-15 mg/d). Participants had elevated prolactin (>24 ng/mL) and were experiencing galactorrhea, amenorrhea, oligomenorrhea, or sexual dysfunction on a prolactin-elevating antipsychotic. Participants were evaluated biweekly for prolactin elevation and galactorrhea and completed a menstrual diary review. Psychiatric symptoms and adverse effects were closely monitored. FINDINGS/RESULTS: Forty-six women were randomized (n = 25 aripiprazole, n = 21 placebo). Thirty-seven completed at least 8 weeks of the study (n = 20 [80%] aripiprazole and n = 17 [81%] placebo). Aripiprazole (mean dose, 11.7 ± 2.4 mg/d) was effective for lowering prolactin relative to placebo (P = 0.04). In addition, 45% (9/20) of the aripiprazole group had a normalized prolactin (<24 mg/mL) compared with 12% (2/17) of the placebo group (P = 0.028). Galactorrhea resolved in 77% (10/13) of the aripiprazole-treated participants compared with 33% (4/12) in the placebo group (P = 0.028). Normalization of sexual function (<16 on the Arizona Sexual Experience Scale) occurred in 50% on aripiprazole (7/14) versus 9% (1/11) on placebo (P = 0.030). No differences between groups in symptoms or adverse effects were noted. Overall, women rated a mean score of 4.6 ± 0.6 on a 5-point Likert scale for sexual function improvement, suggesting their particular satisfaction with improvement in this domain. IMPLICATIONS/CONCLUSIONS: Building upon prior studies, this rigorous evaluation confirms the utility of adjunctive aripiprazole as a strategy for improving prolactin and managing prolactin-related adverse effects in premenopausal women with psychosis.

GnRH agonist for protection against ovarian toxicity during chemotherapy for early breast cancer: the Anglo Celtic Group OPTION trial.

BACKGROUND: Chemotherapy-induced premature ovarian insufficiency (POI) impacts fertility and other aspects of women's health. The OPTION trial tested whether administration of a gonadotropin-releasing hormone agonist during chemotherapy for early breast cancer reduced the risk of POI. PATIENTS AND METHODS: This was a prospective, randomized, parallel group study of the gonadotropin-releasing hormone agonist goserelin administered before and during chemotherapy for breast cancer with stage I-IIIB disease. The primary outcome was amenorrhoea between 12 and 24 months after randomization, supported by elevated follicle stimulating hormone concentrations to give an additional analysis as rate of POI. RESULTS: A total of 227 patients were randomized and the primary analysis was conducted on 202 patients. Goserelin reduced the prevalence of amenorrhoea between 12 and 24 months to 22% versus 38% in the control group (P = 0.015) and the prevalence of POI to 18.5% versus 34.8% in the control group (P = 0.048). Follicle stimulating hormone concentrations were also lower in all women treated with goserelin at both 12 and 24 months (P = 0.027, P = 0.001, respectively). The effect of goserelin was not statistically significant in women >40 years. Assessment of the ovarian reserve using anti-Müllerian hormone showed a marked fall in both groups during treatment to median values of 5% of pretreatment levels in the control group and 7% in the goserelin group, which were not significantly different between groups. CONCLUSION: This study shows that goserelin reduced the risk of POI in women treated with chemotherapy for early breast cancer, with particular efficacy in women aged ≤40 years old. The degree of ovarian protection also seems limited and the clinical significance for fertility and longer term prevention of estrogen deficiency-related outcomes needs to be determined.

Body fat and menstrual resumption in adult females with anorexia nervosa: a 1-year longitudinal study.

BACKGROUND: The variables predicting the resumption of menses in anorexia nervosa (AN) after weight restoration have not yet been fully established. We therefore aimed to investigate the association between several clinical parameters at inpatient discharge and the resumption of menses at 1-year follow-up in weight-restored adults with AN. METHODS: Demographic, anthropometric, body composition and eating disorder features were assessed in 54 adult females with AN who had restored normal body weight [body mass index (BMI) ≥ 18.5 kg m(-) ²] at the end of specialist inpatient treatment. These variables were compared between participants who had resumed menses and those who were still amenorrheic 1 year after inpatient discharge. RESULTS: At 1-year follow-up, 35.2% of patients had resumed menstruation. No significant association was found between the resumption of menses and either age, duration of illness or BMI at inpatient admission, nor for BMI, global Eating Disorder Examination score or trunk fat percentage at inpatient discharge. Only total body fat percentage at inpatient discharge was significantly higher in patients who resumed menstruation, as confirmed by combined logistic regression analysis (odds ratio = 1.14, 95% confidence interval = 1.001-1.303, P = 0.049). CONCLUSIONS: A higher total body fat percentage at inpatient discharge is associated with the resumption of menses at 1-year follow-up in weight-restored adult females with AN.

