Advances in the Management of Menopausal Symptoms, Fertility Preservation, and Bone Health for Women With Breast Cancer on Endocrine Therapy.

In patients with hormone receptor-positive early-stage breast cancer, adjuvant endocrine treatment administered for up to 5-10 years after diagnosis significantly reduces the risk of recurrence and death. However, this benefit comes with the cost of short- and long-term side effects that may negatively affect patients' quality of life (QoL) and treatment adherence. Among them, the prolonged estrogen suppression associated with the use of adjuvant endocrine therapy in both premenopausal and postmenopausal women can induce life-altering menopausal symptoms, including sexual dysfunction. Moreover, a decrease in bone mineral density and an increased risk of fractures should be carefully considered and prevented whenever indicated. For young women diagnosed with hormone receptor-positive breast cancer with unfulfilled childbearing plans, several challenges should be addressed to manage their fertility and pregnancy-related concerns. Proper counseling and proactive management of these issues are critical components of survivorship and should be pursued from diagnosis through the breast cancer care continuum. This study aims to provide an updated overview of the available approaches for improving the QoL of patients with breast cancer receiving estrogen deprivation therapy, focusing on advances in the management of menopausal symptoms, including sexual dysfunction, fertility preservation, and bone health.

Soy isoflavones decrease fibroglandular breast tissue measured by magnetic resonance imaging in premenopausal women: A 2-year randomized double-blind placebo controlled clinical trial.

BACKGROUND & AIMS: Populations consuming soy have reduced risk for breast cancer, but the mechanisms are unclear. We tested the hypothesis that soy isoflavones, which have ovarian hormone-like effects, can reduce fibroglandular breast tissue (FGBT, 'breast density'), a strong risk marker for breast cancer. METHODS: Premenopausal women (age 30-42 years) were randomized to consume isoflavones (136.6 mg as aglycone equivalents, n = 99) or placebo (n = 98) for 5 days per week up to 2 years, and changes in breast composition measured by magnetic resonance imaging at baseline and yearly intervals were compared after square root transformation using linear mixed effects regression models. RESULTS: By intention-to-treat analyses (n = 194), regression coefficients (ß estimates) of the interaction of time and isoflavone treatment were -0.238 (P = 0.06) and -0.258 (P < 0.05) before and after BMI adjustment, respectively for FGBT, 0.620 (P < 0.05) and 0.248 (P = 0.160), respectively for fatty breast tissue (FBT), and -0.155 (P < 0.05) and -0.107 (P < 0.05), respectively for FGBT as percent of total breast (FGBT%). ß Estimates for interaction of treatment with serum calcium were -2.705 for FBT, and 0.588 for FGBT% (P < 0.05, before but not after BMI adjustment). BMI (not transformed) was related to the interaction of treatment with time (ß = 0.298) or with calcium (ß = -1.248) (P < 0.05). Urinary excretion of isoflavones in adherent subjects (n = 135) significantly predicted these changes in breast composition. Based on the modeling results, after an average of 1.2, 2.2 and 3.3 years of supplementation, a mean decrease of FGBT by 5.3, 12.1, and 19.3 cc, respectively, and a mean decrease of FGBT% by 1.37, 2.43, and 3.50%, respectively, were estimated for isoflavone exposure compared to placebo treatment. Subjects with maximum isoflavone excretion were estimated to have 38 cc less FGBT (or ∼3.13% less FGBT%) than subjects without isoflavone excretion. Decrease in FGBT and FGBT% was more precise with daidzein than genistein. CONCLUSIONS: Soy isoflavones can induce a time- and concentration-dependent decrease in FGBT, a biomarker for breast cancer risk, in premenopausal women, and moderate effects of calcium on BMI and breast fat, suggesting a beneficial effect of soy consumption. TRIAL REGISTRATION: www. CLINICALTRIALS: gov identifier: NCT00204490. TRIAL REGISTRATION: www. CLINICALTRIALS: gov identifier: NCT00204490.

Efficacy of minodronic acid for the prevention of osteoporosis in premenopausal women with gynaecologic disease who undergo bilateral oophorectomy: a single-centre, non-randomised controlled, experimental study.

