Genitourinary symptoms and sexual function in women with primary ovarian insufficiency.

OBJECTIVE: There are limited studies on urogenital symptoms in women who experience menopause before the age of 40 years due to primary ovarian insufficiency (POI) or bilateral oophorectomy (surgical POI). This study aimed to compare the urogenital symptoms, including sexuality, of women with POI to those without the condition. METHODS: This cross-sectional study conducted was in seven Latin American countries, in which postmenopausal women (with POI and non-POI) were surveyed with a general questionnaire, the Menopause Rating Scale (MRS) and the six-item Female Sexual Function Index (FSFI-6). The association of premature menopause with more urogenital symptoms and lower sexual function was evaluated with logistic regression analysis. RESULTS: Women with POI experience more urogenital symptoms (MRS urogenital score: 3.54 ± 3.16 vs. 3.15 ± 2.89, p < 0.05) and have lower sexual function (total FSFI-6 score: 13.71 ± 7.55 vs. 14.77 ± 7.57 p < 0.05) than women who experience menopause at a normal age range. There were no significant differences in symptoms when comparing women based on the type of POI (idiopathic or surgical). After adjusting for covariates, our logistic regression model determined that POI is associated with more urogenital symptoms (odds ratio [OR]: 1.38, 95% confidence interval [CI] 1.06-1.80) and lower sexual function (OR: 1.67, 95% CI 1.25-2.25). CONCLUSION: POI, whether idiopathic or secondary to bilateral oophorectomy, is associated with symptoms that affect vaginal and sexual health.

Association of bilateral oophorectomy and menopause hormone therapy with mild cognitive impairment: the REDLINC X study.

BACKGROUND: Dementia is a major public health problem. Estrogen is a regulator of the central nervous system and its deficit could be involved in cognitive decline in older women. OBJECTIVE: This study aimed to evaluate the association of bilateral oophorectomy, menopause hormone therapy (MHT) and other factors on mild cognitive impairment (MCI). METHOD: The case-control study included 941 otherwise healthy postmenopausal women aged 60 years and over from six Latin American countries. Personal and family data were recorded and MCI was assessed using the Montreal Cognitive Assessment test (MoCA). RESULTS: Average age, years of education and body mass index were 66.1 ± 5.8 years, 12.4 ± 5.0 years and 26.0 ± 4.3 kg/m2, respectively. A total of 30.2% had undergone bilateral oophorectomy and 40.3% had used MHT. A total of 232 women (24.7%) had MCI. The prevalence of MCI was higher in women with intact ovaries and non-MHT users as compared to MHT users (29.3% vs. 11.7% [odds ratio (OR) 0.32; 95% confidence interval (CI) 0.20-0.51]). Among oophorectomized women, MCI prevalence was higher among non-MHT users as compared to MHT users (45.2% vs. 12.8% [OR 0.18; 95% CI 0.10-0.32]). Logistic regression analysis determined that the variables associated with MCI were age >65 years (OR 1.69; 95% CI 1.20-2.38), parity (having >2 children; OR 1.69; 95% CI 1.21-2.37), bilateral oophorectomy (OR 1.56; 95% CI 1.09-2.24), hypertension (OR 1.41; 95% CI 1.01-1.96), being sexually active (OR 0.56; 95% CI 0.40-0.79), education >12 years (OR 0.46; 95% CI 0.32-0.65) and MHT use (OR 0.31; 95% CI 0.21-0.46). CONCLUSION: Age, parity, bilateral oophorectomy and hypertension are independent factors associated with MCI; contrary to this, higher educational level, maintaining sexual activity and using MHT are protective factors.

Gender differences in the prevalence of vitamin D deficiency in a southern Latin American country: a pilot study.

