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BACKGROUND: As a growing percentage of Americans will be reaching their elderly years in the next decade, the prevalence of osteoporosis and its effects will have an even greater impact on the healthcare system. Advancements in bone research and development of newer treatments have allowed for the establishment of more refined guidelines and a growing awareness of the need to prevent, screen, and diagnose osteoporosis. Thus, more women are now being screened with dual x-ray absorptiometry scans (DXA) than ever before. The importance of a true understanding of the test results obtained from such screening is paramount. In our institution, recommendations to consider a secondary evaluation are made by the DXA interpreters when the Z-score is low. Few, if any, studies have evaluated the rates of physician and patient adherence with specific recommendations provided on the bone density report. METHODS: To assess compliance with such recommendations provided in DXA interpretations, we investigated the number of ordering providers who actually pursued these advisements. RESULTS: We found that among providers ordering DXAs, primary care providers did not pursue recommendations to pursue a secondary workup as often as their subspecialty counterparts. We also found a significant amount of vitamin D deficiency/insufficiency and primary hyperparathyroidism in the population evaluated. CONCLUSIONS: Primary care providers should be further educated on treatable secondary causes of osteoporosis as opposed to an often reflexive response of prescribing a pharmacological antiresportive agent without other consideration. [ABSTRACT FROM AUTHOR]

Shared medical appointments (SMAs) are a new way to deliver woman-focused interdisciplinary care for midlife women. SMAs are a series of one physician to one patient encounters with other patient observers. The women's health physician addresses each woman's unique medical needs individually but in the context of a shared setting. The major focus is on delivering individual medical care with the benefits of additional time spent educating women patients and answering questions. [ABSTRACT FROM AUTHOR]

Every woman, if she lives long enough, will transition into menopause, and as the US population ages, women will be spending more time in a postmenopausal state than before. For postmenopausal women, the decision to initiate menopausal hormone therapy should be individualized. A thorough evaluation of the patient's cardiovascular, venous thromboembolic, cancer, and fracture risk should be considered along with the woman's quality of life. Hormone therapy exerts its therapeutic effects on vasomotor symptoms, the skeleton, and the genitourinary system independent of age since menopause and these benefits are lost once hormone therapy is stopped. Here we review the pharmacologic properties dose, formulation, mode of administration, timing of initiation, and duration of hormonal therapies in regard to optimizing benefit and minimizing risk to the patient. This discussion will focus on the effects of common hormonal therapies including estrogen (local and systemic), progesterone, estrogen receptor agonist/antagonist, and local dehydroepiandrosterone and include a brief review of compounded bioidentical hormone therapy., (© 2020, The American College of Clinical Pharmacology.)

Patients with breast cancer receiving antiestrogen therapy, specifically aromatase inhibitors, often suffer from vaginal dryness, itching, irritation, dyspareunia, and dysuria, collectively known as genitourinary syndrome of menopause (GSM). GSM can decrease quality of life and is undertreated by oncologists because of fear of cancer recurrence, specifically when considering treatment with vaginal estrogen therapy because of unknown levels of systemic absorption of estradiol. In this article, we review the available literature for treatment of GSM in patients with breast cancer and survivors, including nonhormonal, vaginal hormonal, and systemic hormonal therapy options. First-line treatment includes nonhormonal therapy with vaginal moisturizers, lubricants, and gels. Although initial studies showed significant improvement in symptoms, the US Food and Drug Administration recently issued a warning against CO 2 laser therapy for treatment of GSM until additional studies are conducted. In severe or refractory GSM, after discussing risks and benefits of vaginal hormonal therapy, the low-dose 10-μg estradiol-releasing intravaginal tablet or lower-dose 4 μg estrogen vaginal insert and intravaginal dehydroepiandrosterone (prasterone) are options for treatment, because studies show minimal elevation in serum estradiol levels and significant improvement in symptoms. The decision to offer vaginal estrogen therapy must be individualized and made jointly with the patient and her oncologist.

In the article by A.C. Moreno, S.K. Sikka, and H.L. Thacker, Genitourinary syndrome of menopause in breast cancer survivors: Treatments are available, Cleve Clin J Med 2018; 85(10):760-766, doi:10.3949/ccjm.85a.17108, Table 2 incorrectly stated that prasterone is contraindicated in women with known or suspected breast cancer. This correction has been made online as follows. "Warning: Estrogen is a metabolite of prasterone; use of exogenous extrogen is contraindicated in women with known or suspected breast cancer; prasterone has not been studied in women with a history of breast cancer."

