Disparities in Study Inclusion and Screening Rates in Breast Cancer Screening Rates among Transgender People: A Systematic Review.

BACKGROUND: Breast cancer screening trends of transgender and gender diverse (TGD) people remain largely unknown. This is concerning, as data is necessary to inform recommendations made by clinicians to their patients and by national guidelines to clinicians. The aim of this review is to explore the state of existing research literature and provide a summary report of current breast cancer screening rates in TGD adults. METHODS: All articles were identified using Medical Subject Headings (MeSH) terms Inclusion criteria were all the following: 1) Documents inclusion of at least one participant who identifies as a TGD person; 2) At least one TGD participant with top-surgery or currently receiving estrogen-based gender affirming hormone therapy (GAHT); 3) Results report rates of breast cancer screening or mammogram referral. RESULTS: Twelve articles met inclusion criteria, six cross-sectional studies and six retrospective chart reviews. Three studies conducted secondary analysis of the Behavioral Risk Factor Surveillance System (BRFSS) national dataset, and nine articles recruited their own sample with TGD participant ranges from 30 to 1,822 and cisgender women ranges from 242 to 18,275. Three studies found lower rates of screening in transfeminine persons receiving gender-affirming care compared to cisgender women; two studies found lower rates among TGD people compared to cisgender women; and three studies found no differences between the breast cancer screening rates of TGD and cisgender participants. CONCLUSION: Limited studies recruit and report trends in breast cancer screening of TGD people. Those that do include TGD participants have mixed results, but overall TGD people had lower rates of breast cancer screening. More research is needed regarding breast cancer screening of TGD people to inform the development of protocols that ensure equitable access to preventative care.

The effect of genetic variation in estrogen transportation and metabolism on the severity of menopause symptoms: A study from the RIGHT 10K cohort.

OBJECTIVE: The severity of menopause-related symptoms varies considerably among women. The determinants of this variation are incompletely understood. The aim of this study was to assess the association between genetic variation in estrogen metabolism and transport pathways and the severity of menopause symptoms. METHODS: This was a cross-sectional study of 60 peri- and postmenopausal women in the Mayo Clinic RIGHT study (which involved sequencing of genes involved in drug metabolism and transport), who had also been evaluated in the Women's Health Clinic at Mayo Clinic in Rochester, MN. All participants completed the Menopause Rating Scale (MRS) for assessment of menopause symptoms, including hot flashes. The association between severity of menopause symptoms and the variation in genes encoding 8 enzymes and transporters involved in estrogen metabolism was evaluated. RESULTS: Lower CYP3A4 activity and higher COMT activity were associated with lower severity of somatic menopause symptoms (p = 0.04 and 0.06, respectively). These associations did not persist after adjustment for hormone therapy use. No differences in MRS scores or hot flash severity were noted among other genetic variant groups. Age at natural menopause was not affected by variations in the genes studied. CONCLUSION: The current study did not show an association between genetic variation in estrogen metabolism and transport pathways and the severity of menopause symptoms. Further studies with larger sample sizes may be required to understand this potentially complex association.

Menopausal Hormone Therapy in Older Women: Examining the Current Balance of Evidence.

Menopause occurs in all women. During the menopause transition, 80% of women experience vasomotor symptoms that can last an average of 7-10 years or longer, sometimes into the seventh and eighth decades of life. Understanding how to manage vasomotor symptoms (VMS) in older menopausal women is important since these symptoms can negatively impact quality of life. This review provides a practical guide on how to approach VMS treatment either with menopausal hormone therapy or non-hormone options. When initiating, as well as continuing hormone therapy, the factors clinicians should consider as they weigh risks and benefits include assessing a woman's risks related to cardiovascular disease, breast cancer, and osteoporosis. Utilizing a shared decision-making approach in regard to menopausal symptom management should aim to support women and help them maintain health and quality of life.

Associations between pituitary-ovarian hormones and cognition in recently menopausal women independent of type of hormone therapy.