Aim: This study aimed to study the prevalence of vitamin D deficiency, assessing the influence of sex, age, and season of the year.Methods: A cross-sectional study was conducted with 1329 healthy subjects (668 women and 661 men) aged 18-89 years in Santiago, Chile. Age (years), body mass index, medical history, working status, sex, and date of blood sample were collected.Results: Men were slightly older than women (53.1 ± 18.2 vs. 50.0 ± 15.6 years; p < 0.01) and a higher percentage worked outside the home (73.1% vs. 51.9%, p < 0.001). The mean serum concentration of 25-hydroxyvitamin D (25(OH)-D) was 23.3 ± 9.3 ng/ml in women and 20.9 ± 9.5 ng/ml in men (p < 0.001). The levels of 25(OH)-D by season were 26.7 ± 9.0, 23.6 ± 9.7, 19.4 ± 8.5, and 19.1 ± 9.5 ng/ml (for summer, fall, winter, and spring, respectively; p < 0.05). The prevalence of vitamin D deficiency increases with age, rising from 36.5% under 40 years to 48.0% over 60 years (p < 0.004). Male sex, winter and spring, and age showed negative correlation with levels of 25(OH)-D (p < 0.05). Multivariate linear regression showed a final model that incorporates: age (coefficient: -0.06; 95% confidence interval [CI]: -0.09 to -0.03; p < 0.001), male sex (coefficient: -2.00; 95% CI: -2.96 to -1.05; p < 0.001), summer (coefficient: 7.30; 95% CI: 6.17 to 8.43; p < 0.001), and fall (coefficient: 4.27; 95% CI: 3.04 to 5.50; p < 0.001).Conclusions: Vitamin D deficiency is more prevalent in men than in women, in the elderly, and during the winter and spring seasons.

Menopausal symptoms are associated with non-adherence to highly active antiretroviral therapy in human immunodeficiency virus-infected middle-aged women.

Objective: This study aimed to evaluate the association between the intensity of menopausal symptoms and highly active antiretroviral therapy (HAART) adherence in middle-aged women with human immunodeficiency virus (HIV) infection.Methods: In this cross-sectional study, 313 Peruvian women with HIV infection (age 40-59 years) were surveyed and classified as adherent or non-adherent to HAART based on the Antiretroviral Treatment Adherence Evaluation Questionnaire. The intensity of menopausal symptoms was assessed with the Menopause Rating Scale, and categorized as none, mild, moderate, and/or severe. Age, sexual orientation, used HAART scheme, time since HIV diagnosis, menopausal status, risk of depression, and presence of comorbidities were also assessed. Poisson generalized linear models with robust variance were performed in order to estimate crude prevalence ratios (PRs) and adjusted PRs using statistical (a1PR) and epidemiological criteria (a2PR).Results: A total of 19.9%, 32.6%, and 15.0% of all women presented mild, moderate, and severe menopausal symptoms, respectively. Overall, 70.6% women were non-adherent to HAART. The probability of non-adherence was higher in women with mild, moderate, and severe symptoms as compared to asymptomatic women in the non-adjusted model (PR: 1.79, 95% confidence interval [CI]: 1.39-2.29; PR: 1.76, 95% CI: 1.38-2.23; and PR: 2.07, 95% CI: 1.64-2.61, respectively) and the adjusted model.Conclusion: The severity of menopausal symptoms was associated with HAART non-adherence in HIV-infected middle-aged women.

Muscle health in Hispanic women. REDLINC VIII.

Objectives: This study aimed to evaluate muscle strength and related factors in Hispanic women.Methods: We studied 593 women between 40 and 89 years old. The women were asked about personal and clinical information. The following instruments were applied: dynamometer (strength), Short Physical Performance Battery (physical performance), SARC-F (sarcopenia), International Physical Activity Questionnaire (physical activity), Menopause Rating Scale (quality of life), 36-item Short Form (general health), and Frailty (Fried's criteria).Results: Low muscle strength rises from 7.1% of women in their 40s to 79.4% in their 80s. Physical performance is low in 0.5% of the first group and rises to 60.5% in the second. The risk of sarcopenia increases significantly from 6.7% in younger women to 58.1% in older women. Frailty, which affects less than 1% of women under age 60 years, increases to 39.5% in their 80s. Sedentary lifestyle rises from 26% to 68.3%. Fragility impairs the quality of life and the perception of health (p < 0.0001). The deterioration of different tests of muscle function is significantly associated with age >70 years (OR 5-20) and with osteoarthritis (OR 4-9). Menopause before the age of 45 years increases the risk of sarcopenia (odds ratio 2.2; 95% confidence interval 1.2-4.0).Conclusion: With aging there is a decrease in muscle strength and an increase in frailty. This entails a decrease in the quality of life.

Association between high levels of gynoid fat and the increase of bone mineral density in women.