We evaluated the efficacy of minodronic acid for osteoporosis prevention after bilateral oophorectomy for gynaecologic disease in premenopausal women. Bone mineral density (BMD) and young adult mean (YAM) data from the lumbar vertebrae and femur and bone alkaline phosphatase (BAP)/tartrate-resistant acid phosphatase 5 b (TRACP 5 b) data were obtained for 101 patients. The primary endpoint was the efficacy of minodronic acid for osteoporosis prevention. Fifty-five and 31 patients were assigned to medication and no medication groups, respectively. The decrease in BMD and YAM and the increase in BAP/TRACP-5b were significantly more suppressed in the medication group. There were no significant between-group differences in age at oophorectomy, cancer type, body mass index (BMI), and adjuvant therapy. There were no adverse events due to minodronic acid. Minodronic acid may prevent osteoporosis after oophorectomy in premenopausal women with gynaecologic disease, independent of age at oophorectomy, cancer type, BMI, or adjuvant therapy. Impact statementWhat is already known on this subject? Although the current strategy for osteoporosis prevention after premenopausal bilateral oophorectomy (b-OVX) is hormone therapy (HT), there is no consensus on the treatment duration or adverse events.What do the results of this study add? Therefore, we planned a prospective study to evaluate the efficacy of prophylactic treatment for osteoporosis after b-OVX in premenopausal women with gynaecologic disease using minodronic acid, an oral bisphosphonate, which have a strong evidence of the treatment for osteoporosis. The result showed minodronic acid significantly suppressed the decrease in bone mineral density (BMD) and young adult mean (YAM) and the increase in bone alkaline phosphatase (BAP)/tartrate-resistant acid phosphatase 5b (TRACP 5b). Minodronic acid may prevent osteoporosis after oophorectomy in premenopausal women with gynaecologic disease, independent of age at oophorectomy, cancer type, BMI, or adjuvant therapy.What are the implications of these findings for clinical practice and/or further research? Minodronic acid treatment for osteoporosis prevention after premenopausal b-OVX may be effective as a therapeutic agent after the cessation of HT, or alternative for patients who are contraindicated for HT in breast cancer and thrombosis and should be administered with caution with a history of uterine or ovarian cancer.

Maintenance Laser Treatment for Vaginal Looseness and Sexual Dysfunction: A Double-blinded Randomized Controlled Trial.

BACKGROUND: Vaginal looseness and decreased sensation during intercourse is prevalent in up to 30%-55% of premenopausal women. The efficacy and safety of CO2 laser have been demonstrated for these indications; however, the effect is temporary, up to 6-12 months. No studies regarding the efficacy and safety of adjuvant laser treatments have been conducted to date. AIM: To evaluate the efficacy and safety of a single maintenance CO2 laser treatment in women with vaginal looseness and a concurrent decline in sexual sensation during intercourse. METHODS: This prospective double-blinded randomized controlled trial included premenopausal women who experienced significant temporary improvement in symptoms following previous treatment with CO2 laser due to the abovementioned indications. Participants were randomized to either a single CO2 laser treatment or a single sham treatment. OUTCOMES: Treatment efficacy evaluated with the female sexual function index (FSFI) and the vaginal health index (VHI). RESULTS: Overall, 119 women were included in the study. Mean VHI and FSFI scores were significantly higher in the study group compared to the control group at three months post-treatment (17.34±1.39 vs 12.86±2.23, P = .023 and 30.93±1.79 vs 25.78±1.87, P = .044, respectively). In the study group, both VHI and FSFI returned to baseline at six months post-treatment. The median rate of sexual intercourse per month was increased in the study group at three months post-treatment (8 vs 4, P = .011), and returned to baseline at six months post-treatment. CLINICAL IMPLICATIONS: Maintenance laser treatment provides a temporary non-surgical alternative for women with vaginal looseness and associated sexual dysfunction, though treatment effect seems to be limited to less than 6 months, requiring additional maintenance sessions. STRENGTHS AND LIMITATIONS: The strengths of the current study include a randomized-sham controlled design. Furthermore, VHI was used as an objective evaluation tool, in addition to the FSFI, and assessment of the rate of sexual intercourse. The homogeneity and the relatively small sample size of the cohort is a limitation, and calls for caution in interpretation of the results, and the use of CO2 laser treatment in different age groups and populations. CONCLUSION: A single maintenance laser treatment in women who previously underwent successful treatment with laser is an effective, well-tolerated, and safe procedure for treating symptoms of vaginal looseness and sexual dysfunction, though effects are temporary. Lauterbach R, Aharoni S, Farago N, et al. Maintenance Laser Treatment for Vaginal Looseness and Sexual Dysfunction: A Double-blinded Randomized Controlled Trial. J Sex Med 2022;19:1404-1411.

Female sexual dysfunctions: an overview on the available therapeutic interventions.

INTRODUCTION: There are different types of female sexual dysfunctions (FSDs), and FSD in general has a high prevalence worldwide. Studies of FSD should consider it as a multifactorial disorder that has biological, psychological, environmental, and relational aspects. In this review we discuss the available therapeutic interventions for FSD. EVIDENCE ACQUISITION: For the current narrative review the PubMed database was searched to identify all publications up to 30 March 2021 that were systematic reviews and meta-analyses which examined therapeutic interventions for FSDs based on the diagnostic classifications of ICD-10 and ICD-11. EVIDENCE SYNTHESIS: Thirty systematic reviews and meta-analyses were included in this review. Hormone therapy (HT) and testosterone are effective to improve sexual desire in menopausal women. In these women HT and ospemiphene may improve pain during intercourse. Flibanserin may improve sexual desire and may reduce desire-related distress in premenopausal women. Bremelanotide is effective to improve desire, arousal, and orgasm scores. Evidence are still limited on the efficacy of psychoactive drugs, phosphodiesterase type 5 (PDE5), oxytocin, herbal drugs, and tibolone to treat FSDs. Psychological interventions such as cognitive-behavior therapy, mindfulness training, sensate focus, bibliotherapy are effective for the management of several different FSDs. CONCLUSIONS: The management of FSDs may require multidisciplinary and interdisciplinary approaches. Pharmacological and nonpharmacological interventions appears to have potential as a treatment for FSDs, but there are currently no gold standards regarding recommended treatment modalities, and the duration, frequency, and intensity of therapy sessions.