Characterization of endocrine features and genotype-phenotypes correlations in blepharophimosis-ptosis-epicanthus inversus syndrome type 1.

OBJECTIVE: Blepharophimosis syndrome (BPES) is an autosomal dominant genetic condition resulting from heterozygous mutations in the FOXL2 gene and clinically characterized by an eyelid malformation associated (type I) or not (type II) with premature ovarian failure. The distinction between the two forms is critical for female patients, as it may allow to predict fertility and to plan an appropriate therapy. Identifying an underlying causative mutation is not always predictive of the clinical type of BPES since genotype-phenotype correlations are not yet fully delineated. Here, we describe the clinical and hormonal phenotypes of three female patients with BPES type 1 from two novel families, correlate their phenotypes with identified mutations, and investigate the effects of hormone replacement therapy (HRT). METHODS: Clinical, biochemical, and genetic evaluation were undertaken in all the patients and genotype-phenotype correlation was analyzed. The effects of substitutive hormonal therapy on secondary sexual characteristics development and induction of menarche were evaluated. RESULTS: All patients presented with primary amenorrhea or other signs of ovarian dysfunction. Two distinct mutations, a missense p.H104R change and an in-frame p.A222_A231dup10 duplication in the FOXL2 gene were identified. Observed phenotypes were not in accordance with the prediction based on the current genotype-phenotype correlations. HRT significantly improved secondary sexual characteristics development, as well as the induction of menarche. CONCLUSIONS: This study highlights the importance of early recognition of BPES and emphasizes the need of personalized therapy and follow-up in female patients carrying distinct FOXL2 mutations.

Case of early postoperative adhesion in a patient with molimina due to transverse vaginal septum concomitant with imperforate hymen.

Transverse vaginal septum is a residual vaginal plate composed of the Müllerian duct and urogenital sinus. Imperforate hymen results from failure of perforation of the membrane between the urogenital sinus and vaginal cavity. We report a rare case of concurrence of these two conditions. A 16-year-old girl had been treated with puncture several times for hematometra and hematocolpos from 13 years of age because of monthly occurrence of lower abdominal pain without menstrual bleeding and was referred to our hospital. Magnetic resonance imaging demonstrated hematometra, hematocolpos and expansion of the vaginal fornix. The imperforate hymen was incised and a slight adhesion at the lower vaginal cavity was detached. After that, a complete transverse vaginal septum, which was 5 mm thick, was identified. It was excised after ultrasonography-guided puncture. Although two cycles of menstrual bleeding took place, molimina recurred. Re-operation was performed 6 months after the first operation, and recurrence of adhesion in the lower vaginal cavity was identified. A silicon dilator was inserted, but she could not use it at home and instead used a tampon. Cyclic menstrual bleeding is observed 4 months after the second operation.

Post-traumatic amenorrhea: the role of diagnostic and operative hysteroscopy in the prevention, diagnosis, differential diagnosis and treatment.

AIM: The aim of the study was to evaluate the clinical usefulness of the selective removal of residual intrauterine trophoblastic tissue by using a hysteroscopic procedure, especially in the prevention of the Intra-Uterine Adhesion's Syndrome. METHODS: Seventy-six patients had an Asherman's Syndrome: 5 cases after laparotomic myomectomy, 1 after caesarean section, 2 after hysteroscopic myomectomy, 10 after VIP, 1 with a severe vaginal endometriosis, 1 after conisation, 4 after a post-partum hemorrhage due to coagulopathy or uterine atony, 20 cases after D&C because of PPH due to placental retention, 26 after repetitive D&Cs because of AUB due to post abortion chorial residues' retention, 6 cases after D&C for post menopausal AUB. Thirty-six patients presented AUB due to chorioplacental residues retention: 14 cases after a vaginal delivery or a caesarean section, 4 after VIP, 18 cases after repetitive D&Cs for incomplete or internal spontaneous abortion. Complete physical examination, transvaginal ultrasonography and operative hysteroscopy was offered as first treatment to all patients. Surgical treatment of IUA depends on the type (I-IV) and is based on the section of synechiae, liberation of the uterine cavity and tubal recesses, recovery of the residual endometrium to restore the physiology of the reproductive tract. Our technique to remove the chorioplacental residues is based on: correct use of loops and electric currents, enucleation by cold loops of the base of the placental implant, and to single out the level of miometrial infiltration. RESULTS: After treatment we have noticed: two hysterectomies (for persistent AUB after myomectomy and for severe bleeding after dehiscence of a C. section), restoration of regular menstruations in 94.6% of patients (6 women in menopause), disappearance of pelvic pain and dysmenorrhea in all cases (100%), 8 pregnancies of the 9 women who were wanting child after hysteroscopic synechiolysis (88.9%). CONCLUSION: According to the present study, the best way to prevent IUA is to make D&C for abortion, avoiding waiting longer than 24 hours, perform a D&C and then a diagnostic hysteroscopy after PPH in symptomatic women, reserve D&Cs only for a PPH, or an incomplete abortion, limit to only one D&C, always make a diagnostic hysteroscopy after D&C and uterine plugging for PPH.

