Benefits of a Multidisciplinary Women's Sexual Health Clinic in the Management of Sexual and Menopausal Symptoms After Pelvic Radiotherapy.

OBJECTIVE: The objective of this study was to examine patterns of care and outcomes of female cancer patients treated for sexual and menopausal symptoms following pelvic radiotherapy (PRT) at our institution's multidisciplinary Sexuality, Intimacy, and Menopause (SIMS) Program. MATERIALS AND METHODS: We performed a retrospective review of 69 female patients who received PRT for gynecologic or gastrointestinal malignancies and were referred for SIMS Program intervention. Indications for referral and treatment patterns were summarized. Preintervention and postintervention, patients were screened at follow-up visits, and symptoms were recorded. Statistics were performed using Stata 13.1. RESULTS: Cancer types included cervical (53.6%), endometrial (31.9%), anorectal (5.8%), and vulvar/vaginal (8.7%). The median age was 48 years (interquartile range: 38 to 58 y). Patients were educated on vaginal lubricants, moisturizers, and dilator therapy both before and after PRT. Reasons for SIMS referral included persistent menopausal symptoms (50.7%), dyspareunia (40.6%), vaginal dryness (37.7%), decreased libido (17.4%), intimacy concerns (17.4%), and/or physical examination alterations (27.5%). SIMS interventions included vaginal estrogen (77.3%), nonhormonal climacteric interventions (53%), systemic hormone therapy (31.8%), dehydroepiandrosterone (4.6%), testosterone cream (4.6%), and/or psychological pharmacotherapy or counseling (13.6%). With a median follow-up of 36 months (interquartile range: 18 to 58 mo), sexual symptoms improved or were stable in 83.6%, while menopausal symptoms improved or were stable in 80.5%. CONCLUSIONS: This study highlights the importance of multidisciplinary care in improving the sexual and menopausal symptoms of women after PRT. Future work examining the impact of intervention timing with respect to PRT and measures of patient satisfaction is warranted.

Bone health and osteoporosis screening in gynecologic cancer survivors.

Cancer treatment-induced bone loss is a known side effect of cancer therapy that increases the risk of osteoporosis and bone fracture. Women with gynecologic cancer are at increased risk of bone loss secondary to the combined effect of oophorectomy and adjuvant therapies. Data regarding bone loss in women with gynecologic cancers are overall lacking compared to other cancer populations. Consequently, guidelines for osteoporosis screening in women with cancer are largely based on data generated among non-gynecologic cancer survivors. This article reviews current available data of bone health in women with gynecologic cancer, summarizes best-available guidelines for screening for osteoporosis in women with cancer, and provides guidance for osteoporosis screening in women with gynecologic cancers based on best available evidence.

Relationship of menopausal symptoms and ovarian reserve in reproductive-aged cancer survivors.

PURPOSE: This study sought to evaluate the prevalence of menopausal symptoms in a population of reproductive-aged women remote from cancer therapy compared with a group of healthy similar-aged controls and with a cohort of late reproductive-aged (LR) controls. METHODS: Participants were assessed for symptoms of menopause, early follicular phase hormones, and ultrasound examinations. Menopausal symptoms were analyzed in exposed participants and controls using χ2 analyses, Wilcoxon-Mann Whitney tests, and multivariable logistic regression models. RESULTS: One hundred seventy cancer survivors, 135 similar-aged controls, and 71 LR controls were followed prospectively for an average of 38 months. Compared with similar-aged controls, a greater proportion of survivors reported vasomotor symptoms at some point over the study period (35% vs 19%, p < 0.01), and this proportion was similar to LR controls (44%, p = 0.22). Survivors were more likely to be bothered by vaginal dryness (27%) than similar-aged controls (16%, p = 0.02) or LR controls (14%, p = 0.02). FSH levels were 38.4% higher in those with vasomotor symptoms compared with those without symptoms (p = 0.021). CONCLUSIONS: Reproductive-aged cancer survivors have a higher prevalence of vasomotor symptoms and vaginal dryness than their similar-aged peers. IMPLICATIONS FOR CANCER SURVIVORS: Providers should be attuned to the high prevalence of menopausal symptoms in cancer survivors.