Vitamin D and green tea extracts for the treatment of uterine fibroids in late reproductive life: a pilot, prospective, daily-diary based study.

OBJECTIVE: The beneficial effects of Vitamin D (VD) and Epigallocatechin gallate (EGCG), a polyphenol of green tea, on the growth of uterine fibroids (UF) were previously described in vitro and in vivo. We have decided to investigate their simultaneous administration in women with UFs in late reproductive life. METHODS: >40 years old n = 16 premenopausal women with intramural (IM) or subserosal (SS) UF of ≥3 cm or several UFs of different sizes, even smaller but with a total diameter ≥3 cm but <10 cm, without further concomitant organic causes of abnormal uterine bleeding, treated with EGCG 300 mg, Vitamin B6 10 mg and VD 50 µg/day for 90 days. Women completed a diary on a daily basis to obtain information about bleeding and pelvic pain. RESULTS: We have observed a significant reduction in UF's mean size both at patient's (-17.8%, p = .03) and at single UF's level (-37.3%, p = .015). The effect was more evident in women with predominant IM (p = .016) in comparison to SS UFs. No significant changes were observed for uterine and ovarian volume and endometrial thickness during treatment. We reported a significant decrease in menstrual flow length of 0.9 day (p = .04) with no modification in cycle length, menstrual flow intensity and menstrual pain intensity. The satisfaction with treatment was in general very high, with no adverse effects reported. CONCLUSION: The concomitant administration of VD and EGCG represents a promising treatment of UF in women of late reproductive life for which hormonal manipulation is not foreseen.

Factors Associated with Serum Vitamin D Metabolites and Vitamin D Metabolite Ratios in Premenopausal Women.

The most representative indicator of vitamin D status in clinical practice is 25(OH)D3, but new biomarkers could improve the assessment of vitamin D status and metabolism. The objective of this study is to investigate the association of serum vitamin D metabolites and vitamin D metabolite ratios (VMRs) with potentially influential factors in premenopausal women. This is a cross-sectional study based on 1422 women, aged 39-50, recruited from a Madrid Medical Diagnostic Center. Participants answered an epidemiological and a food frequency questionnaire. Serum vitamin D metabolites were determined using an SPE-LC-MS/MS platform. The association between participant's characteristics, vitamin D metabolites, and VMRs was quantified by multiple linear regression models. Mean 25(OH)D3 concentration was 49.2 + 18.9 nmol/L, with greater deficits among obese, nulliparous, dark-skinned women, and with less sun exposure. A lower R2 ratio (1,25(OH)2D3/25(OH)D3) and a higher R4 (24,25(OH)2D3/1,25(OH)2D3) were observed in nulliparous women, with high sun exposure, and those with low caloric intake or high consumption of calcium, vitamin D supplements, or alcohol. Nulliparous women had lower R1 (25(OH)D3/Vit D3) and R3 (24,25(OH)2D3/25(OH)D3), and older women showed lower R3 and R4. Vitamin D status modified the association of the VMRs with seasons. VMRs can be complementary indicators of vitamin D status and its endogenous metabolism, and reveal the influence of certain individual characteristics on the expression of hydroxylase enzymes.

Coffee, Tea, and Mammographic Breast Density in Premenopausal Women.

Studies have investigated the associations of coffee and tea with mammographic breast density (MBD) in premenopausal women with inconsistent results. We analyzed data from 375 premenopausal women who attended a screening mammogram at Washington University School of Medicine, St. Louis, MO in 2016, and stratified the analyses by race (non-Hispanic White (NHW) vs. Black/African American). Participants self-reported the number of servings of coffee, caffeinated tea, and decaffeinated tea they consumed. Volpara software was used to determine volumetric percent density (VPD), dense volume (DV), and non-dense volume (NDV). We used generalized linear regression models to quantify the associations of coffee and tea intake with MBD measures. Coffee: ≥1 time/day (ß = 1.06; 95% CI = 0.93-1.21; p-trend = 0.61) and caffeinated tea: ≥1 time/day (ß = 1.01; 95% CI = 0.88-1.17; p-trend = 0.61) were not associated with VPD. Decaffeinated tea (≥1 time/week) was positively associated with VPD in NHW women (ß = 1.22; 95% CI = 1.06-1.39) but not in African American women (ß = 0.93; 95% CI = 0.73-1.17; p-interaction = 0.02). Coffee (≥1 time/day) was positively associated with DV in African American women (ß = 1.52; 95% CI = 1.11-2.07) but not in NHW women (ß = 1.10; 95% CI = 0.95-1.29; p-interaction = 0.02). Our findings do not support associations of coffee and caffeinated tea intake with VPD in premenopausal women. Positive associations of decaffeinated tea with VPD, with suggestions of effect modification by race, require confirmation in larger studies with diverse study populations.