When treating the genitourinary syndrome of menopause (GSM) in women with breast cancer or at high risk of breast cancer, clinicians must balance the higher cancer risks associated with hormonal treatments against the severity of GSM symptoms, which can be exacerbated by breast cancer treatments. Options for patients who need hormonal therapy include locally applied estrogens, dehydroepiandrosterone (DHEA), and estrogen receptor agonists/antagonists, which vary in their impact on breast cancer risk., (Copyright © 2018 Cleveland Clinic.)

Estrogen receptor agonist-antagonists (ERAAs) selectively inhibit or stimulate estrogen-like action in targeted tissues. This review summarizes how ERAAs can be used in combination with an estrogen or alone to treat menopausal symptoms (vasomotor symptoms, genitourinary syndrome of menopause), breast cancer or the risk of breast cancer, osteopenia, osteoporosis, and other female midlife concerns., (Copyright © 2017 Cleveland Clinic.)

Urinary incontinence is common, underreported, and undertreated. Primary care physicians should be comfortable discussing urinary incontinence with their female patients and managing it with conservative treatment., (Copyright © 2017 Cleveland Clinic.)

Purpose: To compare bone thickness buccal to the teeth in the esthetic zone of postmenopausal women, premenopausal women, younger men and older men., Methods: Retrospective data were randomly selected from 4 groups: 59 premenopausal women, 60 postmenopausal women, 60 men less than age 50, and 60 men more than 50. Half-root and bone crest landmarks were identified on each participant's cone beam computed tomography for teeth 7 to 10 and 23 to 26. Buccal bone thickness was measured by calibrated examiners. Group averages were calculated and compared between groups using analysis of variance (P < 0.05)., Results: When comparing premenopausal to postmenopausal women and postmenopausal women to older men, anterior bone thickness was significantly different for tooth maxillary and mandibular lateral incisors and overall maxillary and mandibular central incisors. In addition, significant differences were observed between these groups within the maxilla comparing lateral incisors, central incisors (P < 0.05), and within the mandible when comparing lateral and central incisors at (P < 0.05) at bone crest and half-root, respectively., Conclusion: Buccal bone in the anterior esthetic zone bone is thin in all segments of the population, but significantly thinner in postmenopausal women. In this cohort, when anterior implants are planned, it is essential to make informed treatment planning decisions. Strategies are available to manage the thinner bony housing, but require further research specific to this growing consumer cohort.

While Women's Health (WH) Fellowships have been in existence since 1990, knowledge of their existence seems limited. Specialized training in WH is crucial to educate leaders who can appropriately integrate this multidisciplinary field into academic centers, especially as the demand for providers confident in the areas of contraception, perimenopause/menopause, hormone therapy, osteoporosis, hypoactive sexual desire disorder, medical management of abnormal uterine bleeding, office based care of stress/urge incontinence, and gender-based medicine are increasing popular and highly sought after. WH fellowship programs would benefit from accreditation from the American Board of Medical Subspecialties and from the American College of Graduate Medical Education, as this may allow for greater recruitment, selection, and training of future leaders in WH. This article provides a current review of what WH trained physicians can offer patients, and also highlights the added value that accreditation would offer the field. Ultimately, accrediting WH fellowships will improve women's health medical education by creating specialists that can serve as academic leaders to help infuse gender specific education in primary residencies, as well as serve as consultants and leaders, and promote visibility and prestige of the field.