Microablative fractional CO2 laser for the genitourinary syndrome of menopause: power of 30 or 40 W?

This retrospective case-control study aimed to compare 30 versus 40 W power of CO2 laser for the therapy of genitourinary syndrome of menopause (GSM). Postmenopausal women with severe intensity of dyspareunia and dryness were eligible to be included in this study. Primary outcomes were dyspareunia and dryness. Secondary outcomes were itching/burning, dysuria, frequency and urgency, Female Sexual Function Index (FSFI), vaginal maturation value (VMV), and Vaginal Health Index Score (VHIS). One laser therapy was applied every month for 3 months. Outcomes were evaluated at baseline and 1 month following the 3rd therapy. Fifty (25 per group) women were included in this study. In the 30-W group, mean improvement of dyspareunia, dryness, itching/burning, FSFI, VMV, and VHIS was 6.1 ± 1.7, 6.0 ± 1.9, 5.9 ± 2.0, 16.6 ± 6.7, 29.9 ± 13.0, and 11.0 ± 2.9, respectively (within group comparisons all p < 0.001). In the 40-W group, mean improvement of dyspareunia, dryness, itching/burning, FSFI, VMV, and VHIS was 6.1 ± 1.7, 6.5 ± 2.0, 5.2 ± 2.5, 14.8 ± 7.1, 25.0 ± 13.4, and 10.5 ± 4.1, respectively (within-group comparisons, all p ≤ 0.001). Comparison between 30 and 40 W revealed that mean improvement or presence of all GSM symptoms and clinical signs was not statistically significant different. CO2 laser therapy may improve GSM symptoms and clinical signs. This improvement did not seem to associate to power of 30 or 40 W.

El láser fraccionado de CO2 como tratamiento del síndrome genitourinario de la menopausia: revisión de la evidencia y recomendaciones de uso / The fractional CO2 laser for treatment of genitourinary syndrome of menopause: evidence update and using recommendations

Publicaciones recientes han demostrado que el láser fraccionado de CO2 es una opción terapéutica no hormonal efectiva, sencilla, bien tolerada y sin efectos adversos, para el tratamiento del síndrome genitourinario de la menopausia. Debido a la restauración del epitelio vaginal, el proceso de neocolagénesis y una mayor vascularización, obtenidas por la reacción térmica desencadenada, se restablecerá la estructura de la mucosa, su grosor y trofismo funcional, mejorando por tanto la sintomatología. No obstante, son necesarios estudios a largo plazo, controlados, frente a placebo, estrógenos locales y otros tratamientos no hormonales, para validar la duración de los efectos y la seguridad de las sucesivas aplicaciones. El objetivo de este trabajo es revisar la evidencia disponible hasta la fecha, relacionada con esta terapia emergente y proponer unas recomendaciones de uso (AU)

Recent reported studies have demonstrated that non-invasive fractional CO2 laser is a valid, safe, effective and well tolerated therapeutic option, without adverse events to treat the genitourinary syndrome of menopause. The heat shock effect induces the increase of vaginal epithelium thickness, the new glycogen content and the vascular changes, improving the vaginal epithelium structure, functionality and menopausal symptoms. Nevertheless, duration of treatment effects and safety of repeated session are not clear enough. Further controlled long-term follow-up research on laser versus placebo, local estrogens and other non-hormonal therapies are needed. The aim of this paper is to review the scientific evidence related to this emergent treatment and proposing recommendations of use (AU)

Enhancing Care of the Survivor of Gynecologic Cancer: Managing the Menopause and Radiation Toxicity.

