Sexual well-being after menopause: An International Menopause Society White Paper.

Sexual well-being frequently declines following the menopause transition and can be associated with significant personal and relationship distress. This distress is the hallmark of female sexual dysfunction (FSD). FSD is highly prevalent in postmenopausal women. The prevalence of sexual problems increases with age, but conversely this is associated with decreasing distress with advancing age. This pattern has been seen across multiple international populations with varied cultural norms. While the etiology of FSD is multifactorial, the physiological changes of sex hormone insufficiency and postmenopausal symptoms, such as dyspareunia, are primary factors contributing to FSD at midlife. The International Menopause Society is working to increase awareness of FSD and to provide a framework for practitioners to address sexual medicine concerns. This White Paper aims to review the process of care for female sexual well-being following menopause, from initially approaching the discussion of FSD, to identifying clinical signs and symptoms, and ultimately determining the best available biopsychosocial therapies. As with most processes of care, the first step is often the most difficult. Health-care practitioners need to broach the topic of sexuality in the clinical setting. Lack of information on, comfort with, and biases about the topic of sexuality after menopause are significant hurdles that the International Menopause Society addresses in this document. Each member of the Writing Group remains committed to continued advocacy for the validity of FSD as a diagnosis, the need for therapies for women to be both available and included in health insurance coverage, and continued therapeutic research to provide evidence-based solutions.

Temperature measurement in the microscopic regime: a comparison between fluorescence lifetime- and intensity-based methods.

Thermally sensitive fluorescent indicators have been proposed to monitor temperature changes in microfluidic systems, mainly based on fluorescence intensity or lifetime. However, measuring temperature in a structured environment, such as biological tissue, presents additional challenges due to the chemical and structural complexity. Here, we investigate the potential for resolving temperature distributions within the volume of a single cell. Rhodamine B (RhB) dye was employed as a temperature indicator to compare fluorescence intensity- and lifetime-based techniques. The relationship between the fluorescence lifetime and temperature was found to be highly dependent on the biological environment. The intensity-based method allowed the temperature distribution to be mapped with partial success within the volume of a single cell. Under ideal circumstances, the temperature can be mapped pixel by pixel with a resolution better than ±0.3°C within the cell cytoplasm, but this accuracy was reduced to ±1.8°C by environmental variations. These results suggest that the fluorophore should be encapsulated and immobilized in the biological tissue in order to reduce the influence of environmental factors on temperature measurements at the cellular level.

The polarized AB plot for the frequency-domain analysis and representation of fluorophore rotation and resonance energy homotransfer.

The graphical representation of single-frequency phase-modulation fluorescence lifetime imaging data, referred to as the AB plot, is extended to take into account measurements of the polarized components of the fluorescence. For a hindered rotator model (characterized with a single excited-state lifetime, a single rotational correlation time and limiting initial and final anisotropies) the rotational correlation time and the excited lifetime can be determined from the AB plot of any two of the following emission components: parallel, perpendicular, total emission or combinations thereof. A strategy for resolving the component hindered rotations and lifetimes for mixtures of two hindered rotators from measurements of the total, parallel and perpendicular components of the emission is developed. The analysis does not require prior knowledge of the initial limiting anisotropy or of the steady-state anisotropy or of the excited state lifetime. Plots in polarized AB space derived for heterogeneous systems are constructed to aid interpretation of frequency-domain dynamic depolarization imaging microscopy experiments. These plots can be used to distinguish spatially dependent rotational correlation time heterogeneity from heterogeneity in limiting anisotropies. The effects of noise and aperture depolarization are discussed. It is anticipated that the polarized AB plot will provide a useful adjunct to existing methods for visualizing and analysing dynamic polarization phenomena arising from molecular dynamics and homo-energy transfer in single-frequency microscopy applications.

Combination therapy in fibromyalgia.

Fibromyalgia is an enigmatic medical condition whose specific etiology remains undiscovered but currently plagues five million Americans. Research indicates that the origin of the disease is most likely multifactorial. Treatment should therefore be tailored accordingly. Thus, it is often necessary to combine different options in order to achieve the maximum benefit in patients suffering from fibromyalgia.

Oriented circular dichroism of a class A amphipathic helix in aligned phospholipid multilayers.

