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

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

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.

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.

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.

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.

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.

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.

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.

Ovarian function is preserved in women with severe systemic lupus erythematosus after a 6-month course of cyclophosphamide followed by mycophenolate mofetil.

OBJECTIVE: To evaluate whether a short duration treatment with cyclophosphamide (CYC) followed by mycophenolate mofetil (MMF) is associated with preservation of the ovarian function in female patients with systemic lupus erythematosus (SLE). METHODS: We retrospectively evaluated 61 premenopausal women with SLE treated for lupus nephritis (n=58), autoimmune hemolytic anemia (n=1) and central nervous system involvement (n=2). Thirty-nine patients received prolonged treatment with 1 g/m2 intravenous (IV) CYC pulses (group I). 22 patients received 5-7 monthly 1 g/m2 IV CYC pulses and afterwards 2 g/day MMF (group II). RESULTS: Disease activity was equally controlled using either regimen (p=0.76 and p=0.31 for disease remission and relapse respectively). Amenorrhea developed in 56% of women in group I (n=22) and 14% in group II (n=3) (p=0.01), whereas sustained amenorrhea developed in 51% (n=20) of women in group I versus 4% (n=1) in group II (p=0.05). Most women with amenorrhea in group I (86%) did not resume menses after the cessation of therapy versus one woman (33%) in group II. In logistic regression, group I had a 4-fold higher risk of amenorrhea and 5-fold higher risk of sustained amenorrhea compared to group II (p=0.001 and p=0.009 respectively). Age (p<0.001), cumulative CYC dose (p=0.001) and anti-Ro antibodies (p=0.002) were significant in terms of amenorrhea, while sustained amenorrhea was significantly associated with the patient age (p=0.026). CONCLUSION: We suggest that treatment with MMF following 5-7 IV pulses of CYC is an effective mean to control disease activity and preserve ovarian function in premenopausal women with SLE.

[Unexplained weight gain in a 41-year-old woman]. / Unklare Gewichtszunahme bei einer 41-jährigen Frau.

A 41-year-old female was admitted to our clinic due to weight gain and facial edema. The patient also reported hair loss, amenorrhea and the formation of striae. The laboratory diagnostics ensured the diagnosis of Cushing's syndrome. Unfortunately, the patient was among the 5-10% of patients in whom neither laboratory testing nor imaging revealed the source of the cortisol excess. Due to the dramatic decrease of her general condition, and the appearance of hypertension and diabetes mellitus we chose to refer the patient to bilateral minimally invasive adrenalectomy. The advantage of this therapeutic approach is, that it is a definitive treatment that provides immediate control of hypercortisolism. As disadvantage, the resultant permanent hypoadrenalism requires a lifelong glucocorticoid and mineralocorticoid replacement therapy. Furthermore, given that the problem was caused by occult pituitary microadenoma, Nelson's syndrome has to be considered. As only one adrenal could be excised due to technical reasons, the underlying pathology is thus not solved. In spite of this, the patient's general condition improved dramatically without need for replacement therapy. As the mortality of patients with persistent moderate hypercortisolism is increased 3,8- to 5 fold, mainly due to cardiovascular reasons, thorough surveillance for signs of recurrence is mandatory to be ready for quick intervention.

[Musculoskeletal rehabilitation and bone. Abnormal bone metabolism in female elite athletes].

Recently, female athletes are particularly well, the other hand, many athletes suffer from amenorrhea due to excessive training. Especially, in sports with weight restrictions, they suffer from "Female athlete triad" , eating disorders, amenorrhea and osteoporosis. Amenorrhea is nothing else than a lack of estrogen, action on bone resorption and promote bone formation, by neglect this, it lead to osteoporosis and a stress fracture, and they would often give up their career as elite athletes. So we should consider it as serious sports injury. The problems of amenorrhea is should be recognized as a deficiency of estrogen. A Case of amenorrhea in female athletes, it is necessary to consider the hormone replacement therapy based on the appropriate diagnosis. However, it is important to start the management of body fat and body weight and strength of exercises since adolescent for the prevention the amenorrhea.

[Menstrual dysfunction in anorexia nervosa]. / Zaburzenia miesiaczkowania w jadlowstrecie psychicznym.

One of the symptoms of anorexia nervosa (a.n.) is cessation of pubescence or secondary amenorrhea. Their origin in anorexia nervosa is multifactorial, partly resulting from starvation-induced hipogonadism. Amenorrhea in a.n. may persist despite weight recovery and is often related to osteoporosis. The authors' present causes of amenorrhea and its persisting in a.n., pointing to the factors influencing prognosis according to resumption of menses. They also review reports of hormonal replacement therapy in this group of 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.

The young female athlete.

Participation of adolescents and young women in strenuous sports activity may lead to various metabolic and psychological derangements of clinical relevance to the endocrinologist. The most common manifestations encountered in practice are primary and secondary amenorrhea, reduced bone mineral density and eating disorders. The occurrence of all three together has been named "the athletic triad". The underlying hormonal drivers that lead to some of these manifestations are the reduced leptin level as well as the persistent low grade stress response commonly observed in such females. "Exercise-related female reproductive dysfunction" (ERFRD), can possibly include short-term (infertility) and long-term (osteoporosis) consequences. Functional hypothalamic amenorrhea, a manifestation of ERFRD in adolescence, is an integrated response to the combination of excessive physical and emotional stress, exercise, and/or reduced food intake characterized by decreased endogenous GNRH secretion. The primary aim of treating these athletes should be the prevention of the development of any component of the triad as well as the whole complex by educating athletes, trainers, parents and health care professionals about proper nutrition and safe training. The long term prognosis is good. However, significant long term morbidity may affect these young women later in life.

