Mucus concentration-dependent biophysical abnormalities unify submucosal gland and superficial airway dysfunction in cystic fibrosis.

Cystic fibrosis (CF) is characterized by abnormal transepithelial ion transport. However, a description of CF lung disease pathophysiology unifying superficial epithelial and submucosal gland (SMG) dysfunctions has remained elusive. We hypothesized that biophysical abnormalities associated with CF mucus hyperconcentration provide a unifying mechanism. Studies of the anion secretion-inhibited pig airway model of CF revealed elevated SMG mucus concentrations, osmotic pressures, and SMG mucus accumulation. Human airway studies revealed hyperconcentrated CF SMG mucus with raised osmotic pressures and cohesive forces predicted to limit SMG mucus secretion/release. Using proline-rich protein 4 (PRR4) as a biomarker of SMG secretion, CF sputum proteomics analyses revealed markedly lower PRR4 levels compared to healthy and bronchiectasis controls, consistent with a failure of CF SMGs to secrete mucus onto airway surfaces. Raised mucus osmotic/cohesive forces, reflecting mucus hyperconcentration, provide a unifying mechanism that describes disease-initiating mucus accumulation on airway surfaces and in SMGs of the CF lung.

Postmenopausal Hormone Therapy-Local and Systemic: A Pharmacologic Perspective.

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.

Managing Genitourinary Syndrome of Menopause in Breast Cancer Survivors Receiving Endocrine Therapy.

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 CO2 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.

Correction: Genitourinary syndrome of menopause.

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."

Genitourinary syndrome of menopause in breast cancer survivors:Treatments are available.

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.

ERAAs for menopause treatment: Welcome the 'designer estrogens'.

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.

Medical management of urinary incontinence in women.

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.

Buccal Bone Thickness in the Esthetic Zone of Postmenopausal Women: A CBCT Analysis.

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.

Update: A Review of Women's Health Fellowships, Their Role in Interdisciplinary Health Care, and the Need for Accreditation.

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.

Can the FRAX tool be a useful aid for clinicians in referring women for periodontal care?

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.

Risks and effectiveness of compounded bioidentical hormone therapy: a case series.

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.

Paroxetine: a first for selective serotonin reuptake inhibitors - a new use: approved for vasomotor symptoms in postmenopausal women.

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).

A need to educate postmenopausal women of their periodontal health.

BACKGROUND: Postmenopausal women have shown proactive willingness to take responsibility for their changing health care needs. The example of osteoporosis is a model that when educated of their bone health status, this cohort follows through with prevention and treatment regimens. Postmenopausal status is considered to be a risk factor for periodontitis. It is known that up to 50% of periodontal disease goes undiagnosed. The goal of periodontal therapy is to prevent tooth loss. OBJECTIVE: Is there a need, then to educate and inform postmenopausal women of their periodontal status? Can dentists provide a greater service to this cohort by increasing education and information? MATERIALS AND METHODS: The current study compares patient perception to actual clinical findings in 94 postmenopausal women. Patients are informed of their diagnosis, and educated about the disease, its risk factors and preventive and treatment modalities. Detailed interviews examine the patient intentions to follow up on preventive and treatment regimens suggested. RESULTS: Although 97.8% of participants reported having "healthy gums", 36.2% had severe periodontitis in at least one site. Interviews reveal that patients associated disease with abscess, and would be likely to follow prevetive and treatment regimens when they were informed of their diagnosis and educated on the topic. CONCLUSION: The findings suggest a need to make education a priority when treatment postmenopausal women.

Update on contraceptive options: a case-based discussion.

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.

Bioidentical hormone therapy: clarifying the misconceptions.

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.

Assessing risks and benefits of nonhormonal treatments for vasomotor symptoms in perimenopausal and postmenopausal women.

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.

Is long-term bisphosphonate therapy associated with benefits to the periodontium in postmenopausal women?

OBJECTIVE: The aim of this study was to compare the periodontium of postmenopausal women with known low bone mineral density who are receiving long-term bisphosphonate therapy with those who are not. METHODS: The periodontal status of 28 white postmenopausal women with low bone density using bisphosphonate therapy for at least 2 years was compared with that of a matching group not using such therapy. All women underwent a cone-beam CT scan of the jaw and a complete periodontal examination evaluating for plaque score, periodontal probing depth, clinical attachment loss, bleeding on probing, and alveolar bone height. RESULTS: Bisphosphonate users had higher plaque score, lower probing depth, and lesser clinical attachment loss compared with the controls. These differences were determined to be significant by both t test and Wilcoxon's tests. Bleeding on probing was lower and the alveolar bone height was higher in the bisphosphonate group than in controls, but these differences were not statistically significant. Linear models showed no significant interactions between plaque score and bisphosphonate use, suggesting that the association of periodontal status and outcome measures was constant across all levels of plaque scores. Bisphosphonate use was a significant factor for probing depth but was not significant for the other parameters when adjusted for plaque score. CONCLUSIONS: Long-term bisphosphonate use seems to have some beneficial effects on the periodontium of postmenopausal women with low bone density, across all levels of plaque score.