OBJECTIVES: To examine associations of pituitary-ovarian hormone levels with cognition before and after different formulations of hormone therapy (HT) or placebo independent of treatment group. METHODS: Recently menopausal, healthy women were randomized to 0.45 mg/day oral conjugated equine estrogens (o-CEE, n = 109), 50 µg/day transdermal 17ß (tE2, n = 107) or placebo pills and patches (n = 146); women on active treatment received oral 200 mg/day micronized progesterone for 12 days per month. Levels of estrone, 17ß-estradiol, follicle stimulating hormone, luteinizing hormone, androstenedione, and testosterone were determined prior to and after 48 months of study participation. Neuropsychological testing was administered at baseline, and months 18, 36 and 48. Latent growth curve models controlling for education level, age, APOE allele status, waist circumference, and treatment examined the trajectories of each cognitive domain after accounting for the effect of hormone levels at baseline and months 18, 36 and 48. A linear multivariate mixed model examined the effect of changes in hormone levels on changes in trajectories of complex attention tasks with varying degrees of difficulty. RESULTS: All women were adherent to treatment at month 48. Higher baseline estrone levels were associated with poorer global cognition, auditory attention and working memory, visual attention, and executive function, but not working memory. Higher levels of baseline 17ß-E2 were associated with poorer cognitive performance, with marginal significance at baseline in speeded language and mental flexibility (p = 0.013). Other hormone levels were not associated with cognition. Controlling for all treatments, hormone levels at baseline and at month 48 did not have any significant correlation with cognitive trajectories over time. SUMMARY: In healthy, recently menopausal women, baseline estrone levels were inversely associated with selected cognitive factors independent of two types of HT or placebo during 4 years of follow-up. Baseline levels of the other pituitary-ovarian hormones studied were not associated with baseline cognition, nor were changes in any hormones associated with changes in cognition during the study. The marginal association between estradiol levels and cognitive factors warrants further investigation. GOV NUMBERS: NCT00154180, NCT00623311.

Sexual Health Update in Women.

The Clinical Update series is intended to help busy clinicians stay up to date with recently published important and potentially practice-changing articles on topics pertinent to the care of women. In this update on sexual health, we review studies on use of vaginal dilators for vaginal stenosis in gynecologic cancer survivors, sexual dysfunction in transgender people, as well as studies evaluating the effect of physical activity and infertility on female sexual health.

Association of breast cancer risk, density, and stiffness: global tissue stiffness on breast MR elastography (MRE).

PURPOSE: Quantify in vivo biomechanical tissue properties in various breast densities and in average risk and high-risk women using Magnetic Resonance Imaging (MRI)/MRE and examine the association between breast biomechanical properties and cancer risk based on patient demographics and clinical data. METHODS: Patients with average risk or high-risk of breast cancer underwent 3.0 T breast MR imaging and elastography. Breast parenchymal enhancement (BPE), density (from most recent mammogram), stiffness, elasticity, and viscosity were recorded. Within each breast density group (non-dense versus dense), stiffness, elasticity, and viscosity were compared across risk groups (average versus high). Separately for stiffness, elasticity, and viscosity, a multivariable logistic regression model was used to evaluate whether the MRE parameter predicted risk status after controlling for clinical factors. RESULTS: 50 average risk and 86 high-risk patients were included. Risk groups were similar in age, density, and menopausal status. Among patients with dense breasts, mean stiffness, elasticity, and viscosity were significantly higher in high-risk patients (N = 55) compared to average risk patients (N = 34; all p < 0.001). Stiffness remained a significant predictor of risk status (OR = 4.26, 95% CI [1.96, 9.25]) even after controlling for breast density, BPE, age, and menopausal status. Similar results were seen for elasticity and viscosity. CONCLUSION: A structurally based, quantitative biomarker of tissue stiffness obtained from MRE is associated with differences in breast cancer risk in dense breasts. Tissue stiffness could provide a novel prognostic marker to help identify high-risk women with dense breasts who would benefit from increased surveillance and/or risk reduction measures.

A Comparison of Perceived Lifetime Breast Cancer Risk to Calculated Lifetime Risk Using the Gail Risk Assessment Tool.

Background: Understanding the accuracy of a woman's perceived breast cancer risk can enhance shared decision-making about breast cancer screening through provider and patient discussion. We aim to report and compare women's perceived lifetime breast cancer risk to calculated lifetime breast cancer risk. Methods: Women presenting to Mayo Clinic in Arizona and Minnesota in July 2016 completed a survey assessing their perceived breast cancer risk. Lifetime Gail risk scores were calculated from questions pertaining to health history and were then compared with perceived breast cancer risk. Results: A total of 550 predominantly white, married, and well-educated (≥college) women completed surveys. Using lifetime Gail risk scores, 5.6% were classified as high risk (>20% lifetime risk), 7.7% were classified as intermediate risk (15%-20%), and 86.6% were classified as average risk (<15%). Of the 27 women who were classified as high risk, 18 (66.7%) underestimated their risk and of the 37 women who were intermediate risk, 12 (32.4%) underestimated risk. Women more likely to underestimate their risk had a reported history of an abnormal mammogram and at least one or more relative with a history of breast cancer. Surveyed women tended to overestimate risk 4.3 (130/30) times as often as they underestimated risk. Conclusion: In a group of predominantly white, educated, and married cohort of women, there was a large portion of women in the elevated risk groups who underestimated risk. Specific aspects of medical history were associated with underestimation including a history of abnormal mammogram and family history of breast cancer. Overall, in our sample, more women overestimated than underestimated risk.

