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Leptin replacement in patients with leptin gene mutations improves hypogonadotropic hypogonadism. The effects of leptin replacement on luteinizing hormone (LH) secretion in patients with lipodystrophy are unknown.We examined nocturnal LH secretory dynamics on and off exogenous leptin therapy using a 2-period, nonrandomized study that included leptin-naïve and leptin-treated subjects with lipodystrophy.In period 1 (5 days) the leptin-treated group (n = 4) continued leptin; leptin was then withdrawn for the next 14 days (period 2). Leptin-naïve subjects (n = 8) were studied without leptin in period 1 and with leptin replacement in period 2. LH secretory dynamics were assessed (23:00-07:00 h, sampling every 10 min, analyzed by multiparameter deconvolution algorithm) at the end of each period.Mean (on vs. off: 5.0 ± 3.1 vs. 3.2 ± 1.3 IU/l, p = 0.04) and integrated LH concentrations (2,403 ± 1,495 vs. 1,534 ± 642 IU × l-1 × min-1, p = 0.04) were higher on leptin therapy. Leptin treatment increased burst mass (9.7± 15.4 vs. 7.0 ± 11.2 IU/l, p = 0.03) and tended to nonsignificantly increase LH burst frequency (0.77 ± 0.26 vs. 0.67 ± 0.24 h-1, p = 0.08). Consequently, leptin therapy increased the pulsatile production rate (64 ± 101 vs. 57 ± 73 IU × l-1 × 8 h-1, p = 0.01). On leptin, testosterone (507 ± 286 vs. 360 ± 174 ng/dl, p = 0.09) and estradiol levels (74 ± 36 vs. 29 ± 24 pg/ml, p = 0.01) were higher in males and females, respectively.Leptin increases spontaneous nocturnal LH secretion in patients with lipodystrophy. This is consistent with rodent and in vitro studies showing a direct stimulatory effect (hypothalamic, pituitary or both) of leptin on LH secretion. These novel findings may explicate some of the salutary effects of leptin therapy on the hypothalamic-pituitary-gonadal axis in lipodystrophy.

Introduction: Female genital chronic graft versus- host disease (fcGVHD) is an under- recognized and undertreated complication impacting quality of life of patients. It is reported to occur in a quarter of long-term female survivors. To determine clinical manifestations and their relation with severity of cGVHD in female patients with genital manifestations we prospectively analyzed a cohort of adult females who were enrolled on the cross-sectional cGVHD natural history study. Materials (or patients) and methods: A total of 130 consecutive female adult patients with cGVHD were assessed on this NCI protocol (clinicaltrials.gov identifier: NCT00331968) from 2004. to 2014. g. All patients were evaluated by an interdisciplinary team during four days visit. Detailed history, physical examination and laboratory analysis were done. Diagnosis of cGVHD was made according to NIH Consensus Group Criteria. NIH grading criteria was used to determine global cGVHD score as a measure of cGVHD severity. History related to genital issues, gynecology examination and special questionnaire related to demographic parameters, genital symptoms, hormonal therapy and sexual activity were performed. Diagnosis of genital cGVHD was made according to Stratton-Turner criteria. Descriptive statistics and Chi-square test for dichotomous variables were used in the statistical analysis. A P value o0, 05 was considered to be statistically significant. Results: Most frequent reason for allogeneic stem cell myeloic leukemia or myelodisplastic syndrome which were found in 66 (50.8%) patients. Myeloablative conditioning was performed in 70 (53, 8%) patients. In 105 patients (80, 8%) peripheral stem blood cells (PSBC) were used as stem source. Median age was 44.5 (range 18-70). Global cGVHD was severe in 97 (74, 6%) and moderate in 32 (24, 6%) patients. All patients had other organs involved. At the time of evaluation, 84 (64, 6%) patients had genital cGVHD. 53 (40, 8%) patients with genital cGVHD had severe genital changes (vaginal adhesions, shortened vagina). More than one third of patients with genital cGVHD (34.5%) did not have gynecological symptoms suggestive of genital cGVHD. There was no difference in age, frequency of myeloablative conditioning or cell source between patients with and without genital cGVHD. Patients with severe genital cGVHD were more likely to have severe global cGVHD score (P ¼ 0, 035). Conclusion: Genital cGVHD should be considered and gynecologic assessment performed in women with cGVHD even if they are asymptomatic. In this large series more than one third of women with genital cGHVD did not have any genital symptoms. Patients with severe global cGVHD stage are more likely to present with genital manifestations and deserve increased vigilance in evaluations.