Objective: This study aims to compare periodontitis severity in postmenopausal women whose FRAX (World Health Organization Fracture Risk Assessment Tool) scores indicate a major risk for osteoporotic fracture (OPF) versus controls., Methods: Participant charts from the Case/Cleveland Clinic Postmenopausal Wellness Collaboration 853-sample database were selected based on the following inclusion criteria: (1) aged between 51 and 80 years; (2) menopause for more than 1 year but less than 10 years; (3) nonsmoker; (4) hemoglobin A1c less than 7; and (5) no glucocorticoid, hormone, RANKL (receptor activator of nuclear factor-κB ligand) inhibitor, or bisphosphonate therapy within 5 years. FRAX score was calculated, and participants were organized into two groups: women with major OPF risk (FRAX scores >20%) and controls. Periodontal data were obtained from the charts. T test was used to assess differences in periodontal parameters between groups., Results: Ninety participants had FRAX scores higher than 20% and were considered to have high OPF risk; 98 participants served as controls. Probing depth (mean [SD], 2.75 [0.66] vs 2.2 [0.57]), clinical attachment loss (3.15 [0.78] vs 2.73 [0.66]), alveolar bone height (0.58 [0.03] vs 0.60 [0.02]), and tooth loss (5.6 [1.96] vs 3.84 [1.94]) were significantly different between groups, whereas plaque score and bleeding on probing were not., Conclusions: Postmenopausal women whose FRAX scores suggest major OPF risk have significantly more severe periodontitis endpoints than controls even though oral hygiene scores do not significantly differ. These findings suggest to clinicians treating women after menopause that referral to a periodontist for disease screening may be appropriate for those women with high fracture risk based on FRAX scores.

After the publication of the Women's Health Initiative, attitudes towards management of menopausal symptoms changed dramatically. One alternative that has received much media attention is the use of bioidentical hormone therapy (BHT). The media and celebrity endorsements have promoted a number of misconceptions about the risks and benefits associated with the various forms of BHT. This article will review the available evidence regarding the safety and efficacy of BHT in comparison to conventional hormone therapy. We will also review several cases seen in our midlife women's referral clinics, which demonstrate concerns for the safety and efficacy of BHT, including unexplained endometrial cancer in otherwise healthy BHT users. Due to the lack of sufficient data to support the efficacy or safety of BHT, we recommend the use of United States Food and Drug Administration-approved regimens in the management of menopausal symptoms.

In the USA, over 30 million women are in or near menopause. Menopause is associated with a cluster of issues. Vasomotor symptoms (VMS) are the number one complaint of most menopausal women. VMS are disruptive to women during the day and at night, which leads to poor sleep, anxiety, depression and poor concentration. Up until now, the only US FDA-approved medication for moderate-to-severe VMS was hormone therapy. Hormone therapy may not be appropriate for all women. Many drugs are used off-label to treat VMS. The most often used agents are agents that are FDA-approved medications, such as selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors. The pharmaceutical company, Noven Pharmaceuticals (FL, USA), has studied paroxetine mesylate 7.5 mg, previously known as low-dose mesylate salt of paroxetine, specifically to treat moderate-to-severe VMS in postmenopausal women. Paroxetine is a selective serotonin reuptake inhibitor, and is thought to help decrease VMS by regulating body temperature via neurotransmitters. Paroxetine is approved to treat various psychiatric disorders, but is used at much higher doses (20-60 mg/day).

As health care providers, we must engage our female patients in a dialogue about their contraceptive and fertility decisions. Empowering and educating our patients about their bodies' hormones, the menstrual cycle, and the risk of unintended pregnancy are central to effective contraceptive counseling. Selecting an appropriate method for a patient and her medical profile is rewarding and challenging in view of new medications, novel delivery systems, and evolving research.

Many women are turning to bioidentical hormone therapy on the basis of misconceptions and unfounded claims, eg, that this therapy can reverse the aging process and that it is more natural and safe than approved hormone therapy. The aim of this article is to clarify some of the misconceptions.

Background: Vasomotor symptoms (VMS); (hot flushes and night sweats) are the most common menopausal complaint for which women seek treatment. Several therapies can be considered to help manage these complaints. The objective of this review is to assess the risks and benefits of available and emerging therapeutic options for the management of menopausal VMS., Methods: A review of the literature was conducted based on relevant publications identified through a PubMed search for clinical trials of agents used in the treatment of VMS., Results: Hormone therapy (HT) remains the most effective treatment available, but there will always remain a need for nonhormonal options. Evidence does not support the efficacy of alternative or over-the-counter products, such as phytoestrogens and black cohosh, and their long-term safety is largely unknown. There is evidence supporting the efficacy of selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) for the management of VMS from clinical trials of paroxetine, venlafaxine, and desvenlafaxine. Gabapentin appears to be effective, but the doses required may cause poor tolerability and reduced patient adherence. Data also suggest that clonidine has a modest effect at the expense of considerable adverse effects., Conclusions: Choosing an appropriate treatment approach for the management of VMS requires careful assessment of the riskbenefit ratio of each alternative, as well as individual patient preference.