Body composition, eating disorder psychopathology, and psychological distress in anorexia nervosa: a longitudinal study.

BACKGROUND: Although the effect of immediate weight restoration on body composition and body fat distribution has previously been studied in anorexia nervosa (AN), its influence in women with AN on eating disorder psychopathology and psychological distress has not previously been investigated to our knowledge. OBJECTIVES: We assessed body composition and fat mass distribution before and after body weight restoration and investigated any relation between changes in body fat patterns of patients with AN treated in a specialist inpatient unit and their eating disorder and psychological distress features. DESIGN: Body composition was measured by using dual-energy X-ray absorptiometry in 50 female, adult patients with AN before and after complete weight restoration [body mass index (BMI; in kg/m²) ≥18.5] and 100 healthy control subjects matched by age and posttreatment BMI of study group participants. Eating disorder psychopathology and psychological distress were assessed in the AN group before and after weight restoration by using the Eating Disorder Examination interview and the Global Severity Index of the Brief Symptom Inventory (BSI-GSI), respectively. RESULTS: After the achievement of complete weight restoration, patients with AN had higher trunk (P < 0.001), android (P < 0.001), and gynoid (P < 0.001) fat masses and lower arm (P < 0.001) and leg (P = 0.001) fat masses with respect to control subjects. No relation was shown between body-composition variables and eating disorder psychopathology in the AN group, and the only significant predictor of change in BSI-GSI was the baseline BSI-GSI score. CONCLUSION: The normalization of body weight in patients with AN is associated with a preferential distribution of body fat in central regions, which does not, however, seem to influence either eating disorder psychopathology or psychological distress scores.

Comparison between effects of myo-inositol and D-chiro-inositol on ovarian function and metabolic factors in women with PCOS.

Myo-inositol and D-chiro-inositol are capable of improving the ovarian function and metabolism of polycystic ovary syndrome (PCOS) patients. The aim of this work is to compare the effects of myo-inositol and D-chiro-inositol in PCOS. We enrolled 50 patients, with homogeneous bio-physical features, affected by PCOS and menstrual irregularities, and we randomly divided them into two groups: 25 were treated with 4 g of myo-inositol/die plus 400 mcg of folic acid/die orally for six months, 25 with 1 g of D-chiro-inositol/die plus 400 mcg of folic acid/die orally for six months. We analyzed in both groups pre-treatment and post-treatment BMI, systolic and diastolic blood pressure, Ferriman-Gallwey score, Cremoncini score, serum LH, LH/FSH ratio, total and free testosterone, dehydroepiandrosterone sulfate (DHEA-S), Δ-4-androstenedione, SHBG, prolactin, glucose/immunoreactive insulin (IRI) ratio, homeostatic model assessment (HOMA) index, and the resumption of regular menstrual cycles. Both the isoforms of inositol were effective in improving ovarian function and metabolism in patients with PCOS, although myo-inositol showed the most marked effect on the metabolic profile, whereas D-chiro-inositol reduced hyperandrogenism better.

Microwave endometrial ablation at a frequency of 2.45 GHz for menorrhagia: analysis of treatment results at a single facility.

AIM: We aimed to evaluate the efficacy of microwave endometrial ablation at a frequency of 2.45 GHz in women with menorrhagia. This method has been attracting attention as an alternative to hysterectomy in the treatment of functional and organic menorrhagia. MATERIAL AND METHODS: We performed microwave endometrial ablation in 103 women with menorrhagia between August 2007 and October 2012. All patients had completed child bearing. We evaluated the efficacy of microwave endometrial ablation using a visual analog scale for menorrhagia, dysmenorrhea, and patient satisfaction. We also evaluated the incidence of hypermenorrhea recurrence, amenorrhea, and procedure complications in relation to patients' clinical factors, such as the presence of myoma, adenomyosis, uterine size, and type of bleeding. RESULTS: A total of 76 patients completed the evaluation period. Excessive menstruation improved from a preoperative mean visual analog score of 10, to 1.9 after treatment. Dysmenorrhea improved from a mean score of 4.2, to 1.3, and patient satisfaction had a mean score of 9.0. Hemoglobin levels improved from 10.1 g/dL preoperatively to 12.5 g/dL postoperatively. Four patients experienced recurrence of excessive menstruation. No related clinical factors could be identified for recurrence risk or the occurrence of postoperative infection. A total of 26 patients (34.2%) became amenorrheic; these patients were less likely to have myomata, intramural myomata, and myomata larger than 5 cm. CONCLUSIONS: Microwave endometrial ablation at a frequency of 2.45 GHz is an effective and safe treatment. It should be considered as a standard treatment for conservative therapy-resistant menorrhagia.