Eficacia y seguridad de ribociclib en combinación con un inhibidor de la aromatasa y un agonista de lhrh en pacientes premenopáusicas con cáncer de mama metastásico, rh positivo, her2 negativo, sin crisis visceral, y sin tratamiento sistémico previo para la enfermedad metastásica / Efficacy and safety of ribociclib in combination with an aromatase inhibitor and an lhrh agonist in premenopausal patients with rh-positive, her2-negative, metastatic breast cancer without visceral crisis, and without prior systemic treatment for metastatic disease

INTRODUCCIÓN: El presente dictamen preliminar expone la evaluación de la eficacia y seguridad de ribociclib en combinación con un IA y un agonista de LHRH en pacientes premenopáusicas con CMM, RH positivo, HER2 negativo, sin crisis visceral, y sin tratamiento sistémico previo para la enfermedad metastásica. El cáncer de mama es la primera causa de muerte por neoplasia maligna en mujeres en el mundo. En el 2019, en Perú se detectaron 4,743 casos nuevos de cáncer de mama en mujeres; y se registraron 1,840 muertes debido a esta neoplasia. Específicamente, el cáncer de mama metastásico (CMM) es una condición incurable. Se estima que la mediana de sobrevida global (SG) en pacientes con CMM es de aproximadamente tres años y que la tasa de SG hasta los 5 años es de aproximadamente 27 %. En ausencia de una enfermedad rápidamente progresiva o una crisis visceral, la terapia endocrina (TE) con supresión ovárica se considera el tratamiento de primera línea para las mujeres premenopáusicas, con CMM, receptor hormonal (RH) positivo, receptor 2 del factor de crecimiento epidérmico humano (HER2) negativo. Las opciones de TE comúnmente utilizadas incluyen moduladores selectivos del receptor de estrógeno (p. ej., tamoxifeno) e inhibidores de aromatasa (IA) no esteroideos (p. ej. anastrozol) o esteroideos (p. ej. exemestano). En EsSalud, este grupo de pacientes es tratado con TE (tamoxifeno, anastrazol, exemestano) más supresión ovárica. Sin embargo, el IETSI recibió una solicitud de evaluación de ribociclib en combinación con TE con IA más supresión ovárica, argumentándose la necesidad de evaluar terapias alternativas que proporcionen mejoras en la SG y calidad de vida de estos pacientes, y que a su vez tengan perfiles de seguridad favorables. METODOLOGÍA: Se realizó una búsqueda sistemática de literatura con el objetivo de identificar evidencia sobre la eficacia y seguridad de ribociclib en combinación con un IA y un agonista de LHRH en pacientes premenopáusicas con CMM, RH positivo, HER2 negativo, sin crisis visceral, y sin tratamiento sistémico previo para la enfermedad metastásica. Se utilizaron las bases de datos PubMed, Cochrane Library y LILACS. Asimismo, se realizó una búsqueda dentro de bases de datos pertenecientes a grupos que realizan evaluaciones de tecnologías sanitarias (ETS) y guías de práctica clínica (GPC), como el Scottish Medicines Consortium (SMC), el National Institute for Health and Care Excellence (NICE), la Canadian Agency for Drugs and Technologies in Health (CADTH), la Haute Autorité de Santé (HAS), el Institute for Quality and Efficiency in Health Care (IQWiG), el Instituto de Evaluación Tecnológica en Salud de Colombia (IETS), la Comissão Nacional de Incorporação de Tecnologias no Sistema Único de Saúde (CONITEC), entre otros; además de la Base Regional de Informes de Evaluación de Tecnologías en Salud de las Américas (BRISA) y páginas web de sociedades especializadas en el manejo del cáncer de mama como National Comprehensive Cancer Network (NCCN), European Society for Medical Oncology (ESMO) y American Society of Clinical Oncology (ASCO). Se hizo una búsqueda adicional en la página web del registro de ensayos clínicos administrado por la Biblioteca Nacional de Medicina de los Estados Unidos (https://clinicaltrials.gov/) e International Clinical Trial Registry Platform (ICTRP) (https://apps.who.int/trialsearch/), para poder identificar ensayos clínicos en curso o cuyos resultados no hayan sido publicados para, de este modo, disminuir el riesgo de sesgo de publicación. RESULTADOS: se describe la evidencia disponible según el orden jerárquico del nivel de evidencia o pirámide de Haynes 6S3, siguiendo lo indicado en los criterios de elegibilidad. CONCLUSIONES: El objetivo del presente dictamen preliminar fue evaluar la mejor evidencia científica sobre la eficacia y seguridad de ribociclib en combinación con un IA y un agonista de LHRH en pacientes premenopáusicas con CMM, RH positivo, HER2 negativo, sin crisis visceral, y sin tratamiento sistémico previo para la enfermedad metastásica (primera línea de tratamiento para la enfermedad metastásica). El comparador de interés fue la TE con tamoxifeno o un IA (anastrazol, exemestano) más la supresión ovárica. Se incluyeron tres GPC elaboradas por la ESMO, la NCCN y la ASCO; tres ETS realizadas por la CADTH de Canadá, el IQWiG de Alemania y la CONETEC de Argentina; y tres publicaciones del estudio MONALEESA-7 (Tripathy et al. 2018; Im et al. 2019; Harbeck et al. 2020). Las tres GPC identificadas recomendaron el uso de un inhibidor de CDK 4/6, como ribociclib, combinado con un IA más supresión ovárica con un agonista de LHRH, en la población de interés. La NCCN y la ESMO también recomendaron el uso de TE (IA o tamoxifeno) más supresión ovárica en esta población. La evidencia utilizada para respaldar la recomendación fue el estudio MONALEESA-7. En cuanto a las recomendaciones de las ETS internacionales, el IQWiG y la CONETEC realizaron recomendaciones desfavorables para ribociclib, mientras que la CADTH elaboró una recomendación a favor del uso de ribociclib. Las recomendaciones se basaron en los resultados del estudio MONALEESA-7. En líneas generales, los resultados de MONALEESA-7 (ECA de fase 3, doble ciego) sugieren una mayor SG y SLP con ribociclib respecto al placebo en la población objetivo del presente dictamen. Además, el ribociclib se asoció con una mayor tasa de EA serios y severos, y una calidad de vida similar en relación con el placebo. Sobre la calidad de la evidencia, MONALESSA-7 presenta limitaciones metodológicas que amenazan la validez de los resultados reportados. En primer lugar, los resultados de eficacia se basaron en análisis de desenlaces basados en imágenes radiográficas, como la SLP (que no es una medida directa de beneficio clínico), y análisis interinos con datos prematuros de SG. Además, los análisis de calidad de vida presentaron una importante pérdida de información. Así se evidencia un alto grado de incertidumbre en relación al beneficio clínico de ribociclib. A ello se le suma la tasa significativa de EA severos y serios reportados con ribociclib en el corto plazo, y la incertidumbre sobre la certeza de los resultados de calidad de vida. Ribociclib es un medicamento que, de aprobarse, tendría un impacto presupuestario importante en el contexto de EsSalud, por lo que su alto costo tendría que traducirse en un claro beneficio clínico, el cual pueda justificar que se deje de invertir en tecnologías efectivas y menos costosas para los asegurados para que, en su lugar, se financie ribociclib. La población objetivo del presente dictamen tiene una alternativa de tratamiento disponible en EsSalud, que es la TE (tamoxifeno o un IA) con supresión ovárica, opción de tratamiento que sigue siendo recomendada en las GPC internacionales, y tiene una amplia experiencia de uso en la institución. Por todo lo expuesto, el IETSI no aprueba el uso de ribociclib en combinación con un IA y un agonista de LHRH en pacientes premenopáusicas con CMM, RH positivo, HER2 negativo, sin crisis visceral, y sin tratamiento sistémico previo para la enfermedad metastásica.