It is expected that there will be 290,000 cases of gynecologic cancers in 2016. Of these cancers, 60,000 will be endometrial and 22,000 will be ovarian-the two most common gynecologic cancers. Endometrial and ovarian cancers occur in menopausal women with mean ages of 60 and 63, respectively. The majority of endometrial cancers are early stage, and 5-year survival is considered good at upwards of 75%. For ovarian cancer, while survival rates have improved, the 5-year survival rate for the most common stage (stage III) is 40%. Thus, a substantial number of patients with gynecologic cancer are menopausal, and a significant number of patients are survivors, particularly of endometrial cancers. It will be important for survivors of gynecologic cancers to receive care tailored to their needs as women and to mitigate gender-specific side effects of their cancer treatment.

Interaction between a single exposure and age in cohort-based hazard rate models impacted the statistical distribution of age at onset.

OBJECTIVE: Statistical interaction between a single, instantaneous exposure and attained age (age during follow-up; attained age = age at exposure + time since exposure) is used in risk analyses to assess potential effect modification by unmeasured factors correlated with age. However, the impact of such interaction on the statistical distribution of age-at-onset of outcome (disease or death) is infrequently assessed. We therefore explored the impact of such interaction on the shape of the onset-age distribution. STUDY DESIGN AND SETTING: We use for illustration age-at-onset of radiation-related early menopause in a cohort of female Japanese Atomic Bomb Survivors. The statistical distribution of age-at-onset was derived from a parametric hazard rate model fit to the data, assuming an underlying Gaussian onset-age distribution among nonexposed women. RESULTS: Commonly used forms of exposure-by-age (attained age) interaction led to unnatural estimates of the age-specific rate function and unreasonable estimates of the onset-age distribution among exposed women, including positive risk of menopause before menarche. CONCLUSION: We recommend that researchers examine the distribution of age-at-onset and exposure-age interaction when conducting risk analyses. To distinguish this from potential etiologic interaction between exposure and unmeasured factors represented by age as a surrogate, richer models or additional data may be required.

[Age of menopause in patients with differentiated thyroid cancer treated with radioiodine]. / Edad de menopausia en pacientes tratadas con I131 por cáncer diferenciado de tiroides.

INTRODUCTION: Differentiated thyroid cancer (DTC) is an increasingly frequent endocrinological disease. Radioiodine is a key component of treatment. OBJECTIVE: To analyze the effects of I(131) therapy on ovarian and reproductive function. MATERIAL AND METHODS: We retrospectively analyzed data from 202 women treated with radioiodine for DTC in our service from 1985-2008. Data on age at menopause in patients and their mothers and sisters, menstrual history, fertility and neonatal abnormalities were collected. RESULTS: Menopause occurred in 34 patients at follow-up. The mean age at menopause in patients was 49.94+/-3.45 while that in their mothers and sisters was 49.20+/-5.37 and 48.73+/-3.74 years, respectively. Three patients had transient amenorrhea. No infertility or neonatal alterations were found. CONCLUSIONS: In our series, menopause did not occur earlier in patients than in their first degree relatives. No significant alterations in neonatal health, fertility or menstruation were found.

Edad de menopausia en pacientes tratadas con I131 por cáncer diferenciado de tiroides / Age of menopause in patients with differentiated thyroid cancer treated with radioiodine

Introducción El cáncer diferenciado de tiroides es la neoplasia endocrina mas frecuente. El tratamiento con radioyodo es una pieza importante del tratamiento. Objetivo Analizar los efectos de esta terapia sobre la función ovárica y reproductiva en las pacientes tratadas con I131.Material y método Se realizó un análisis retrospectivo de los datos de 202 mujeres afectas de cáncer diferenciado de tiroides y tratadas con I131 en nuestro servicio entre 1985–2008. Se recogieron datos acerca de la edad de la menopausia de las pacientes y de sus madres y hermanas, historia menstrual, fertilidad y patología neonatal.Resultados34 mujeres alcanzaron la edad de menopausia durante su seguimiento, con una edad media de 49,94±3,45 años mientras que en madres y hermanas fue de 49,20±5,37 y 48,73±3,74 años, respectivamente. Tres de estas pacientes presentaron oligoamenorrea transitoria. Ninguna tuvo infertilidad ni alteraciones en la descendencia. Conclusiones En nuestra serie no se halló un adelanto significativo de la edad de la menopausia respecto a sus familiares de primer grado ni una incidencia significativa de patología neonatal, infertilidad y/o alteraciones menstruales (AU)