The Dense Breast Clinic: Initial Experience of a Patient-Centered Breast Imaging Clinic.

OBJECTIVE: Establish a radiologist-run consultation clinic to review breast density and supplemental screening exams (SSEs) directly with patients in response to breast density reporting laws. METHODS: Breast radiologists opened and staffed a clinic for formal patient consultations regarding breast density and SSEs. An IRB-approved questionnaire assessed patient knowledge of breast density, SSEs, and encounter satisfaction. Comparative statistical analyses were performed on knowledge-based questions. RESULTS: From February 2019 to February 2021, 294 reimbursable consultations were performed with 215 patients completing pre- and post-consultation questionnaires (survey response rate, 73%). Median patient age was 58 years (range, 34-86 years) and 9% (19/210) had a personal history of breast cancer. An increase in patient knowledge of breast density and SSEs was observed as follows: breast density categories (9% correct pre-consultation (20/215), 86% correct post-consultation (185/215), P < 0.001), dense breast effects on cancer risk (39% correct pre-consultation (83/215), 84% post-consultation (180/215)), mammogram sensitivity (90% correct pre-consultation (193/215), 94% post-consultation (201/215)), and increased cancer detection with SSEs (82% correct pre-consultation (177/215), 95% post-consultation (205/215)) (P < 0.001). Post-consultation, 96% (200/209) were satisfied with the usefulness of information, 89% (186/209) strongly agreed they had sufficient knowledge of SSEs, and 81% (167/205) agreed they would like future opportunities to meet with a breast radiologist. CONCLUSION: A consultation clinic staffed by breast radiologists focused on breast density and supplemental breast cancer screening can provide personalized patient counseling, engage patients in shared decision making, assist referring clinicians, and support high quality patient-centered care.

Supplemental Cancer Screening for Women With Dense Breasts: Guidance for Health Care Professionals.

Mammography is the standard for breast cancer screening. The sensitivity of mammography in identifying breast cancer, however, is reduced for women with dense breasts. Thirty-eight states have passed laws requiring that all women be notified of breast tissue density results in their mammogram report. The notification includes a statement that differs by state, encouraging women to discuss supplemental screening options with their health care professionals (HCPs). Several supplemental screening tests are available for women with dense breast tissue, but no established guidelines exist to direct HCPs in their recommendation of preferred supplemental screening test. Tailored screening, which takes into consideration the patient's mammographic breast density and lifetime breast cancer risk, can guide breast cancer screening strategies that are more comprehensive. This review describes the benefits and limitations of the various available supplemental screening tests to guide HCPs and patients in choosing the appropriate breast cancer screening.

Menopausal hormone therapy in women with medical conditions.

Hormone therapy is the most effective treatment for menopause-related symptoms. Current evidence supports its use in young healthy postmenopausal women under the age of 60 years, and within 10 years of menopause, with benefits typically outweighing risks. However, decision making is more complex in the more common clinical scenario of a symptomatic woman with one or more chronic medical conditions that potentially alter the risk-benefit balance of hormone therapy use. In this review, we present the evidence relating to the use of hormone therapy in women with chronic medical conditions such as obesity, hypertension, dyslipidemia, diabetes, venous thromboembolism, and autoimmune diseases. We discuss the differences between oral and transdermal routes of administration of estrogen and the situations when one route might be preferred over another. We also review evidence regarding the effect of different progestogens, when available.

Associations of pituitary-ovarian hormones and white matter hyperintensities in recently menopausal women using hormone therapy.

OBJECTIVE: Little is known about how menopausal hormone treatment (HT) may influence the development of white matter hyperintensities (WMHs) in the brain. This study evaluated the associations of changes in levels of pituitary-ovarian hormones during HT and changes in WMH. METHODS: Women (n = 78 adherent to treatment) enrolled in the Kronos Early Estrogen Prevention Study underwent brain magnetic resonance imaging, and blood collection before and after 48 months of randomization to 0.45 mg/d oral conjugated equine estrogen (oCEE) daily, 50 µg/d transdermal 17ß estradiol (tE2), or placebo pills and patches. Women in the active treatment groups also received oral 200 mg/d micronized progesterone the first 12 days of the month. Estradiol (E2), estrone (E1), follicle-stimulating hormone (FSH), and luteinizing hormone (LH) were measured in serum by high sensitivity liquid chromatography/mass spectrometry at baseline and following 48 months of HT. Longitudinal change in WMH volume was determined from fluid-attenuated inversion recovery magnetic resonance imaging using a semiautomated image segmentation algorithm. RESULTS: Serum levels of FSH, LH, E1, or E2 did not associate with WMH volume at baseline. After 48 months of treatment, smaller increases in WMH associated with decreases in FSH from baseline in the tE2 group and increases in E1 in both tE2 and oCEE groups. Changes in LH did not associate with changes in WMH in any group. CONCLUSIONS: Circulating levels of pituitary-ovarian hormones associate with changes in WMH volume in recently menopausal women using HT. Whether these relationships would be influenced by different doses of tE2 or oCEE remains to be determined. : Video Summary:http://links.lww.com/MENO/A590.