Introduction: In women, bone mineral density (BMD) is related to age, estrogenic action, and appendicular skeletal muscle mass (ASMM). The gynoid fat distribution is linked to estrogenic action.Objective: This study aimed to assess whether an increase of gynoid fat is associated with high BMD independent of age and ASMM.Methods: An observational study was performed in women aged between 20 and 79 years. Fat mass, ASMM, and BMD were measured with dual-energy X-ray absorptiometry. The binned scatterplots and multivariate linear regression models were used to study the relationship between hip BMD and age, height, android fat, gynoid fat, and ASMM.Results: Of 673 women invited, 596 accepted to participate. Their mean age was 55.4 ± 12.8 years, weight 63.4 ± 9.4 kg, height 1.61 ± 0.06 m, body mass index 24.54 ± 3.59 kg/m2, average hip BMD 0.914 ± 0.122 g/cm2, android fat 2.12 ± 0.83 kg, gynoid fat 4.54 ± 1.07 kg, and ASMM 15.15 ± 1.97 kg. The final regression model included age (linear coefficient -0.004; 95% confidence interval [CI]: -0.005 to -0.003; p < 0.001), ASMM (linear coefficient 0.013; 95% CI: 0.009 to 0.018; p < 0.001), and gynoid fat (linear coefficient 0.013; 95% CI: 0.005 to 0.022; p < 0.002).Conclusion: Gynoid fat is associated with BMD in the hip independently of age and ASMM.

Postmenopausal androgen-secreting ovarian tumors: challenging differential diagnosis in two cases.

Postmenopausal hyperandrogenism constitutes a very rare condition of tumoral or non-tumoral origin primarily residing either in the ovary or in the adrenal glands. We present herein two cases with this condition; one with abnormal postmenopausal genital bleeding and mild increase in facial hair, and the second with slow-developing hirsutism and virilization. Both cases shared a notorious increase in libido. The laboratory tests showed high levels of testosterone (>100 ng/ml). A normal value of dehydroepiandrosterone sulfate and a normal cortisol level at 9 am after 1 mg of dexamethasone administered at midnight (Nugent test) made an adrenal etiology very unlikely. On the other hand, a high level of inhibine B oriented to an ovarian source. Transvaginal sonography failed to demonstrate an ovarian tumor, but an abdominal and pelvic computed tomography scan or magnetic resonance imaging detected an ovarian tumor and normal adrenal glands. A laparoscopic oophorectomy was performed, and the histological study demonstrated a steroidal cell tumor in the first case and a Leydig cell tumor in the second.

Menopause research in Latin America.

For 15 years, the Collaborative Group for Research of the Climacteric in Latin America (REDLINC) has been conducting research on several topics including age of menopause, metabolic syndrome, quality of life and climacteric symptoms, sexual dysfunction, poor quality of sleep and insomnia, and use of menopausal hormone therapy (MHT) in the general population and among gynecologists. Examples of data to have emerged for this region include the age of menopause (49 years), a high prevalence of metabolic syndrome (42.9%), and a new waist circumference cut-off value for the Latin American population (88 cm). Sexual dysfunction, poor quality of life, and sleep disorders have a prevalence of over 50%, with obesity and sedentary lifestyles affected importantly. MHT use is still low (12.5%), lack of prescription the most important reason for not using it, and gynecologists use MHT for themselves but do not recommend it often to their patients. The prevalence of alternative therapy use, recommended by physicians, is high.

Risk factors of long-term mortality in middle-aged women: a 27-year follow-up cohort.

OBJECTIVE: This study aimed to evaluate the impact of different risk factors on long-term mortality in middle-aged women. METHODS: Women who received preventive health care control between 1990 and 1993 were recruited. Anamnesis and physical examination were recorded. Blood samples for the measurement of glycemia and lipids were taken. Data are reported as of December 2017. RESULTS: We studied 1197 women aged between 40 and 60 years. We observed 183 deaths (survival 84.0%; 95% confidence interval [CI], 81.7-86.1, Kaplan-Meier survival analysis). The main causes of death were cancer (39.9%; 95% CI, 32.7-47.1), cardiovascular disease (22.9%; 95% CI, 16.8-29.1), infectious disease (13.7%; 95% CI, 8.6-18.7), other causes (7.1%, 95% CI, 3.4-10.9), and unspecified cause (6.6%; 95% CI, 2.9-10.2). The final Cox regression model showed the following hazard ratios for mortality: diabetes mellitus 2.51 (95% CI, 1.40-4.51), history of fracture 2.47 (95% CI, 1.15-5.30), history of heart illness 2.06 (95% CI, 1.15-3.72), arterial hypertension 1.51 (95% CI, 1.08-2.11), age 1.07 (95% CI, 1.04-1.10), body mass index 1.06 (95% CI, 1.02-1.09), and sexual intercourse 0.94 (95% CI, 0.89-0.98). Lipid disorders did not reach statistical significance as a risk factor. CONCLUSION: Diabetes, a history of fractures, and cardiovascular risk factors, except lipids, are markers of long-term mortality in middle-aged women. Physicians should pay special attention to these risk factors.