Effect of the Intake of Isoflavones on Risk Factors of Breast Cancer-A Systematic Review of Randomized Controlled Intervention Studies.

Epidemiological studies suggest that high intake of soy isoflavones may protect against breast cancer, but causal relationships can only be established by experimental trials. Thus, we aimed to provide a systematic review of randomized controlled trials (RCTs) on the effect of an isoflavone intake on risk factors of breast cancer in healthy subjects. After a systematic literature search in PubMed, 18 different RCTs with pre- and/or postmenopausal women were included and investigated for details according to the PRISMA guideline. In these studies, isoflavones were provided by soy food or supplements in amounts between 36.5-235 mg/d for a period of 1-36 months. Breast density, estrogens including precursors, metabolites, estrogen response such as length of menstrual cycle, and markers of proliferation and inflammation were considered. However, in most studies, differences were not detectable between isoflavone and control/placebo treatment despite a good adherence to isoflavone treatment, irrespective of the kind of intervention, the dose of isoflavones used, and the duration of isoflavone treatment. However, the lack of significant changes in most studies does not prove the lack of effects as a sample size calculation was often missing. Taking into account the risk of bias and methodological limitations, there is little evidence that isoflavone treatment modulates risk factors of breast cancer in pre- and postmenopausal women. Future studies should calculate the sample size to detect possible effects and consider methodological details to improve the study quality.