Chronic Graft-Versus-Host Disease (cGVHD) is multisystemic disease and major complication after allogeneic hematopoietic cell transplantation. Although genital cGVHD is one of the frequent manifestations of cGVHD, it is still not well investigated. The goal of this study was to assess prevalence of genital cGVHD and genital human papillomavirus infection (HPV) in female patients with cGVHD. A multidiscipinary cGVHD team was established at the University Hospital Center Zagreb in collaboration with the National Cancer Institute, National Institutes of Health. From 2013 to 2014, eight adult female patients were examined by a gynecologist skilled in genital cGVHD assessments as part of the protocol "Clinical and biological factors determining severity and activity of cGVHD after allogeneic hematopoietic cell transplantation". NIH grading criteria was used to determine global cGVHD score as a measure of cGVHD severity. An extensive hystory, physical and laboratory analyses were obtained at study entry. In all patients, cervical cytology, human papillomavirus testing, vaginal swab for bacterial and fungal colonisation were done. Diagnosis of genital cGVHD was made using Stratton-Turner criteria. HPV were detected by polymerase chain reaction (PCR). Blood was collected to determine the level of luteinizing hormone, follicle stimulating hormone and estradiol in order to define menopause. Three patients (37.5%) underwent myeloablative conditioning. In 5 patients (62.5%) peripheral stem blood cells (PSBC) were used as stem source. Median age was 43.5 (range 23-57). Global cGVHD was severe in 6/8 (75%) and moderate in 2/8 (25%) patients. All patients had other organs involved. At the time of evaluation, 4/8 (50%) patients had genital cGVHD. All 4 patients with genital cGVHD had severe genital changes (vaginal adhesions, shortened vagina). Gynecological symptoms suggestive of genital cGVHD were reported by all affected patients. Cervical cytology was normal in 8/8 (100%) patients. HPV infection was observed in 3/8 (37, 5%) patients, two without genital cGVHD and one with genital cGVHD. Menopausal status was noted in 7/8 (88%) patients. All menopausal patients without genital cGVHD reported dryness and had signs of urogenital atrophy. One patient with vaginal shortening to depth of 5 cm suggesting genital cGVHD but who lacked signs of active genital cGVHD was initiated on dilator therapy. Topical estrogen cream and 4% topical lidocaine was applied to the dilator to reduce pain during dilation. In two months, the vaginal depth was successfully increased from 5 to 12 cm. Conclusion: In this small series of women with global cGVHD severity classified as moderate to severe, the prevalence of severe vaginal genital cGVHD was 50%. All women with genital cGHVD had vaginal adhesions or shortened vagina. Dilator therapy with topical estrogen cream and topical 4% lidocaine successfully improved vaginal shortening attributed to cGVHD in a patient without signs of active genital cGVHD. Patient without genital cGVHD who reported symptoms of vulvar/vaginal dryness and with signs of urogenital atrophy should be treated with topical estrogen. HPV infection is frequently present in women with cGVHD. Genital cGVHD should be considered and gynecologic assessment with genital HPV and cervical cytology testing performed in all women with cGVHD. Disclosure of Interest: None declared.

Hematopoietic stem cell transplantation (HSCT) plays a central role in patients with malignant and, increasingly, nonmalignant conditions. As the number of transplants increases and the survival rate improves, long-term complications are important to recognize and treat to maintain quality of life. Sexual dysfunction is a commonly described but relatively often underestimated complication after HSCT. Conditioning regimens, generalized or genital graft-versus-host disease, medications, and cardiovascular complications as well as psychosocial problems are known to contribute significantly to physical and psychological sexual dysfunction. Moreover, it is often a difficult topic for patients, their significant others, and health care providers to discuss. Early recognition and management of sexual dysfunction after HSCT can lead to improved quality of life and outcomes for patients and their partners. This review focuses on the risk factors for and treatment of sexual dysfunction after transplantation and provides guidance concerning how to approach and manage a patient with sexual dysfunction after HSCT.

Between 2004 and 2010, 189 adult patients were enrolled on the National Cancer Institute's cross-sectional chronic graft-versus-host disease (cGVHD) natural history study. Patients were evaluated by multiple disease scales and outcome measures, including the 2005 National Institutes of Health (NIH) Consensus Project cGVHD severity scores. The purpose of this study was to assess the validity of the NIH scoring variables as determinants of disease severity in severely affected patients in efforts to standardize clinician evaluation and staging of cGVHD. Out of 189 patients enrolled, 125 met the criteria for severe cGVHD on the NIH global score, 62 of whom had moderate disease, with a median of 4 (range, 1-8) involved organs. Clinician-assigned average NIH organ score and the corresponding organ scores assigned by subspecialists were highly correlated (r = 0.64). NIH global severity scores showed significant associations with nearly all functional and quality of life outcome measures, including the Lee Symptom Scale, Short Form-36 Physical Component Scale, 2-minute walk, grip strength, range of motion, and Human Activity Profile. Joint/fascia, skin, and lung involvement affected function and quality of life most significantly and showed the greatest correlation with outcome measures. The final Cox model with factors jointly predictive for survival included the time from cGVHD diagnosis (>49 versus ≤49 months, hazard ratio [HR] = 0.23 ; P = .0011), absolute eosinophil count at the time of NIH evaluation (0-0.5 versus >0.5 cells/μL, HR = 3.95 ; P = .0006), and NIH lung score (3 versus 0-2, HR = 11.02 ; P < .0001). These results demonstrate that NIH organs and global severity scores are reliable measures of cGVHD disease burden. The strong association with subspecialist evaluation suggests that NIH organ and global severity scores are appropriate for clinical and research assessments, and may serve as a surrogate for more complex subspecialist examinations. In this population of severely affected patients, NIH lung score is the strongest predictor of poor overall survival, both alone and after adjustment for other important factors.

Female long-term survivors of allogeneic hematopoietic stem cell transplantation (allo-HSCT) incur a significant burden of late effects. Genital graft-versus-host disease (GVHD), human papillomavirus (HPV) reactivation, ovarian failure and infertility, sexual dysfunction, and osteoporosis are concerns that can significantly impact quality of life. This review examines the risk, pathogenesis, clinical presentation, and implications of these common complications. Recommendations are provided for evaluation and management of these late effects and other obstetric and gynecologic issues that may arise in this patient population.

Barrier contraceptive devices like the cervical cap and diaphragm and menstrual collecting devices may block menstrual flow, increase retrograde menstruation, and thus theoretically increase the likelihood of developing endometriosis or adenomyosis. We describe the case of a woman with a prior tubal ligation who after four years of regular use of the Keeper, a menstrual collecting device, developed endometriosis and adenomyosis.