Lack of evidence for the transmission of hepatitis E virus by coagulation factor concentrates based on seroprevalence data.

BACKGROUND: Whether hepatitis E virus (HEV) infection can be transmitted by coagulation factor concentrates remains unclear. OBJECTIVES: The HEV seroprevalence in blood donors and recipients of coagulation factor concentrates was compared to obtain evidence of whether a transmission of HEV by coagulation factor concentrates could occur. METHODS: Archived samples from whole blood donors and patients who had received coagulation factor concentrates were investigated for the presence of anti-HEV IgG by ELISA. Western blotting was used to confirm the positive samples that showed reactivity in the ELISA. RESULTS: Of 357 blood donors, 68 (19%) presented IgG antibodies against HEV. Two of 92 patients who had received coagulation factor concentrates (2·2%) and 1 of the 69 patients who had received plasma-derived products (1·5%) tested positive for anti-HEV IgG. The seroprevalence of HEV in the patient group was significantly lower (P = 0·038) than that in the donor group. The two positive patients were a 72-year-old man treated with plasma-derived products and a 5-year-old girl treated with a recombinant coagulation factor concentrate. CONCLUSION: HEV seroprevalence was significantly higher in the blood donors than in the patients with a history of coagulation factor concentrate administration. In one of two patients with detectable anti-HEV IgG antibodies, the coagulation factor concentrate was not the probable source of infection. Our data suggest that HEV is efficiently inactivated during the manufacturing process of coagulation factor concentrates. Thus, testing for the presence of HEV RNA in plasma donated for the preparation of coagulation factor concentrates may not be necessary.

Establishment of the Ph. Eur. Hepatitis A virus RNA for NAT testing BRP batch 1.

Detection of viral contamination in plasma donations is critical to prevent transmission of infectious diseases. The European Pharmacopoeia (Ph. Eur.) monograph 1646 'Human plasma (pooled and treated for virus inactivation)', requires that plasma pools used for the manufacture of this product be tested, among others, for the presence of hepatitis A virus RNA by nucleic acid testing (NAT) using a positive control containing 100 International Units (IU) of hepatitis A virus (HAV) RNA per mL. To this end, the European Directorate for the Quality of Medicines & HealthCare (EDQM, Council of Europe) organised an international collaborative study under the aegis of the Biological Standardisation Programme, for the establishment of the 1st Biological Reference Preparation (BRP) for HAV RNA for NAT testing. A freeze-dried candidate material was thus prepared and calibrated against the WHO 2nd International Standard for HAV for NAT (00/562) in a study in which thirteen European and North American laboratories including Official Medicines Control Laboratories (OMCLs), manufacturers of plasma-derived products, producers of in vitro diagnostic kits and a blood transfusion centre participated. Based on the outcome of the study, an HAV RNA content of 40 000 IU/vial (corresponding approximately to 4.6 log10 IU/vial) was assigned to the BRP, which was adopted by the Ph. Eur. Commission in March 2016 as Ph. Eur. hepatitis A virus RNA for NAT testing BRP batch 1.

Collaborative study for the establishment of the Ph. Eur. Hepatitis E virus RNA for NAT testing biological reference preparation batch 1.

A new European Pharmacopoeia (Ph. Eur.) biological reference preparation (BRP) had to be established further to the decision to include nucleic acid testing (NAT) for the detection of hepatitis E virus (HEV) RNA in the monograph Human plasma (pooled and treated for virus inactivation) (1646). To this purpose, an international collaborative study was launched in the framework of the Biological Standardisation Programme (BSP) of the European Directorate for the Quality of Medicines & HealthCare (EDQM) and the Commission of the European Union (EU). The study was run in conjunction with the establishment of the 1st World Health Organization (WHO) international reference panel (IRP) for hepatitis E virus RNA genotypes (8578/13). Twenty-three laboratories used in-house developed and commercially available assays to calibrate a lyophilised candidate BRP prepared from a HEV 3f strain positive human plasma against the 1st WHO International Standard (IS) for HEV RNA (6329/10). Results from quantitative and qualitative assays were in good agreement and were combined to calculate an assigned potency. Real-time stability studies indicated that the candidate BRP is very stable at lower temperatures and is thus suitable for long-term use. Based on these results, in February 2016, the Ph. Eur. Commission adopted the candidate material as the hepatitis E virus RNA for NAT testing BRP batch 1, with an assigned unitage of 2.1 × 104 IU/vial (4.32 log10 IU/vial).