Introduction Differentiated thyroid cancer (DTC) is an increasingly frequent endocrinological disease. Radioiodine is a key component of treatment. Objective To analyze the effects of I131 therapy on ovarian and reproductive function. Material and methods We retrospectively analyzed data from 202 women treated with radioiodine for DTC in our service from 1985–2008. Data on age at menopause in patients and their mothers and sisters, menstrual history, fertility and neonatal abnormalities were collected. Results Menopause occurred in 34 patients at follow-up. The mean age at menopause in patients was 49.94±3.45 while that in their mothers and sisters was 49.20±5.37 and 48.73±3.74 years, respectively. Three patients had transient amenorrhea. No infertility or neonatal alterations were found. ConclusionsIn our series, menopause did not occur earlier in patients than in their first degree relatives. No significant alterations in neonatal health, fertility or menstruation were found (AU)

Ovarian ablation or suppression in premenopausal early breast cancer: results from the international adjuvant breast cancer ovarian ablation or suppression randomized trial.

BACKGROUND: Substantial survival benefits exist for patients with early-stage breast cancer who undergo treatment with single-modality tamoxifen, ovarian ablation or suppression, or chemotherapy. To determine whether additional benefits exist with combined treatment, the Adjuvant Breast Cancer (ABC) Trials were undertaken. METHODS: The ABC Ovarian Ablation or Suppression Trial randomly assigned pre- and perimenopausal patients with early-stage breast cancer who were receiving prolonged (5 years) tamoxifen treatment with or without chemotherapy to ovarian ablation or suppression (by oophorectomy, ovarian irradiation, or treatment with luteinizing hormone-releasing hormone agonist) versus no ovarian ablation or suppression. Trial endpoints included relapse-free and overall survival. Hazard ratios (HRs) were derived from Cox models, and all statistical tests were two-sided. RESULTS: Between 1993 and 2000, 2144 (1063 ovarian ablation or suppression, 1081 no ovarian ablation or suppression) patients were randomly assigned. A total of 942 (89%) received ovarian ablation or suppression as allocated. Overall, no evidence of a benefit for ovarian ablation or suppression was observed for relapse-free survival (relapse in the ovarian ablation/suppression versus no ovarian ablation/suppression group, 290 events versus 306 events, HR = 0.95, 95% confidence interval [CI] = 0.81 to 1.12; P = .56) or overall survival (death from any cause in the ovarian ablation or suppression versus no ovarian ablation/suppression group, 215 events versus 230 events, HR = 0.94, 95% CI = 0.78 to 1.13; P = .44), nor were differences seen after adjustment for age, nodal status, or estrogen receptor (ER) status. CONCLUSION: Overall, no added effect of ovarian ablation or suppression was seen on relapse-free survival or overall survival of premenopausal women who were treated for early-stage breast cancer. However, the role of ovarian ablation or suppression in young (<40 years) women with ER-positive tumors, especially those not receiving chemotherapy, requires further study.

The fertility- and menopause-related information needs of younger women with a diagnosis of breast cancer: a qualitative study.

The use of chemotherapy and endocrine therapies in the treatment of pre-menopausal women carries with it reproductive and gynaecological implications which younger women may find both unpleasant and discordant with plans for childbearing. This study aims to investigate the fertility- and menopause-related information needs of younger women with a diagnosis of early breast cancer. A retrospective qualitative methodology was chosen. Twenty-four women aged between 26 and 45 years at diagnosis participated in focus group interviews and telephone interviews. Many women thought that the information they had received in the past about fertility and menopausal symptoms was either insufficient or unavailable. Some women felt that, while information on fertility and menopause issues had not been paramount at the time of diagnosis, it became increasingly important after diagnosis. Participants spoke about the need to revisit or review fertility- and menopause-related information with their doctors during the course of treatment. Many women believed that information about fertility should be given prior to or during treatment decision-making, and that information related to the management of menopausal symptoms should be delivered during or after treatment when menopausal symptoms begin. Consultation with a fertility and/or menopause specialist-rated as the most preferred mode of receiving fertility- and menopause-related information. Clinical implications are drawn from the results of this study to assist clinicians and researchers to improve their communication with younger patients about the fertility- and menopause-related side effects of breast cancer treatment.

