Menopausal symptoms and quality of life in female survivors treated with hematopoietic stem cell transplantation.

Objectives: To assess the severity of menopausal symptoms and the correlation among different quality of life questionnaires and compare the quality of life of patients who underwent hematopoietic stem cell transplantation (HSCT) for hematological disorders with the norm group in order to facilitate personalized and directed therapeutic intervention for patients. Methods: We recruited women who had premature ovarian failure (POF) after HSCT for hematologic diseases in the gynecological endocrinology outpatient clinic of Peking University People's Hospital. Women with HSCT were included in the study if they had 6 months of spontaneous amenorrhea with serum follicle-stimulating hormone levels greater than 40 mIU/mL taken 4 weeks apart. The patients who had other causes of POF were excluded. During the survey, all women were required to fill out the questionnaires [Quality of Life Questionnaire (MENQOL), Generalized Anxiety Disorder-7 (GAD-7), Patient Health Questionnaire-9 (PHQ-9), and 36-item Short-Form (SF-36)] online. We analyzed the severity of menopausal symptoms, anxiety, and depression in Participants. In addition, differences on the SF-36 scale scores between the study group and norm groups were examined. Results: In total, 227 (93.41%) patients completed the survey and were analyzed. The severity of all symptoms is "none and mild" in MRS, MENQOL, GAD-7, and PHQ-9. On the MRS, the most common symptoms were irritability, physical and mental exhaustion, and sleep problems. The severest symptoms were sexual problems (53, 73.82%), followed by sleep problems (44, 19.38%) and mental and physical exhaustion (39, 17.18%). In the MENQOL, the most common symptoms were psychosocial and physical symptoms. The severest symptoms were sexual symptoms (35, 48.75%) followed by psychosocial symptoms (23, 10.13%). Moderate-severe scores were shown in 11.89% (27) and 18.72% (42) cases in the GAD-7 and PHQ-9, respectively. Based on SF-36, in comparison with the norm group, the HSCT participants had higher vitality scores and lower role physical, physical functioning, and role emotional scores aged 18-45. In addition, the HSCT participants had lower mental health scores aged 18-25, and lower general health scores aged 25-45. No strong correlation was observed between questionnaires in our study. Conclusion: Overall, menopausal symptoms are milder in female patients after HSCT. There is no single scale that comprehensively assesses the patient's quality of life after HSCT. We need to assess the severity of various symptoms in patients using different scales.

Protective Effect and Mechanism of Kuntai Capsule on Angiotensin II -Induced Hypertension in Ovariectomized Rats.

OBJECTIVE: To explore the protective effect and mechanism of Kuntai (KT) Capsule on angiotensin II (Ang II)-induced hypertension in ovariectomized (OVX) rats. METHODS: Fifty-four rats were randomly divided into 6 groups according to a random number table, 9 in each group: control, OVX sham+Ang II, OVX, OVX+Ang II, OVX+Ang II +E2, and OVX+Ang II +KT. OVX rats model was constructed by retroperitoneal bilateral ovariectomy. After 4 weeks of pretreatment with KT Capsule [0.8 g/(kg·d) and 17- ß -estradiol (E2, 1.2 mg/(kg·d)] respectively, Ang II was injected into a micro-osmotic pump with a syringe to establish a hypertensive rat model. Blood pressure of rat tail artery was measured in a wake state of rats using a non-invasive sphygmomanometer. Blood pressure changes were compared between the intervention groups (OVX+Ang II +KT, OVX+Ang II +E2) and the negative control group (OVX+Ang II). Serum malondialdehyde (MDA) level and superoxide dismutase (SOD) activity were detected respectively. The expressions of oxidative stress-related protein superoxide dismutase2 (SOD2) and anti-thioredoxin (TRX), autophagy marker protein [beclin1, light chain (LC) 3 II/I ratio and autophagy canonical pathway protein phosphatidylinositol 3-kinase (PI3K)/serine/threonine kinase (AKT)-mammalian target of rapamycin (mTOR)] were evaluated by Western blotting. RESULTS: Compared with the OVX+Ang II group, the systolic blood pressure of OVX+Ang II +KT group was significantly lowered (P<0.05) but not the diastolic blood pressure. Besides, SOD2 and TRX protein levels in mycardial tissues were significantly reduced in the OVX+Ang II +KT group compared with the OVX+Ang II group (P<0.05). Oxidative stress serum markers MDA and SOD were down- and up-regulated in the OVX+Ang II +KT group, respectively (P<0.05). Compared with OVX+Ang II group, the levels of cardiac proteins beclin-1 and LC3II/LC3 I in OVX+Ang II +KT group were also up-regulated (P<0.05), and the expression levels of p-PI3K, p-AKT and mTOR protein were down-regulated (P<0.05). CONCLUSION: KT could protect blood pressure of Ang II-induced OVX rats by inhibiting oxidative stress and up-regulating protective autophagy.