Video Summary:http://links.lww.com/MENO/A590.

Transdermal delivery of bioidentical estrogen in menopausal hormone therapy: a clinical review.

Introduction: The history of menopausal hormone therapy (HT) use has evolved over the years based on the influence of many factors, including availability and safety related to formulation and route of estrogen products. Given unexpected findings from the Women's Health Initiative (WHI) in the early 2000's that used oral conjugated equine estrogen, the desire for and research supporting transdermal estradiol products grew. Transdermal estrogen is now a popular and commonly used formulation for treating menopausal symptoms. Many FDA approved products are available and preferred to custom compounded bioidentical products given superior consistency and safety standards.Areas covered: This review explores the history of transdermal estrogen products, as well as their pharmacodynamics. It also includes a detailed exploration of the advantages and disadvantages of different estrogen formulations with a focus on clinically useful information.Expert opinion: FDA approved transdermal estradiol products are the preferred formulation and route for HT, along with a progestogen for women with a uterus, given their efficacy and superior safety profile.

Androgen Therapy in Women.

Androgens are believed to have an important biologic role in women, particularly in regulation of libido and sexual arousal, although much about their function on other systems in women is unknown. Testosterone, the primary ovarian androgen, has been used to treat carefully selected postmenopausal women with hypoactive sexual desire disorder (HSDD). However, testosterone use in women has not been approved by the United States Food and Drug Administration (FDA) because of uncertainties regarding the effectiveness and long-term safety of this strategy. An intravaginal form of the adrenal androgen, dehydroepiandrosterone (DHEA) has been approved by the FDA to treat genitourinary syndrome of menopause. In this article, we review the current knowledge regarding the role of androgens and their clinical use in women. We conducted a systematic search of PubMed for publications describing the role and clinical use of androgens in women. We used the search terms "HSDD," "DHEA in women," "testosterone in women," and "androgens in women," and reviewed most references from all relevant articles. Most randomized placebo-controlled trials show an improvement in sexual function with low-dose testosterone therapy in select postmenopausal women with HSDD. Although this strategy appears to be safe in the short term and no major safety concerns have emerged thus far, long-term effects on cardiovascular risk and breast cancer incidence are not known. A trial of low-dose testosterone therapy may be considered for carefully selected postmenopausal women with HSDD, as long as other contributors to sexual dysfunction have been adequately addressed. However, patients need careful counseling regarding the lack of long-term safety data, and close clinical and laboratory monitoring of these women is recommended to avoid supraphysiologic dosing.

Impact of menopausal hormone formulations on pituitary-ovarian regulatory feedback.

Changes in pituitary-ovarian hormones across the menopausal transition have multiple physiological consequences. However, little is known about how the major types of postmenopausal hormone therapy (HT) affect pituitary-ovarian hormonal relationships. This study evaluated these relationships in recently menopausal women (52.45 ± 2.49 yr of age) in the Kronos Early Estrogen Prevention Study (KEEPS) who were compliant to randomized, double-blinded treatment with oral conjugated equine estrogen (o-CEE; n = 109), transdermal 17ß-estradiol (t-E2; n = 107), or placebo (n = 146). Androstenedione, testosterone, 17ß-estradiol, estrone, follicle-stimulating hormone (FSH), and luteinizing hormone (LH) were measured in serum before (baseline) and 48 mo after randomization to treatment. Descriptive summaries of hormone levels were performed, and multiple regression analyses were used to examine the effects of o-CEE, t-E2, and placebo on these hormone levels at 48 mo, adjusting for baseline levels. A network analysis examined the covariance of changes in hormone levels over the 48 mo within treatment groups. As expected, at 48 mo of treatment, hormone levels differed between women in the two active treatment groups compared with placebo, and network analysis indicated stronger relationships among hormone levels in the t-E2 and o-CEE groups compared with placebo. Associations among testosterone, 17ß-estradiol, FSH, and LH differed between the o-CEE group compared with t-E2 and placebo groups. Thus, two common HT regimens differentially alter pituitary-ovarian hormone levels, altering feedback cycles and interhormonal associations in recently menopausal women. These interactions provide the basis for future studies investigating the impact of hormonal modulation of aging, including cognitive decline in women.