Manifestaciones orales y manejo odontológico durante la menopausia / Oral manifestations and dental treatment in menopause

La menopausia es un proceso fisiológico que acontece en la quinta década de la mujer y en el que tiene lugar el cese permanente de la menstruación. Este proceso tiene como base unos cambios hormonales que tendrán como consecuencia una serie de manifestaciones clínicas de tipo general que han cobrado especial importancia por el aumento de la esperanza de vida en la mujer, lo que significa que la mayoría de estas mujeres padecerán dichos síntomas durante la última tercera parte de su vida. Sin embargo, no son sólo los síntomas generales (sofocos y alteraciones psicológicas) los que se manifiestan en la mujer menopaúsica, sino que también se producen síntomas a nivel oral. Así pues, existe un aumento en la incidencia de xerostomía, afecciones como el liquen plano, el penfigoide benigno, el síndrome de Sjögren, el conocido síndrome de ardor bucal y la discutida prevalencia de enfermedades periodontales. El manejo odontológico de estas pacientes presenta ciertas peculiaridades que deben ser consideradas, tales como el empleo de estimulantes de la secreción salival o de sustitutivos de la saliva en el caso de la hiposialía. No obstante, una correcta prevención, con un buen control de placa bacteriana, disminuirá los riesgos de aparición de muchas de las infecciones a nivel oral (AU)

131I therapy for differentiated thyroid cancer leads to an earlier onset of menopause: results of a retrospective study.

Treatment with 131I for differentiated thyroid cancer may give a follicle-damaging radiation dose to the ovaries. This damage to the ovarian function could shorten the fertile life span and advance the natural menopause. To address this issue, we studied retrospectively the menopausal age of 130 women treated with 131I for differentiated thyroid cancer in our institution from 1974-1993. The menopausal age of women treated with 131I for differentiated thyroid cancer after total thyroidectomy and subjected to suppressive L-T4 therapy was compared with the menopausal age of a control group including 127 goitrous women who were treated with suppressive L-T4 for a comparable period of time. The cumulative therapeutic 131I dose to cancer patients ranged from 1,110-40,700 MBq (mean +/- SD, 5,308 +/- 5,483 MBq; median, 3700 MBq). All patients chosen for the study were younger than 45 yr when first treated (i.e. first administration of 131I and L-T4 for cancer patients, and institution of L-T4 therapy for goitrous patients), and older than 45 yr at the end of the study period. The menopausal status of both groups was assessed from the clinical records and compared using Kaplan-Meier survival analysis. The menopausal age of cancer women treated with 131I and suppressive L-T4 therapy was less than that of goitrous patients treated with suppressive L-T4 therapy (P < 0.001). We could not detect any relationship between menopausal age and the age at the first or last 131I dose or to the cumulative 131I dose received. These data indicate that 131I treatment is probably associated with an earlier ovarian failure in thyroid cancer patients. Conceivably, the ovarian irradiation by 131I might contribute to the process of the follicular atresia, thus inducing earlier menopause.

Ultrasound localization of the ovaries for radiation-induced ovarian ablation.