Gynecological complications in long-term survivors after allogeneic hematopoietic cell transplantation-a single-center real-life cross-sectional study.

Background and objectives: Hematopoietic stem cell transplantation (HCT) is a treatment for hematopoietic diseases. However, most cured female patients may suffer from premature ovarian insufficiency (POI) after HCT, which is mainly caused by the pre-HCT conditioning regimen. Hence, this study aims to explore the impact of HCT treatment on reproductive and ovarian functions in female survivors. Methods: A total of 55 female participants under the age of 40, who underwent HCT and met the inclusion criteria were enrolled. Data related to blood disease, menstruation, and fertility in the 3 years following HCT were collected. Results: The involved patients received transplantation at different age stages, ranging from 8 to 37. All patients, except those with aplastic anemia (AA; 5/55), received a myeloablative conditioning regimen, usually modified total body irradiation/cyclophosphamide (TBI/Cy; 25/55) or modified Busulfan/cyclophosphamide (Bu/Cy; 23/55). Among women (42/55) who menstruated before HCT, 16.67% (7/42) had a spontaneous menstrual relapse and 83.3% (35/42) had amenorrhea after HCT. 72.7% (40/55) could be regarded as having POI. This proportion included 100% (25/25) of women aged 21-40 at the time of HCT, 62.5% (15/24) of those aged 11-20, and 0% (0/6) of those ≤10 years old. Patients with AML were more likely to have POI (95.7%). Patients aged ≤10 years (0%) or 11-20 years (16.7%) at the time of HCT were less likely to have moderate to severe menopause than those 21-40 years old (44%). Conclusion: The prevalence of POI following HCT was high and POI was associated with age, conditioning regimen, and type of blood disease.

Assessment of menopausal symptoms and quality of life in women with premature ovarian failure after hematopoietic stem-cell transplantation for hematologic diseases.

OBJECTIVE: This study aimed to evaluate and compare menopausal symptoms and quality of life between women with premature ovarian failure who underwent hematopoietic stem-cell transplantation (HSCT) for hematologic diseases and naturally menopausal women. METHODS: This observational study enrolled 415 women (215 HSCT women and 200 naturally menopausal women as control group) from June 2017 to November 2019 in the menopause clinic of Peking University People's Hospital. Menopausal symptoms and quality of life were evaluated using the modified Kupperman index (KI), menopause rating scale (MRS), and menopause quality of life questionnaire. RESULTS: The total KI and MRS scores were 12.53 ±â€Š8.27 and 7.69 ±â€Š6.50 in the HSCT group and 21.57 ±â€Š9.23 and 12.05 ±â€Š6.70 in the control group, respectively (P < 0.05). The scores related to sexual problems and vaginal dryness were 1.20 ±â€Š1.24 and 1.07 ±â€Š1.24 in the HSCT group and 1.15 ±â€Š1.01 and 1.01 ±â€Š1.01 in the control group, respectively (P > 0.05). Age was a risk factor for menopausal symptoms (odds ratio 1.70, 95% confidence interval 1.01-1.12). The main reasons for consultations in the HSCT group were amenorrhea and infertility (76.74%). CONCLUSIONS: Compared with naturally menopausal women with the same number of years since menopause, the MRS and KI scores of women with premature ovarian failure who underwent HSCT showed milder symptoms. The MRS may be a better alternative to reflect the severity of menopausal symptoms. Age was a risk factor for menopausal symptoms. Oncofertility counseling should be initiated as early as possible before the start of treatment.

Response to the Svingen Comments on Li et al. Effects of in Utero Exposure to Dicyclohexyl Phthalate on Rat Fetal Leydig Cells. Int. J. Environ. Res. Public Health, 2016, 13, 246.

Referring to the comments of Svingen [1] on our latest publication about Effects of in utero Exposure to Dicyclohexyl Phthalate on Rat Fetal Leydig Cells [2], we would like to give some comments.[...].

Effects of in Utero Exposure to Dicyclohexyl Phthalate on Rat Fetal Leydig Cells.