Giant prolactinomas in women.

OBJECTIVE: To characterise distinctive clinical features of giant prolactinomas in women. DESIGN: A multicentre, retrospective case series and literature review. METHODS: We collected data from 15 female patients with a pituitary tumour larger than 4 cm and prolactin levels above 1000 µg/l and identified 19 similar cases from the literature; a gender-based comparison of the frequency and age distribution was obtained from a literature review. RESULTS: The initial PubMed search using the term 'giant prolactinomas' identified 125 patients (13 women) responding to the inclusion criteria. The female:male ratio was 1:9. Another six female patients were found by extending the literature search, while our own series added 15 patients. The median age at diagnosis was 44 years in women compared with 35 years in men (P<0.05). All cases diagnosed before the age of 15 years were boys. In women (n=34), we observed a minor peak incidence during the third decade of life and a major peak during the fifth decade. Amenorrhoea was a constant feature with seven cases of primary amenorrhoea. In eight women with onset of secondary amenorrhoea before the age of 40 years, the diagnosis was made 2-31 years later (median 9 years) and in all but one because of tumour pressure symptoms. The prolactin levels were above 10,000 µg/l in 15/34 and misdiagnosis due to 'hook effect' occurred in two of them. Eighteen patients were treated with cabergoline; standard doses (<2.0 mg/week) were able to normalise prolactin in only 4/18 patients, and 7/18 patients were resistant to weekly doses ranging from 3.0 to 7.0 mg. CONCLUSION: Giant prolactinomas are rare in women, often resistant to dopamine agonists and seem to be distributed in two age groups, with a larger late-onset peak.

Uterus transplantation from a deceased donor.

OBJECTIVE: To demonstrate the technique for uterus retrieval and transplantation from a multiorgan donor. DESIGN: Video presentation of our case report. The video uses animation to demonstrate the technique. Institutional Review Board (IRB) approval was obtained. SETTING: University hospital. PATIENT(S): A 21-year-old woman with complete müllerian agenesis. INTERVENTION(S): Uterus allotransplantation has been performed from a deceased donor. MAIN OUTCOME MEASURE(S): Acquirement of cyclic menstrual function. RESULT(S): This video demonstrates the technique for uterus retrieval, perfusion, and transplantation. The recipient patient has been monitored regularly for vascular flow, immunosuppression, and infection control since the operation. CONCLUSION(S): Uterus transplantation requires extensive evaluation of the recipient and donor by an experienced multidisciplinary transplantation team both pre- and postoperatively. It has major risks related to surgery, immunosuppression, and pregnancy. Uterus transplantation might be considered promising only after the birth of a near-term healthy baby.

Gonadatrophin suppression to prevent chemotherapy-induced ovarian damage: a randomized controlled trial.

OBJECTIVE: To estimate the effectiveness of gonadotropin-releasing hormone (GnRH) analogues cotreatment in preventing chemotherapy-induced amenorrhea in young breast cancer patients undergoing cyclophosphamide-based chemotherapy. METHODS: One hundred hormone-insensitive breast cancer participants (aged 18-40 years) were recruited from two university-affiliated oncology centers in Egypt. Opting for type of cotreatment was based on available timeframe until start of chemotherapy. Fifty women ready for early chemotherapy were randomized to receive either chemotherapy alone (arm I) or chemotherapy after downregulation (estradiol less than 50 pg/mL) by GnRH antagonist and agonist (arm II). Then, GnRH antagonist was discontinued and agonist was continued until the end of chemotherapy. When chemotherapy was to start later than 10 days after study inclusion, 50 women were randomized to receive either chemotherapy alone (arm III) or chemotherapy after downregulation with GnRH agonist (arm IV). Resumption of menstruation at 12 months after end of chemotherapy was the primary outcome. Postchemotherapy hormonal and ultrasound changes were secondary outcomes. RESULTS: Twelve months after termination of chemotherapy, there were no differences in menstruation resumption rates between GnRH-treated patients and control group individuals in either early (80% in arms I and II, risk ratio 1, 95% confidence interval 0.7-.32; P=1.00) or delayed chemotherapy groups (80% and 84% in arms III and IV, risk ratio 0.95, 95% confidence interval 0.73-1.235; P=.71). There were no differences in hormonal and ultrasound markers between GnRH analogue users and control group individuals. The use of GnRH analogue cotreatment did not predict independently the odds of menstruating at 12 months. CONCLUSION: GnRH analogue cotreatment does not offer a significant protective effect on ovarian function in patients treated by cyclophosphamide-based chemotherapy. CLINICAL TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry. www.anzctr.org.au, ACTRN12609001059257. LEVEL OF EVIDENCE: I.