The effect of lipid phase state on the orientation and conformation of a class A alpha-helical peptide on aligned lipid multilayers was examined using oriented circular dichroism spectroscopy. A comparison of oriented spectra in aligned peptide-lipid multilayers with CD spectra of unaligned peptide lipid vesicle complexes is consistent with a preferential alignment of helices parallel to the membrane surface at temperatures above and below the main acyl-chain melting transition temperature of the phospholipid. Changes are observed in the oriented CD spectra with lipid phase state which are attributed to a subtle conformational change of the peptide on the lipid surface. The results are compared with available experimental data on membrane-active lytic and antimicrobial helical peptides.

Positron-emission tomography and personality disorders.

This study used positron-emission tomography to examine cerebral metabolic rates of glucose (CMRG) in 17 patients with DSM III-R diagnoses of personality disorder. Within the group of 17 personality disorder patients, there was a significant inverse correlation between a life history of aggressive impulse difficulties and regional CMRG in the frontal cortex of the transaxial plane approximately 40 mm above the canthomeatal line (CML) (r = -.56, p = 0.17). Diagnostic groups included antisocial (n = 6), borderline (n = 6), dependent (n = 2), and narcissistic (n = 3). Regional CMRG in the six antisocial patients and in the six borderline patients was compared to a control group of 43 subjects using an analysis of covariance with age and sex as covariates. In the borderline personality disorder group, there was a significant decrease in frontal cortex metabolism in the transaxial plane approximately 81 mm above the CML and a significant increase in the transaxial plane approximately 53 mm above the CML (F[1,45] = 8.65, p = .005; and F[1,45] = 7.68, p = .008, respectively.

Recognition and assessment of sexual dysfunction associated with depression.

Recognition of sexual dysfunction associated with depression or its treatment is critical for patient satisfaction and medication compliance. This report reviews relevant literature related to types of sexual problems, the etiology of sexual dysfunction, prevalence rates, barriers to assessment, and available instruments for evaluating sexual functioning in individuals with depression. Evaluation of sexual functioning should include examination of each phase of the sexual response cycle, with classification of sexual disorders as described in the DSM-IV. Sexual functioning requires both an adequate hormonal milieu and appropriate neurotransmitter functioning. Evaluation of sexual functioning should include a sexual history, current level of sexual functioning, history and current diagnoses of medical and psychiatric illnesses, evaluation of medications and/or other substances taken, indicated endocrine measures, and targeted physical examination. Appropriate evaluation of sexual functioning associated with depression could help reduce the enormous societal costs of this disorder.

Substitution of an SSRI with bupropion sustained release following SSRI-induced sexual dysfunction.

BACKGROUND: We examine changes in sexual functioning and depressive symptoms in patients' transition from a selective serotonin reuptake inhibitor (SSRI), which induced both a therapeutic response and sexual dysfunction, to bupropion sustained release (SR) over the course of an 8-week trial. METHOD: The study included 11 adults (8 women and 3 men) who had a DSM-IV diagnosis of major depressive disorder in remission (Hamilton Rating Scale for Depression [HAM-D] score < 11) and were receiving an SSRI. Depression (using the HAM-D) and sexual dysfunction (using the Changes in Sexual Functioning Questionnaire) were assessed at baseline, 2 weeks after bupropion SR was added to the current antidepressant (combined treatment), 2 weeks after taper of the SSRI was initiated and completed, and after 4 weeks of bupropion SR monotherapy. T tests were performed to assess changes in depression and sexual function. RESULTS: Patient participation dropped from the initial group of 11 at week 2 to 9 at week 4 and to 6 by week 8. Sexual functioning improved from week 0 (baseline) to week 2 and from week 2 to week 4. The patients showed no significant change in mean HAM-D scores in weekly comparisons during the study period; 55% of patients completed the substitution without significant adverse events or recurrence of depressive symptoms. CONCLUSION: Bupropion SR as a treatment for depression also alleviates sexual dysfunction due to SSRI treatment. Results show that sexual functioning improves after the addition of bupropion SR to SSRI treatment and continues to improve, after discontinuation of the SSRI, with bupropion SR treatment alone.

Patient satisfaction with psychiatric treatment of menopausal women in a multidisciplinary women's midlife center.