Frequency and determinants of vitamin D deficiency among premenopausal and postmenopausal women in Karachi Pakistan.

BACKGROUND: Vitamin D deficiency is becoming a serious public health problem, even in sun-drenched cities like Karachi, Pakistan. We investigated the prevalence of vitamin D deficiency and its association with sociodemographic characteristics, anthropometric measures, and lifestyle factors among premenopausal and postmenopausal women (n = 784). METHODS: Face-to-face interviews were conducted to collect information and serum concentrations of 25-hydroxyvitamin D were measured after the interviews. RESULTS: A total of 57% of women were vitamin D deficient with higher vitamin D deficiency found among premenopausal women (64.7%) compared to postmenopausal women (49%). The median serum concentrations of 25-hydroxyvitamin D (IQR) were 16.7 ng/ml (IQR 9.8-30.0). Factors associated with vitamin D deficiency were lower socioeconomic status (OR 2.00; 95% CI 1.15-3.48), younger age with highest vitamin D deficiency found in < 35 years of age group (OR 3.11; 95% CI 1.76-5.51), and winter season (OR 1.51, 95% CI 1.07-2.15) after adjusting for multiple confounders. The use of vitamin D supplement (OR 0.59, 95% CI 0.38-0.92) and vigorous exercise (OR 0.20, 95% CI 0.05-0.80) were protective against vitamin D deficiency. CONCLUSIONS: The study shows a high prevalence of vitamin D deficiency, with detrimental health effects, among younger women belonging to lower socioeconomic status and during the winter season. The use of vitamin D supplements and vigorous exercise were protective measures. Public health campaigns are needed for education and awareness about vitamin D deficiency to improve vitamin D status for younger women living in poor environments.

Zinc absorption and zinc status are reduced after either sleeve gastrectomy or Roux-en-Y gastric bypass in premenopausal women with severe obesity studied prospectively over 24 postoperative months.

BACKGROUND: Roux-en-Y gastric bypass (RYGBP) is known to reduce zinc absorption; the effects of vertical sleeve gastrectomy (SG) and its long-term implications on zinc absorption have not yet been studied. OBJECTIVE: The aim was to evaluate the effects of SG and RYGBP on zinc absorption and zinc status in premenopausal women with severe obesity up to 24 mo after surgery. METHODS: Twenty-six premenopausal women undergoing SG [BMI (in kg/m2): 37.3 ± 3.2] and 32 undergoing RYGBP (BMI: 42.0 ± 4.2) were studied. A series of anthropometric, dietary, and zinc status parameters (plasma and hair zinc), and the size of the exchangeable zinc pool (EZP), as well as percentage zinc absorption from a standardized dose using a stable isotope methodology were evaluated in the patients before the surgical procedure and at 12 and 24 mo after SG or RYGBP. SG patients received 15 mg and RYGBP received 25 mg of supplemental Zn/d. RESULTS: In premenopausal women, zinc absorption was decreased by 71.9% and 52.0% in SG and RYGBP, respectively, 24 mo postsurgery, compared with initial values. According to 2-factor repeated-measures ANOVA, time effect was significant (P = <0.0001), but not time × group interaction (P = 0.470). Plasma zinc below the cutoff point of 70 µg/dL increased from 0 to 15.4% and 38.1% in SG and RYGBP, respectively. Mean EZP was significantly reduced 24 mo after surgery, although no time × group interactions were observed. Hair zinc did not change across time or between groups. CONCLUSIONS: Both SG and RYGBP have profound effects on zinc absorption capacity, which are not compensated for after 24 mo. Although zinc absorption reduction was similar in both types of surgeries, plasma zinc was more affected in RYGBP than SG, despite greater zinc supplementation in RYGBP.This trial was registered at http://www.isrctn.com as ISRCTN31937503.

Chemoprevention Agents to Reduce Mammographic Breast Density in Premenopausal Women: A Systematic Review of Clinical Trials.

Background: Higher mammographic breast density (MBD) is associated with an increased risk of breast cancer when compared with lower MBD, especially in premenopausal women. However, little is known about the effectiveness of chemoprevention agents in reducing MBD in premenopausal women without a history of breast cancer. Findings from this review should provide insight on how to target MBD in breast cancer prevention in premenopausal women with dense breasts. Methods: We searched 9 electronic databases for clinical trials in English, Spanish, French, or German published until January 2020. Articles evaluating the association of pharmacological agents and MBD were included. Data were extracted on methods, type and dose of intervention, outcomes, side effects, and follow up. Quality of the studies was assessed using the US Preventive Services Task Force criteria. Results: We identified 7 clinical trials evaluating the associations of 6 chemoprevention agents with changes in MBD in premenopausal women without history of breast cancer. The studies evaluated selective estrogen-receptor modulators (n = 1); gonadotropin-releasing hormone agonists (n = 2); isoflavones (n = 1); vitamin D (n = 1); and Boswellia, betaine, and mayo-inositol compound (n = 1). Hormonal interventions were associated with net reductions in percent density (tamoxifen [13.4%], leuprolide acetate [8.9%], and goserelin [2.7%]), whereas nonhormonal (vitamin D and isoflavone) interventions were not. However, MBD returned to preintervention baseline levels after cessation of gonadotropin-releasing hormone agonists. Conclusions: A limited number of chemoprevention agents have been shown to reduce MBD in premenopausal women. Identification of new and well-tolerated chemoprevention agents targeting MBD and larger studies to confirm agents that have been studied in small trials are urgent priorities for primary breast cancer prevention in premenopausal women with dense breasts.

