Successful Retirement Planning for Endocrinologists.

The Endocrine Society formally addressed the issue of retirement for its members for the first time in a Workshop held on June 4 at ENDO 2024 in Boston, Massachusetts. Preparation for the workshop included 4 steps: (1) completion of a survey; (2) advice from a retirement expert; (3) extensive literature review; and (4) multiple pre-workshop discussions among the presenters. The survey found that retired endocrinologists are involved in a wide variety of professional and nonprofessional activities.

Role of ERα and Aromatase in Juvenile Gigantomastia.

Context: Approximately 150 patients with juvenile gigantomastia have been reported in the literature but the underlying biologic mechanisms remain unknown.

Objective: To conduct extensive clinical, biochemical, immunochemical, and genetic studies in 3 patients with juvenile gigantomastia to determine causative biologic factors.

Methods: We examined clinical effects of estrogen by blockading estrogen synthesis or its action.

Intensive, telemedicine-based, self-management program for rural, underserved patients with diabetes mellitus: Re-entry of retired endocrinologists into practice.

Introduction: Endocrinology workforce data demonstrate a substantial gap in the number of practicing endocrinologists, a phenomenon particularly affecting patients with diabetes in rural, financially challenged, underserved areas. We evaluated the concept that retired endocrinologists could re-enter practice part time and utilize telemedicine in collaboration with personnel in Federally Qualified Community Health Center clinics to conduct an intensive self-management program and provide 6-month concurrent care for patients with diabetes.

Methods: The program involved intensive glucose control measures and education in diabetes, nutrition, and lifestyle changes over a 6-month period.

Mechanistic Effects of Estrogens on Breast Cancer.

Purpose: Current concepts regarding estrogen and its mechanistic effects on breast cancer in women are evolving. This article reviews studies that address estrogen-mediated breast cancer development, the prevalence of occult tumors at autopsy, and the natural history of breast cancer as predicted by a newly developed tumor kinetic model.

Methods: This article reviews previously published studies from the authors and articles pertinent to the data presented.

Approach to the Patient With New-Onset Secondary Amenorrhea: Is This Primary Ovarian Insufficiency?

Menstrual cyclicity is a marker of health for reproductively mature women. Absent menses, or amenorrhea, is often the initial sign of pregnancy-an indication that the system is functioning appropriately and capable of generating the intended evolutionary outcome. Perturbations of menstrual regularity in the absence of pregnancy provide a marker for physiological or pathological disruption of this well-orchestrated process.

Approach to Managing a Postmenopausal Patient.

The case of a symptomatic, postmenopausal woman is presented and a full discussion of the approach to her management is discussed. Pertinent guidelines and scientific evidence are emphasized as support for the recommendations.

Workshop on normal reference ranges for estradiol in postmenopausal women, September 2019, Chicago, Illinois.

The North American Menopause Society (NAMS) organized the Workshop on Normal Ranges for Estradiol in Postmenopausal Women from September 23 to 24, 2019, in Chicago, Illinois. The aim of the workshop was to review existing analytical methodologies for measuring estradiol in postmenopausal women and to assess existing data and study cohorts of postmenopausal women for their suitability to establish normal postmenopausal ranges. The anticipated outcome of the workshop was to develop recommendations for establishing normal ranges generated with a standardized and certified assay that could be adopted by clinical and research communities.

Underlying Breast Cancer Risk and Menopausal Hormone Therapy.

The recent Collaborative Group on Hormonal Factors in Breast Cancer (CGHFBC) publication calculated the attributable risk of breast cancer from use of estrogen alone and estrogen plus a synthetic progestogen for less than 5 to 15 or more years of use. This CGHFB report calculated attributable risk based on their findings of relative risk from pooled data from 58 studies. Notably, neither the CGHFBC nor other previous studies have examined the effect of underlying risk of breast cancer on attributable risk.

Systemic estradiol levels with low-dose vaginal estrogens.

Objectives: To critically evaluate published systemic estradiol levels during use of low-dose vaginal estrogens considering detection method and estrogen dose; describe challenges with accurately measuring estradiol; and determine the normal estradiol level range in postmenopausal women.

Methods: PubMed was searched for studies reporting systemic estradiol levels with lower-dose vaginal estrogens (≤25 μg estradiol or 0.3 mg conjugated equine estrogens).

Pro-Apoptotic Effects of Estetrol on Long-Term Estrogen-Deprived Breast Cancer Cells and at Low Doses on Hormone-Sensitive Cells.

Purpose: Postmenopausal women with estrogen receptor-positive breast cancers often respond initially to tamoxifen or aromatase inhibitor therapy. Resistance to these treatments usually develops within 12 to 18 months. Clinical studies have demonstrated that high-dose estrogen can induce regression of these endocrine-resistant tumors.

History of Estrogen: Its Purification, Structure, Synthesis, Biologic Actions, and Clinical Implications.

This mini-review summarizes key points from the Clark Sawin Memorial Lecture on the History of Estrogen delivered at Endo 2018 and focuses on the rationales and motivation leading to various discoveries and their clinical applications. During the classical period of antiquity, incisive clinical observations uncovered important findings; however, extensive anatomical dissections to solidify proof were generally lacking. Initiation of the experimental approach followed later, influenced by Claude Bernard's treatise "An Introduction to the Study of Experimental Medicine.

Glucocorticoid Receptor Mutations and Hypersensitivity to Endogenous and Exogenous Glucocorticoids.

Background: The glucocorticoid receptor (GR) consists of two alternatively spliced isoforms: GRα, which activates gene transcription, and GRβ, a dominant-negative receptor. Theoretically, inactivating variants of GRβ could result in glucocorticoid hypersensitivity.