OBJECTIVE: Menopause may be associated with new onset psychiatric symptoms or may exacerbate or heighten preexisting psychiatric problems in women. We present a model center for midlife women, with a multidisciplinary approach to treating this population, and patients' perceptions of satisfaction with treatment received during referral visits to an outpatient psychiatry clinic. DESIGN: In this study, 59 patients were referred from their primary care provider at the midlife center for evaluation by a faculty psychiatrist in an outpatient setting. A brief telephone interview was administered within 1 year of initial evaluation, using items from the Client Satisfaction Questionnaire-8 (CSQ-8) to assess patient satisfaction with psychiatric services received during the referral visits. Findings were based on responses provided by 50 women who were successfully contacted by telephone for the follow-up assessment. RESULTS: For this sample, the mean total client satisfaction score was 27.8 (s = 5.4) of a possible score of 32, which indicated that most women who were referred for psychiatric services reported a positive experience with the services provided by outpatient psychiatrists and reported being very satisfied with their treatment. CONCLUSIONS: We feel that this model center represents a unique way to identify and treat psychiatric disorders in a patient population that may be at high risk for depression and other psychiatric disorders.

Spectral properties of fluorescein in solvent-water mixtures: applications as a probe of hydrogen bonding environments in biological systems.

Although fluorescein is a widely used fluorescent probe in the biosciences, the effect of solvent environment on its spectral properties is poorly understood. In this paper we explore the use of fluorescein as a probe of the state of hydrogen bonding in its local environment. This application is based on the observation, originally made by Martin (Chem. Phys. Lett. 35, 105-111, 1975), that the absorption maximum of fluorescein undergoes substantial shifts in organic solvents related to the hydrogen bonding power of the solvents. We have extended this work by studying the spectral properties of the dianion form of the probe in solvent-water mixtures. We show that the magnitude of the shift correlates with the alpha and beta parameters of Kamlet and Taft (J. Am. Chem. Soc. 98, 377-383; 2886-2894, 1976), which provide a scale of the hydrogen bond donor acidities and acceptor basicities, respectively, of the solvents. In solvent-water mixtures, these shifts reflect general effects of the solvents on the hydrogen bonding environment of the fluorescein through water-solvent hydrogen bonding and specific effects due to fluorescein-solvent hydrogen bonding. Indeed, both the absorption and fluorescence properties appear to be dominated by these effects indicating that the spectral shifts of the dianion can be used as an indicator of its hydrogen bonding environment. We discuss the application of fluorescein as a probe of hydrogen bonding in the microenvironment immediately surrounding the fluorophore, and we illustrate the effect with reference to the fluorescein-antifluorescein antibody complex where it appears that antibodies selected during the immune response possess binding sites that are increasingly dehydrated and hydrophobic.

Bienestar sexual después de la menopausia: documento técnico de la Sociedad Internacional de la Menopausia / Sexual well-being after menopause: document Technician of the International Menopause Society

El bienestar sexual frecuentemente disminuye después de la transición de la menopausia y puede asociarse con estrés personal y de la relación. Este estrés es la característica típica de la disfunción sexual femenina (DSF). La DSF es altamente prevalente en mujeres posmenopáusicas. La prevalencia de problemas sexuales aumenta con la edad, pero por otra parte, esto se asocia con una disminución del estrés con el avance de la edad. Este patrón se ha visto en múltiples poblaciones internacionales con variadas normas culturales. Si bien la etiología de la DSF es multifactorial, los cambios fisiológicos de la insuficiencia de las hormonas sexuales y los síntomas posmenopáusicos, como la dispareunia, son los principales factores que contribuyen a la DSF en la mediana edad. La Sociedad Internacional de Menopausia está trabajando para incrementar el conocimiento de la DSF y proporcionar un esquema para que los profesionales aborden las preocupaciones sobre medicina sexual. El presente documento técnico tiene como objetivo revisar el proceso de cuidado del bienestar sexual femenino después de la menopausia, desde un abordaje inicial de la discusión de DSF hasta identificar signos y síntomas clínicos y, en última instancia, determinar las mejores terapias biopsicosociales disponibles. Al igual que con la mayoría de los procesos de atención, el primer paso es a menudo el más difícil. Los profesionales de la salud necesitan abordar el tema de la sexualidad en el entorno clínico. La falta de información, comodidad al respecto, y los prejuicios sobre el tema de la sexualidad después de la menopausia son obstáculos importantes que la Sociedad Internacional de Menopausia aborda en este documento; cada miembro del grupo que lo escribe sigue comprometido con la defensa continua para la validación de la DSF como un diagnóstico, la necesidad de que las terapias para mujeres estén disponibles e incluidas en la cobertura del seguro de salud, y la investigación terapéutica continua para proporcionar soluciones basadas en la evidencia.

Flibanserin: a potential treatment for Hypoactive Sexual Desire Disorder in premenopausal women.