Species and biotype distribution was determined in 44 bovine viral diarrhea virus- (BVDV-) positive samples submitted to the Animal Disease Diagnostic Laboratory (ADDL) in Indiana during 2006-2008. BVDV RNA was detected in the 5'-untranslated region and N(pro) region using reverse transcriptase PCR followed by sequencing analysis of the PCR product. Additionally, cases were classified into one of six categories according to history and/or lesions: acute symptomatic, hemorrhagic, respiratory distress, reproductive, persistent infection (PI), and mucosal disease (MD). Of 44 BVDV-positive samples, 33 were noncytopathic (ncp), 10 were cytopathic (cp), and one presented both ncp and cp biotypes. Sequencing analysis demonstrated that all samples belonged to BVDV-1a, BVDV-1b, or BVDV-2. The most common isolate was ncp BVDV-1b, (44%) followed by ncp BVDV-2a (24%). Among the six categories, respiratory clinical signs were the most common (36%) followed by PI (25%) and MD (16%).

After menopause, women become more susceptible to periodontal disease. We believe the problem is due in large part to estrogen deficiency with resulting bone loss and inflammatory processes. Osteoporosis and periodontal disease are best diagnosed early so that treatment can be started sooner and fractures and tooth loss can be prevented.

From September 2005 through October 2006, fibromatosis was diagnosed in 2 red squirrels (Tamiasciurus hudsonicus) and 1 gray squirrel (Sciurus carolinensis). All 3 squirrels had multifocal to coalescing, tan, firm alopecic cutaneous nodules. Two squirrels also had pulmonary nodules. Histologically, the cutaneous nodules had marked epidermal hyperplasia, with ballooning degeneration of keratinocytes, spongiosis, and eosinophilic cytoplasmic inclusions. The dermis was expanded by proliferation of atypical mesenchymal cells with cytoplasmic inclusions. Additional findings included pulmonary adenomatous hyperplasia with cytoplasmic inclusions, renal tubular epithelial hyperplasia with cytoplasmic inclusions, atypical mesenchymal proliferation in the liver, and atypical mesenchymal proliferation with cytoplasmic inclusions in the seminal vesicles. Ultrastructurally, poxviral particles were observed in skin scrapings and sections of cutaneous and pulmonary nodules. Polymerase chain reaction targeting the highly conserved Leporipoxvirus DNA polymerase gene was positive using DNA extracted from the cutaneous lesions of all 3 squirrels. Nucleotide sequence of the 390 base PCR amplicons was closely related to that of other members of the genus Leporipoxvirus. To the authors' knowledge, this is the first report of cutaneous and systemic poxviral disease in American red squirrels with molecular characterization of the squirrel fibroma virus.

Background: Osteopenia/low bone mineral density (BMD) can lead to osteoporosis and is far more prevalent than osteoporosis. The National Osteoporosis Foundation (NOF) has recommendations for prevention and treatment of low BMD; however, the condition remains underrecognized and undertreated. We assessed practice patterns between physician knowledge of low BMD and prescribing of additional pharmacological therapies as defined by the NOF guidelines., Methods: This is a retrospective, observational chart review of electronic medical records of 99 postmenopausal women aged > or =60 years with T-scores between -1.0 and -2.5 on baseline BMD done in 2003 at the Cleveland Clinic Women's Health Center. Counseling, advisement of weightbearing exercise, recommendation of calcium and vitamin D supplementation, and adequate pharmacological therapy in the form of bisphosphonates, hormone therapy, or selective estrogen receptor modulators (SERMs) were assessed. The management of bone specialists credentialed both by the International Society of Clinical Densitometry and the North American Menopause Society and non-bone specialists was also compared., Results: Bone specialists were more likely than non-bone specialists to offer counseling in the form of letters, phone encounters, and follow-up office visits and recommend weightbearing exercises. Most physicians recommended calcium and vitamin D supplementation regardless of specialty. There is no significant difference in the prescribing of pharmacological agents vs. conservative measures for osteopenic postmenopausal women by non-bone specialists vs. bone specialists as defined by the NOF guidelines, such that non-bone specialists did not treat these women any less aggressively than did bone specialists., Conclusions: Osteopenia is adequately managed in our institution regardless of physician group. However, non-bone specialists should consider more direct counseling about bone health and consider advisement of weightbearing exercise.