Design: A 46-year-old woman presented for evaluation of adrenal insufficiency prompted by low plasma cortisol levels and multiple unexplained symptoms but without clinical evidence of glucocorticoid insufficiency.

Effect of a tissue selective estrogen complex on breast cancer: Role of unique properties of conjugated equine estrogen.

The Women's Health Initiative studies reported that the menopausal hormone therapy (MHT) regimen containing conjugated equine estrogen (CEE) and medroxyprogesterone acetate increased, whereas CEE alone reduced breast cancer incidence. These observations suggest the possibility that CEE might exert unique actions on breast and also suggest the need to eliminate the progestogen from MHT regimens. A MHT regimen called a tissue selective estrogen complex (TSEC), containing CEE plus bazedoxifene (BZA), to avoid the need for a progestogen, was developed and FDA approved.

Estrogen Replacement in Turner Syndrome: Literature Review and Practical Considerations.

Context: Most girls with Turner syndrome (TS) have hypergonadotropic hypogonadism and need hormonal replacement for induction of puberty and then for maintaining secondary sex characteristics, attaining peak bone mass, and uterine growth. The optimal estrogen replacement regimen is still being studied.

Evidence Acquisition: We conducted a systematic search of PubMed for studies related to TS and puberty.

The Jewel in the Crown: Specific Aims Section of Investigator-Initiated Grant Proposals.

The specific aims section of National Institutes of Health and other grants is the most important component, as it summarizes the scientific premise, gap in current knowledge, hypotheses, methods, and expected results of the project proposed. The reviewer usually reads this section first and forms an immediate opinion, usually confirmed on reading the entire grant. This treatise reviews the philosophical background underlying generation of hypotheses, emphasizes the important characteristics of the specific aims section, and offers a point-by-point roadmap for writing.

Managing Menopausal Symptoms and Associated Clinical Issues in Breast Cancer Survivors.

Objective: Review evidence to guide management of menopausal signs and symptoms in women after breast cancer and make recommendations accordingly.

Evidence: Randomized controlled clinical trials, observational studies, evidence-based guidelines, and expert opinion from professional societies.

Background: Symptoms and clinical problems associated with estrogen depletion-sleep disorders, vulvovaginal atrophy (VVA), vasomotor symptoms (VMS), mood changes, depressive symptoms, cardiovascular disease, osteopenia, and osteoporosis-confront the estimated 9.

Use of cardiovascular age for assessing risks and benefits of menopausal hormone therapy.

The Women's Health Initiative studies and others have suggested that menopausal hormone therapy may enhance the risk of new cardiovascular (CV) events in older women and diminish the development of coronary atherosclerosis in younger women. The underlying mechanisms to explain these findings are encapsulated in the term "Timing Hypothesis." Extensive pathophysiologic studies have provided mechanistic evidence for the dichotomous effects of estrogen on coronary artery vasculature.

Career Advancement: Meeting the Challenges Confronting the Next Generation of Endocrinologists and Endocrine Researchers.

Context: Challenges and opportunities face the next generation (Next-Gen) of endocrine researchers and clinicians, the lifeblood of the field of endocrinology for the future. A symposium jointly sponsored by The Endocrine Society and the Endocrine Society of Australia was convened to discuss approaches to addressing the present and future Next-Gen needs.

Evidence Acquisition: Data collection by literature review, assessment of previously completed questionnaires, commissioning of a new questionnaire, and summarization of symposium discussions were studied.

Progression of Metabolic Syndrome Severity During the Menopausal Transition.

Background: After menopause, women exhibit a higher prevalence of the metabolic syndrome (MetS) and higher risk of cardiovascular disease. However, the timing of changes in MetS severity over the menopausal transition and whether these changes differ by racial/ethnic group remain unclear.

Methods And Results: We assessed data from 1470 women from the Atherosclerosis Risk in Communities cohort who experienced transition in menopausal status over 10 years (visits 1-4).

Preclinical breast effects of a tissue selective estrogen complex (TSEC) including conjugated estrogen with bazedoxifene.

The first tissue-selective estrogen complex (TSEC), consisting of a combination of a conjugated equine estrogen (CEE) and bazedoxifene (BZA), has been approved for treatment of the menopause in the USA and European Union. We have postulated that this TSEC might block the estrogenic effects of CEE on breast tissue and thereby prevent breast cancer growth. This manuscript, representing a presentation at a Festschrift honoring Evan Simpson, reviews our published data BZA blocked the in vitro effects of both estradiol and CEE on cell growth and gene expression in MCF-7 cells.

An introduction to the Endocrine Society Clinical Practice Guideline on treatment of symptoms of the menopause.

Treatment of symptoms of menopause remains a challenge for many health care practitioners. In an effort to facilitate this process, the Endocrine Society convened an international Task Force of menopause experts to review the relevant clinical evidence and formulate practical recommendations for relieving the most common menopausal symptoms. The result is a comprehensive evidence-based guideline, which emphasizes an individualized approach to alleviate bothersome vasomotor symptoms and those related to postmenopausal changes of the vagina and urinary tract.

Treatment of Symptoms of the Menopause: An Endocrine Society Clinical Practice Guideline.

Objective: The objective of this document is to generate a practice guideline for the management and treatment of symptoms of the menopause.

Participants: The Treatment of Symptoms of the Menopause Task Force included six experts, a methodologist, and a medical writer, all appointed by The Endocrine Society.

Evidence: The Task Force developed this evidenced-based guideline using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system to describe the strength of recommendations and the quality of evidence.