Does the menopausal status of female gynecologists affect their prescription of menopausal hormone therapy?

OBJECTIVE: To evaluate whether menopausal status and symptoms among female gynecologists would influence their clinical behavior related to menopausal hormone therapy (MHT). METHODS: Female gynecologists of 11 Latin American countries were requested to fill out the Menopause Rating Scale and a questionnaire containing personal information and that related to MHT use. RESULTS: A total of 818 gynecologists accepted to participate (86.4%). Overall, the mean age was 45.0 ± 10.7 years, 32.2% were postmenopausal, and 17.6% worked in an academic position; 81.8% reported that they would use MHT if they have symptoms, regardless of menopausal status. Academic gynecologists favor personal MHT use at a higher rate (p = 0.04) and have a higher MHT prescription rate as compared to non-academic ones (p = 0.0001). The same trend was observed among post- as compared to premenopausal ones (p = 0.01) and among those who had hysterectomy alone as compared to those experiencing natural menopause (p = 0.002). The presence of menopausal symptoms did not influence their MHT prescription. Current use of MHT and alternative therapy was higher among post- than premenopausal gynecologists (both, p = 0.0001) and among those who had undergone hysterectomy than those experiencing natural menopause. A 38.5% perceived breast cancer as the main risk related to MHT, and a high proportion prescribed non-hormonal drugs (86.4%) or alternative therapies (84.5%). CONCLUSION: Most female gynecologists in this survey would use MHT if menopausal symptoms were present. Postmenopausal physicians use MHT and prescribe it to their symptomatic patients at a higher rate than premenopausal physicians.

[Specific aspects for virus safety of raw materials for cellular-based medicinal products]. / Spezifische Aspekte zur Virussicherheit von Produktionshilfsstoffen für somatische Zelltherapie-Arzneimittel.

Virus safety of cell-based medicinal products is a particular challenge. These products are frequently manufactured using various human- or animal-derived starting and raw materials (serum and feeder-cells) in cell culture, which are possible sources for viral contamination. For living or proliferating cells, no methods for virus inactivation (such as heat or chemical treatment) can be used and the options for testing these medicinal products for all possible viral contaminations are very limited. As a consequence, other safety measures, in particular careful selection and testing of starting and raw materials, are very important. For raw materials, attention should be paid to cell-culture additives of biological origin, such as human and bovine serum and porcine trypsin. Whenever possible, manufacturing steps for inactivation and removal of viruses should be introduced as an additional safety measure. In addition, recombinant products from animal cell cultures (such as growth factors, monoclonal antibodies for cell sorting, viral vectors) are used and have to be tested for virus safety.

Unusual serological response to hepatitis E virus in plasma donors consistent with re-infection.

Hepatitis E virus (HEV)-positive plasma donations, identified by a plasma mini-pool screening approach, were analysed using serological methods for the presence of anti-HEV IgM and IgG. Avidity testing was performed on the IgG-reactive donations. Anti-HEV IgG with high avidity was observed in two donors together with high viral loads, but with the absence of anti-HEV IgM. These data are suggestive of re-infection in a small proportion of plasma donors, which has not previously been reported.

[Viral safety of biological medicinal products]. / Virussicherheit von biologischen Arzneimitteln.

Viral safety of blood donations, plasma products, viral vaccines and gene therapy medicinal products, biotechnical-derived products and tissue and cell therapy products is a particular challenge. These products are manufactured using a variety of human or animal-derived starting materials and reagents; therefore, extensive testing of donors and of cell banks established for production is required. Furthermore, the viral safety of reagents, such as bovine sera, porcine trypsin and human transferrin or albumin needs to be considered. Whenever possible, manufacturing steps for inactivation or removal of viruses should be introduced; however, sometimes it is not possible to introduce such steps for tissues or cell-based medicinal products as the activity and viability of cells will be compromised. It might be possible to implement steps for inactivation or removal of potential contaminating enveloped viruses only for production of small and stable non-enveloped viral gene vectors.