The case notes and simulator films were reviewed from 70 sequential patients who received pelvic irradiation to induce an early menopause as part of their treatment for breast cancer at the Staffordshire Oncology Centre. These patients underwent ultrasound localization of the ovaries immediately prior to simulation. Altogether, 128 ovaries were plotted on a diagrammatic representation of a gynaecoid pelvis to represent their position in both craniocaudal and lateral dimensions in relation to the true bony pelvis. The craniocaudal ovarian position varied from 2.5 cm above the lower aspect of the sacroiliac joint to 2.0 cm above the symphysis pubis. Three (4.6%) right sided ovaries were within 1 cm medial to the right lateral side wall, with none lying lateral to the wall. Seventeen (26%) left sided ovaries were lying within 1 cm of the left pelvic side wall, with four of these lying outside. The limits of the pelvic fields used were from the top of the sacroiliac joint to the bottom of the symphysis pubis. Sixty-one (88%) upper borders were on or above the lower sacroiliac joint. Twenty-six (38%) and 49 (71%) fields were outside the right and left pelvic side walls respectively. This would suggest that field sizes were larger than standard; however, 87% were smaller than 150 cm(2) (assuming a 10x15-cm field as standard). Only one patient failed to respond to treatment. This was thought to be due to underdosing rather than a geographical miss. This patient was successfully retreated. The authors advocate the use of ultrasound localization prior to planning an irradiation menopause, to ensure that the ovaries are encompassed in the pelvic field, thus preventing a geographical miss and reducing field sizes.

Artificial radiation menopause: where are the ovaries?

For ovarian ablation using radiotherapy, the pelvis is irradiated using generous fields sizes, as the position of the ovaries is uncertain. To assess the variation in ovarian position, we reviewed 81 sequential CT examinations of the pelvis performed in women under the age of 50 years. Women with pelvic malignancy or previous pelvic surgery were excluded from the analysis, leaving 30 eligible women. One or both ovaries could be clearly identified in 23 of these patients; in 19 (83%), the ovaries were located within the upper two-thirds of a ring defined by the sacroiliac joints, the bony side wall of the pelvis and the symphysis pubis. The ovaries were located outside this ring in four (17%) women. Ovarian position did not appear to be influenced by parity, uterine orientation, the degree of bladder filling or faecal loading within the rectum. The treatment volume for artificial radiation menopause has been variably defined; the upper part of the pelvis may not be included. The results from this retrospective study suggest that the treatment volume should extend from the inferior border of the fifth lumbar vertebra down to a level traversing the middle of the femoral heads and 1 cm lateral to the pelvic side walls.

Adjuvant tamoxifen for operable carcinoma of the breast: report of clinical trial by the Christie Hospital and Holt Radium Institute.

A large controlled clinical trial with the admission of 1005 patients was carried out using tamoxifen as adjuvant treatment for women with operable carcinoma of the breast. Results were analysed for the first 906 evaluable patients randomised up to December 1981. After mastectomy premenopausal women were randomised to receive either an irradiation menopause or tamoxifen 20 mg daily for one year. Postmenopausal women were randomised to receive either tamoxifen 20 mg daily for one year or no systemic treatment (controls). Analysis at five years suggested that for premenopausal women there was no significant difference between an irradiation menopause and tamoxifen in terms of survival, local recurrence, or distant metastases. Tamoxifen had no appreciable side effects. For postmenopausal women there was a trend in favour of tamoxifen with regard to survival and incidence of distant metastases, and the difference became statistically significant for those patients with four or more positive axillary nodes. If long term results of these studies show only an improved quality of remaining life with tamoxifen, then this drug could be an important contribution to adjuvant treatment.

Leukemia and other cancers following radiation treatment of pelvic disease.

Follow-up studies of patients treated for cancer of the cervix with radiotherapy have shown such women to be at little or no increased risk of leukemia subsequent to the radiation exposure. However, women exposed to lower doses of radiation in the pelvic area, in the induction of an artificial menopause, appear to show increased risks of both leukemia and cancers of those sites directly in the radiation field. The studies of these two types of radiation exposure are reviewed. The findings may possibly be reconciled with each other on the basis of the distribution of radiation dose to the bone marrow. Irradiation for cancer of the cervix delivers radiation doses to a small portion of the marrow which are probably lethal for most marrow cells. The mean dose to cells distant from the cervix may be too small to produce a detectable increase in leukaemia incidence. The lower and more uniformly distributed radiation dose used to induce an artificial menopause will be less lethal for marrow cells and may consequently deliver a higher "effective" marrow dose to surviving--cells, resulting in an increased leukemia risk.