Randomised Controlled Trial of Nutritional Supplement on Bone Turnover Markers in Indian Premenopausal Women.

Young Indian women may be at risk of poor bone health due to malnutrition. The aim of this study was to examine the effects on bone metabolism of a nutritional supplement in women aged 25 to 44. The nutritional supplement was a protein-rich beverage powder fortified with multi-micronutrients including calcium (600 mg), vitamin D (400 IU), and vitamin K (55 mcg) per daily serving, while a placebo supplement was low-protein non-fortified isocaloric beverage powder. This 6-month randomised, controlled trial showed favorable changes in bone turnover markers (decreased) and calcium homeostasis; such changes in older adults have been associated with slowing of bone loss and reduced fracture risk. For example, serum CTX decreased by about 30% and PINP by about 20% as a result of the increase in calcium intake. There were also changes in the ratio of carboxylated to undercarboxylated osteocalcin and such changes have been linked to a slowing of bone loss in older subjects. For example, the ratio increased by about 60% after 3 months as a result in the improvement in vitamin K status. Finally, there were improvements in the status of B vitamins, and such changes have been associated with reductions in homocysteine, but it is uncertain whether this would affect fracture risk. The product was generally well tolerated. This study shows the nutritional supplement holds promise for improved bone health among young Indian women.

Coffee consumption and breast cancer risk: a narrative review in the general population and in different subtypes of breast cancer.

PURPOSE: Most of the existing literature reports no association or a slight negative association between coffee consumption and the risk of developing breast cancer. However, the level of risk differs when considering various subgroups, such as menopausal status, hormonal status of the tumor or genetic mutations. The present review based on a literature search sets the point on the potential influence of a common daily drink, coffee, on the risk of developing breast cancer in the general population, in different subgroups of women and the consequences of drinking coffee after breast cancer has been diagnosed and treated. RESULTS: This review confirms that in the general population, there is no association between coffee intake and breast cancer risk or a slight protective effect, even at high dosages. Coffee is inversely associated with breast cancer risk in postmenopausal women and in women carrying a BRCA1 mutation. Possible risk differences exist between slow and fast caffeine metabolizers and with weight. Coffee consumption after breast cancer diagnosis and surgery, associated with tamoxifen and/or radiotherapy, reduced the occurrence of early events. The effects of coffee intake are less clear in other subgroups, mainly premenopausal women, women carrying a BRCA2 mutation and tumors with variable hormonal status (positive or negative for ER/PR) and would need additional studies.

Effects of acupuncture on anthropometric and serum metabolic parameters in premenopausal overweight and obese women: a randomized, patient- and assessor-blind, sham-controlled clinical trial.

OBJECTIVE: The aim of this study was to examine the effect of acupuncture on obesity-related parameters with regard to metabolomics. METHODS: This two-arm parallel, patient- and assessor-blind, sham-controlled randomized clinical trial included 120 obese participants. Participants were randomized into two groups. The treatment group received a combined intervention of manual acupuncture (MA) plus electroacupuncture (EA), while the control group received a combination of sham acupuncture interventions consisting of sham MA plus sham EA for 6 weeks. The serum lipid levels were measured as the primary outcome measure and anthropometric parameters and serum metabolic profiles including amino acids and carnitines were measured as secondary outcome measures. RESULTS: The serum lipid levels and anthropometric measurements did not significantly differ between groups, while body weight, body mass index (BMI), and waist circumference were improved within each group and the level of high-density lipoprotein cholesterol increased over time in the treatment group. There were no significant differences in amino acid levels between groups, while certain carnitine (C2, C4, C6, and l-carnitine) levels were significantly increased (p < 0.05) in the treatment group compared to the control group. CONCLUSION: In summary, 6 weeks of acupuncture treatment did not affect anthropometric and serum metabolic parameters, with the exception of certain carnitines, when compared to sham acupuncture. The observation of increased carnitine levels in the acupuncture group could result in potential long-term benefits to obese individuals. Additional studies are needed to investigate the long-term effects of acupuncture on lipid metabolism and the underlying mechanism of action. TRIAL REGISTRATION NUMBER: This study is registered at ClinicalTrials.gov (NCT02066090).