Bovine viral diarrhea (BVD) is one of the economically important diseases of cattle. For many years, different types of vaccines have been commercially available, yet this disease is hard to control in high-density population areas. Detection and isolation of bovine viral diarrhea virus (BVDV) from any potential reservoir is vital, especially when considering virus eradication from a herd or locale. One potential source is wild ruminants. Ear notches and lymph nodes were collected from the wild population of white-tailed deer (Odocoileus virginianus) during deer hunting season in Indiana and tested for BVDV with a commercial BVD antigen capture enzyme-linked immunosorbent assay. Two samples out of 745 collected samples were positive, and subsequently cp and ncp BVDV was isolated from 1 ear notch and 1 lymph node. These isolates were genotyped as type 1a and 1b based on sequence analysis of the 5' untranslated region (UTR). The results of the present study indicate that the prevalence of BVDV in the white-tailed deer population of Indiana is about 0.3%. Wild ruminants infected with BVDV should be taken into consideration during an eradication program of BVDV from the livestock population.

Mesial temporal lobe epilepsy (MTLE), the most common epilepsy in adults, is generally intractable and is suspected to be the result of recurrent excitation or inhibition circuitry. Recurrent excitation and the development of seizures have been associated with aberrant mossy fiber sprouting in the hippocampus. Of the animal models developed to investigate the pathogenesis of MTLE, post-status epilepticus models have received the greatest acceptance because they are characterized by a latency period, the development of spontaneous motor seizures, and a spectrum of lesions like those of MTLE. Among post-status epilepticus models, induction of systemic kainic acid or pilocarpine-induced epilepsy is less labor-intensive than electrical-stimulation models and these models mirror the clinicopathologic features of MTLE more closely than do kindling, tetanus toxin, hyperthermia, post-traumatic, and perinatal hypoxia/ischemia models. Unfortunately, spontaneous motor seizures do not develop in kindling or adult hyperthermia models and are not a consistent finding in tetanus toxin-induced or perinatal hypoxia/ischemia models. This review presents the mechanistic hypotheses for seizure induction, means of model induction, and associated pathology, especially as compared to MTLE patients. Animal models are valuable tools not only to study the pathogenesis of MTLE, but also to evaluate potential antiepileptogenic drugs.

Toxoplasmosis was diagnosed in a woodchuck (Marmota monax) and 2 American red squirrels (Tamiasciurus hudsonicus). The woodchuck was euthanized by a wildlife rescue organization in New York after progressive clinical signs of head tilt, circling, and rapid weight loss. Necropsy examination revealed acute subdural hemorrhage over the right cerebral hemisphere. Histologic lesions included meningoencephalitis, myocarditis, and hepatitis. Protozoal cysts were present in affected and unaffected neuroparenchyma. The squirrels were found dead, emaciated, and moderately infested with fleas near a park in northern Indiana. In both squirrels, the lungs were consolidated with numerous nodules up to 2 mm in diameter. Histologically, pneumonia and encephalitis were associated with intracellular and free protozoa. Additional histologic lesions included multifocal lymphoplasmacytic encephalitis with intralesional protozoa in both squirrels. The protozoa were positive with Toxoplasma gondii-specific immunohistochemistry and had ultrastructural features consistent with T. gondii in both squirrels. A real-time polymerase chain reaction test using T. gondii-specific probes demonstrated protozoal DNA in the lung, brain, and kidney of the squirrels and in the brain and heart of the woodchuck. To the authors' knowledge, this is the first report of toxoplasmosis in woodchucks or American red squirrels. Because rodents are common near urban settlements, this finding underscores their role as important intermediate hosts for T. gondii.