[The role of a pediatric endocrinologist in diagnostics and therapeutic management of anorexia nervosa--own experiences and review of literature]. / Rola endokrynologa dzieciecego w diagnostyce i leczeniu jadlowstretu psychicznego--doswiadczenia wlasne i przeglad pismiennictwa.

INTRODUCTION: Anorexia nervosa and bulimia nervosa are counted among psychosomatic diseases, whose incidence has been rapidly increasing in the last decades. To date, the etiology, diagnostic and therapeutic management of eating disorders have not been uniformly determined. The objective of the study is determination of the role of a pediatric endocrinologist in diagnostics and management of eating disorders. MATERIAL: In the years 1992-2007 in Department of Pediatric and Adolescent Endocrinology Chair of Pediatrics, Polish-American Institute of Pediatrics, Collegium Medicum, Jagiellonian University in Krakow, Poland were hospitalized 164 patients with suspected anorexia nervosa, aged 9-20 years, 150 girls, and 14 boys. All girls were included in psychological and dietetic treatment. Additionally, in group of 36 girls, the 3-years observation of bone mineralization changes was performed. METHODS: The indications for hospitalization included the assessment of nutritional status, particularly electrolyte imbalance, cardiovascular complications and nutritional treatment. II. Procedure included on department: 1) Correction of general children's state. 2) Monitoring of cardiovascular system disorders. 3) Nutritional treatment. 4) Differential diagnosis. III. Prevention and treatment of late complications was performed in group of 36 girls. In this group, every 6 months were evaluated: body mass index, duration of secondary amenorrhea, serum sex hormone, IGF-I and cortisol levels and 24-hour urine cortisol. Spine densitometry in the AP projection was performed every 12 months, using a Lunar unit (DEXA). The pharmacological treatment of osteoporosis was introduced in girls with duration of secondary amenorrhea lasted for more than 6 months, with decreased bone mineralization BMD < (-) 1SD and body mass deficit < 20%. 16 girls which did not presented disorders of bone mineralization, or refused treatment have not got the pharmacological treatment, while in 20 girls the pharmacological therapy (calcium and vitamin D3 supplementation and hormonal treatment - Estraderm TTS and Provera 5 mg) was provided. RESULTS: Anorexia nervosa was diagnosed in 150 cases, bulimia in 6 cases, in 2 children was diagnosed celiac disease, in 2 patients adrenal insufficiency, in 1 girl myasthenia, in 1 girl diabetes mellitus type 1, in 1 boy hypothalamo-pituitary tumor and in 1 boy psychosis was diagnosed. The nutritional improvement was evaluated in group of 36 girls, which continued treatment in time 3 years. At the beginning of the observation period the mean value of the body mass index (BMI) was 15.95 kg/m2, and after 36 months of the treatment the mean BMI value was 20 kg/m2. Before the treatment one patient was still menstruated despite her body mass loss, 8 girls were pre-menarche, and the remaining 27 patients had secondary amenorrhea of the mean duration of 11.14 months. In the initial period of the follow-up, all the anorectic patients demonstrated a decreased bone mineral density. Before treatment the median Z score in the entire experimental group was (-)1,2 SD whereas after 3 years of treatment value of Z score decreased by 0,5 SD in group of 16 girls without the pharmacological treatment and increased by 0,5 SD in 20 girls on pharmacological treatment. The significant, negative correlation between secondary amenorrhea and Z score value was observed. CONCLUSIONS: The role of a pediatrician in therapeutic management of eating disorders is intervention in life-threatening conditions, treatment of acute complications, differential diagnosis, nutritional treatment, prevention and management of late complications. Because of etiology and special way of treatment the management of anorexia nervosa should have been taken by psychiatrist. The duty of endocrinologists and gynecologists is the late complications treatment, such as an amenorrhea and osteoporosis.

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.

Cancer and fertility preservation: fertility preservation in breast cancer patients.

Aggressive chemotherapy has improved the life expectancy for reproductive-age women with breast cancer, but it often causes infertility or premature ovarian failure due to destruction of the ovarian reserve. Many questions concerning fertility preservation in breast cancer patients remain unanswered--for example, whether fertility preservation methods interfere with chemotherapy, and whether subsequent pregnancy has negative effects on the prognosis. Fertility preservation is a critical factor in decision-making for younger breast cancer patients, however, and clinicians should address this. The present article reviews the incidence of chemotherapy-induced amenorrhea, and discusses fertility-preservation options and the prognosis for patients who become pregnant after breast cancer.

Treatment goal weight in adolescents with anorexia nervosa: use of BMI percentiles.

OBJECTIVE: There is a lack of consensus as to how to determine treatment goal weight in the growing adolescent with anorexia nervosa (AN). Resumption of menses (ROM) is an indicator of biological health and weight at ROM can be used as a treatment goal weight. This study determined the BMI percentile for age at which ROM occurs. METHOD: A secondary analysis of a prospective cohort study examining 56 adolescent females with AN, aged 12-19 years, followed every 3 months until ROM. BMI percentiles for age and gender at ROM were determined using the nutrition module of Epi Info 2002. RESULTS: At 1-year follow-up, 36 participants (64.3%) resumed menses and 20 (35.7%) remained amenorrheic. Mean BMI percentile at ROM was 27.1 (95% CI = 20.0-34.2). Fifty percent of participants who resumed menses, did so at a BMI percentile between the 14th and 39th percentile. CONCLUSION: A BMI percentile range of 14th-39th percentile can be used to assign a treatment goal weight, with adjustments for prior weight, stage of pubertal development, and anticipated growth.