Dicyclohexyl phthalate (DCHP) is one of the phthalate plasticizers. The objective of the present study was to investigate the effects of DCHP on fetal Leydig cell distribution and function as well as testis development. Female pregnant Sprague Dawley dams orally received vehicle (corn oil, control) or DCHP (10, 100, and 500 mg/kg/day) from gestational day (GD) 12 to GD 21. At GD 21.5, testicular testosterone production, fetal Leydig cell number and distribution, testicular gene and protein expression levels were examined. DCHP administration produced a dose-dependent increase of the incidence of multinucleated gonocytes at ≥ 100 mg/kg. DCHP dose-dependently increased abnormal fetal Leydig cell aggregation and decreased fetal Leydig cell size, cytoplasmic size, and nuclear size at ≥ 10 mg/kg. DCHP reduced the expression levels of steroidogenesis-related genes (including Star, Hsd3b1, and Hsd17b3) and testis-descent related gene Insl3 as well as protein levels of 3ß-hydroxysteroid dehydrogenase 1 (HSD3B1) and insulin-like 3 (INSL3) at ≥ 10 mg/kg. DCHP significantly inhibited testicular testosterone levels at ≥ 100 mg/kg. The results indicate that in utero exposure to DCHP affects the expression levels of fetal Leydig cell steroidogenic genes and results in the occurrence of multinucleated gonocytes and Leydig cell aggregation.

Inutero exposure to diisononyl phthalate caused testicular dysgenesis of rat fetal testis.

Diisononyl phthalate (DINP) is a synthetic material that has been widely used as a substitute for other plasticizers prohibited due to reproductive toxicity in consumer products. Some phthalates have been associated with testicular dysgenesis syndrome in male fetus when female pregnant dams were exposed to them. The present study investigated effects of DINP on fetal Leydig cell function and testis development. Female pregnant Sprague Dawley rats received control vehicle (corn oil) or DINP (10, 100, 500, and 1000 mg/kg) by oral gavage from gestational day (GD) 12 to 21. At GD 21.5, testicular testosterone production, fetal Leydig cell numbers and distribution, testicular gene and protein expression levels were examined. DINP showed dose-dependent increase of fetal Leydig cell aggregation with the low observed adverse-effect level (LOAEL) of 10 mg/kg and multinucleated gonocyte with LOAEL of 100 mg/kg. At 10 mg/kg, DINP also significantly increased fetal Leydig cell size, but inhibited insulin-like 3 and 3ß-hydroxysteroid dehydrogenase gene expression and protein levels. DINP inhibited testicular testosterone levels at 1000 mg/kg. The results indicate that in utero exposure to DINP affects the expression levels of some fetal Leydig cell steroidogenic genes, gonocyte multinucleation and Leydig cell aggregation.

Time-course changes of steroidogenic gene expression and steroidogenesis of rat Leydig cells after acute immobilization stress.

Leydig cells secrete testosterone, which is essential for male fertility and reproductive health. Stress increases the secretion of glucocorticoid (corticosterone, CORT; in rats), which decreases circulating testosterone levels in part through a direct action by binding to the glucocorticoid receptors (NR3C1) in Leydig cells. The intratesticular CORT level is dependent on oxidative inactivation of glucocorticoid by 11ß-hydroxysteroid dehydrogenase 1 (HSD11B1) in Leydig cells. In the present study, we investigated the time-course changes of steroidogenic gene expression levels after acute immobilization stress in rats. The plasma CORT levels were significantly increased 0.5, 1, 3 and 6 h after immobilization stress, while plasma testosterone levels were significantly reduced 3 and 6 h, after stress and luteinizing hormone (LH) did not change. Immobilization stress caused the down-regulation of Scarb1, Star and Cyp17a1 expression levels in the rat testis starting at the first hour of stress, ahead of the significant decreases of plasma testosterone levels. Other mRNA levels, including Cyp11a1, Hsd3b1 and Hsd17b3, began to decline after 3 h. Hsd11b1 and Nos2 mRNA levels did not change during the course of stress. Administration of glucocorticoid antagonist RU486 significantly restored plasma testosterone levels. In conclusion, Scarb1, Star and Cyp17a1 expression levels are more sensitive to acute stress, and acute immobilization stress causes the decline of the steroidogenic pathway via elevating the levels of glucocorticoid, which binds to NR3C1 in Leydig cells to inhibit steroidogenic gene expression.