Prospective observational study of chemotherapy-induced alopecia after sequential FEC + taxane and the effects of age in breast cancer patients.

BACKGROUND: Chemotherapy-induced alopecia (CIA) is a common and quite distressing adverse effects of chemotherapy. There are few detailed observational studies of CIA or of the impact of age on CIA. We performed a prospective observational study to investigate the prevalence and degree of CIA, including CIA of eyebrows, eyelashes, and body, and we examined patient's recovery from CIA, focusing on age-depending effects. METHODS: We analyzed 68 female Japanese patients with breast cancer (median age 53 years, range 29-76 years) who received perioperative adjuvant chemotherapy with fluorouracil/epirubicin/cyclophosphamide (FEC) and taxane. A questionnaire was administered at the point of chemotherapy completion and 6 and 12 months after chemotherapy completion. RESULTS: CIA occurred in all patients, with severe hair loss irrespective of age. CIA occurred mainly in the scalp but also in the eyebrows, eyelashes, and body for most of the patients. There were significant associations between the patient's age and the onset of hair regrowth in the eyebrows, eyelashes, and body. The onset of eyebrows, eyelash, and body hair growth were significantly shorter in the premenopausal patients. Any hair changes (e.g., thinned diameter, softer texture, curlier structure) were reported by 85.3% of the patients. CONCLUSIONS: Severe CIA occurred in all 68 patients who received FEC and taxane chemotherapy. The present findings provide the first data demonstrating that age was not associated with the degree or incidence of hair loss, but age affected the recovery from CIA. These results contribute more accurate information provision and insights regarding the proper treatment of CIA.

Effects of Korean Red Ginseng (Panax ginseng C.A. Meyer) on Menopausal Symptoms in Premenopausal Women After Gynecologic Cancer Surgery: A Double-Blind, Randomized Controlled Trial.

Objectives: Korean red ginseng (KRG) has been widely used as an alternative medicine to relieve menopausal symptoms. However, there is still a lack of clinical studies showing the effects of KRG on menopausal symptoms after gynecologic cancer surgery. Therefore, the authors investigated the effects of KRG on surgical menopause symptoms in premenopausal women with gynecologic cancer. Design: A double-blind, randomized, placebo-controlled clinical trial was conducted. Settings/Location: The study was performed at Severance Hospital at the Yonsei University College of Medicine in Seoul, Korea. Subjects: Fifty-five premenopausal women diagnosed with gynecologic cancer were enrolled in the study. Interventions: Patients were randomly assigned to a KRG (n = 29) or a placebo control group (n = 26). Subjects were administered either KRG (a total of 3 g per day) or placebo supplements for 12 weeks. Outcome measures: Patients' physical measurements (height, weight, and blood pressure) and blood samples (lipid profiles, hormone profiles, biochemical profiles, and neutrophil-to-lymphocyte ratio) at baseline and at 12 weeks were compared. Changes in menopausal symptoms based on the Menopause Rating Scale (MRS) were also compared between these two time points and two groups. Results: After 12 weeks, the MRS score was significantly reduced in each group (p = 0.001 and p = 0.001, respectively), but there were no significant differences between the two groups (p = 0.661). No adverse events were observed in either group. After comparing 11 MRS symptoms between the two groups, the KRG group seemed to be superior to the placebo group on the subscale of sexual complaints (p < 0.05). Conclusions: Through the study, KRG did not show absolute relief of surgical menopause symptoms in premenopausal women after gynecologic cancer surgery. However, the study did demonstrate that KRG may be effective in reducing sexual complaints. Further studies are required to evaluate the long-term effects of KRG in a larger patient population.

Low Levels of Omega-3 Long-Chain Polyunsaturated Fatty Acids Are Associated with Bone Metastasis Formation in Premenopausal Women with Breast Cancer: A Retrospective Study.

In the present study, we investigated various biochemical, clinical, and histological factors associated with bone metastases in a large cohort of pre- and postmenopausal women with breast cancer. Two hundred and sixty-one consecutive women with breast cancer were included in this study. Breast adipose tissue specimens were collected during surgery. After having established the fatty acid profile of breast adipose tissue by gas chromatography, we determined whether there were differences associated with the occurrence of bone metastases in these patients. Regarding the clinical and histological criteria, a majority of the patients with bone metastases (around 70%) had tumors with a luminal phenotype and 59% of them showed axillary lymph node involvement. Moreover, we found a negative association between the levels of n-3 long-chain polyunsaturated fatty acids (LC-PUFA) in breast adipose tissue and the development of bone metastases in premenopausal women. No significant association was observed in postmenopausal women. In addition to a luminal phenotype and axillary lymph node involvement, low levels of n-3 LC-PUFA in breast adipose tissue may constitute a risk factor that contributes to breast cancer bone metastases formation in premenopausal women.