Our goal in this paper is twofold. First, it provides a brief overview of the macrotrends in women's health education over the last 25 years. Second, these trends are a backdrop for a discussion of women's health education as exemplified by a detailed review of the curriculum for the Women's Health fellowship at the Cleveland Clinic Foundation. We have termed the underpinning of the curriculum the "leadership triad" consisting of (1) clinical skills, (2) focused research, and (3) interdisciplinary education. These elements are presented in a detailed curriculum for a 2-year fellowship program. We see these elements as fundamental to the Cleveland Clinic's fellowship program, and a useful model for those contemplating or refining their advanced women's health curriculum.

Leiomyosarcoma was diagnosed in the uterus surgically removed from a 3-year-old pet Suffolk ewe with a history of bleeding from the vulva, spontaneous lactation, and nursing behavior. The uterus contained multiple well-circumscribed, soft, intraluminal polypoid masses of variable sizes (0.5-4 cm). The masses were red, with white, smooth, and glistening cut surfaces. Histologically they comprised variably dense sheets of moderately pleomorphic, plump spindle cells embedded in richly vascularized stroma. The mitotic index was usually low (0-1/high-power field), but in some polyps there were up to 10 mitoses/high-power field. Neoplastic cells stained positive for alpha smooth muscle actin (alpha-SMA) by immunohistochemistry. Ultrastructural features of neoplastic cells included the presence of basal lamina, scant microfilaments, contracted nuclei with blunt ends, and flat intercellular junctions. Uterine leiomyosarcoma was diagnosed based on cellular morphology and atypia and positive immunohistochemistry for alpha-SMA.

Hormonal therapy remains the gold standard for treating menopausal symptoms. In addition, some formulations are indicated for preventing and treating bone loss. In this article, we review some of the hormonal regimens that have been approved in the past 5 years.

Several newer hormonal contraceptive agents have become available in recent years. Many of them are slight variations on previous agents. In this article, we review the advantages, side effects, and practical considerations of hormonal contraceptives approved in the last few years.

The objective was to assess the effects of reminder letters on women returning for repeat bone density. We queried our clinical data repository to identify all women undergoing dual-energy X-ray absorptiometry (DXA) during the entire 2003 calendar year. Women with abnormal DXAs were entered into a database for reminder letters. The electronic medical record was then reviewed for the presence of the reminder letter and whether any repeat DXA scan was done. Approximately half of the women returned for repeat DXA of this group, approximately one-third were improved, one-third deteriorated, and the remaining were unchanged. We suggest a clinical benchmark of a minimum of 50% of women with abnormal bone density returning for repeat DXA on the same machine at a DXA imaging center should be a quality improvement goal. Further research into exploring why patients do not return for serial DXA and the impact of reminder letters on improving treatment outcomes should be conducted.

Objectives: To assess the effect of menopausal hormone therapy (HT) on reoccurrence, cancer-related mortality, and overall mortality after a diagnosis of breast cancer., Methods: We performed a quantitative review of all studies reporting experience with menopausal HT for symptomatic use after a diagnosis of breast cancer. Rates of reoccurrence, cancer-related mortality, and overall mortality were calculated in this entire group. A subgroup analysis was performed in studies using a control population to assess the odds ratio of cancer reoccurrence and mortality in hormone users versus non-users., Results: Fifteen studies encompassing 1416 breast cancer survivors using HT were identified. Seven studies included a control group comprised of 1998 patients. Among the 1416 HT users, reoccurrence was noted in 10.0% (95% CI: 8.4-11.6%). Cancer-related mortality occurred at a rate of 2.6% (95% CI: 1.8-3.7%), while overall mortality was 4.5% (95% CI: 3.4-5.8%). Compared to non-users, patients using HT had a decreased chance of reoccurrence and cancer-related mortality with combined odds ratio of 0.5 (95% CI: 0.2-0.7) and 0.3 (95% CI: 0.0-0.6), respectively., Conclusions: In our review, menopausal HT use in breast cancer survivors was not associated with increased cancer reoccurrence, cancer-related mortality or total mortality. Despite conflicting opinions on this issue, it is important for primary care physicians to feel comfortable medically managing the increasing number of breast cancer survivors. In the subset of women with severe menopausal symptoms, HT options should be reviewed if non-hormonal methods are ineffective. Future trials should focus on better ways to identify breast cancer survivors who may safely benefit from HT versus those who have a substantial risk of reoccurrence with HT use.