Hypoactive Sexual Desire Disorder (HSDD) is defined as a persistent or recurrent deficiency of sexual fantasies and desire for sexual activity, which causes marked personal distress or interpersonal difficulty, and is not better accounted for by another psychiatric disorder or the direct physiological effects of a substance (e.g., a medication) or medical condition. HSDD is believed to be the most common form of Female Sexual Dysfunction and is associated with emotional distress and relationship problems. No pharmacologic therapy is approved for the treatment of HSDD in premenopausal or naturally postmenopausal women. Flibanserin is a 5-HT(1A) agonist/5-HT(2A) antagonist that is under investigation as a treatment for HSDD in women. The aim of this article is to present an overview of the pharmacology, clinical efficacy and safety of flibanserin. Flibanserin is an investigational drug that is not licensed for any indication in any country.

Recruitment of adenomatous polyposis coli and beta-catenin to axin-puncta.

The adenomatous polyposis coli (APC) tumour suppressor is a multifunctional protein involved in the regulation of Wnt signalling and cytoskeletal dynamics. Little is known about how APC controls these disparate functions. In this study, we have used APC- and axin-fluorescent fusion proteins to examine the interactions between these proteins and show that the functionally distinct populations of APC are also spatially separate. Axin-RFP forms cytoplasmic punctate structures, similar to endogenous axin puncta. Axin-RFP recruits beta-catenin destruction complex proteins, including APC, beta-catenin, glycogen synthase kinase-3-beta (GSK3-beta) and casein kinase-1-alpha (CK1-alpha). Recruitment into axin-RFP puncta sequesters APC from clusters at cell extensions and this prevents its microtubule-associated functions. The interaction between APC-GFP and axin-RFP within the cytoplasmic puncta is direct and dramatically alters the dynamic properties of APC-GFP. However, recruitment of APC to axin puncta is not absolutely required for beta-catenin degradation. Instead, formation of axin puncta, mediated by the DIX domain, is required for beta-catenin degradation. An axinDeltaDIX mutant did not form puncta, but still mediated recruitment of destruction complex proteins and phosphorylation of beta-catenin. We conclude that there are distinct pools of APC and that the formation of axin puncta, rather than the axin/APC complex, is essential for beta-catenin destruction.

Exploratory study of premenstrual symptoms and serotonin variability.

Premenstrual symptoms can pose significant problems for a large number of women; this small exploratory study was designed to investigate biological markers that may provide etiological clues. Using an algorithm based on daily symptom charting for two months, 15 participants were assigned to one of three study groups: non-symptomatic (n = 9), probable PMS (n = 3) and probable PMDD (n = 3). During two overnight admissions, one prior to and one following the onset of menses, participants had blood drawn to assess the level of available serotonin via one of its metabolites, 5-HIAA. The three groups exhibited potentially significant differences in several biological markers. This study's results are consistent with a hypothesis implicating serotonin in the generation of premenstrual symptomology.

Conformation and orientation of penetratin in phospholipid membranes.

The binding, conformation and orientation of a hydrophilic vector peptide penetratin in lipid membranes and its state of self-association in solution were examined using circular dichroism (CD), analytical ultracentrifugation and fluorescence spectroscopy. In aqueous solution, penetratin exhibited a low helicity and sedimented as a monomer in the concentration range approximately 50-500 microM. The partitioning of penetratin into phospholipid vesicles was determined using tryptophan fluorescence anisotropy titrations. The apparent penetratin affinity for 20% phosphatidylserine/80% egg phosphatidylcholine vesicles was inversely related to the total peptide concentration implying repulsive peptide-peptide interactions on the lipid surface. The circular dichroism spectra of the peptide when bound to unaligned 20% phosphatidylserine/80% egg phosphatidylcholine vesicles and aligned hydrated phospholipid multilayers were attributed to the presence of both alpha-helical and beta-turn structures. The orientation of the secondary structural elements was determined using oriented circular dichroism spectroscopy. From the known circular dichroism tensor components of the alpha-helix, it can be concluded that the orientation of the helical structures is predominantly perpendicular to the membrane surface, while that of the beta-type carbonyls is parallel to the membrane surface. On the basis of our observations, we propose a novel model for penetratin translocation.

Sex differences in clinical presentation and response in panic disorder: pooled data from sertraline treatment studies.

OBJECTIVE: Gender differences in clinical presentation and response to sertraline treatment were examined for patients diagnosed with DSM-III-R panic disorder with or without agoraphobia. METHOD: Data was pooled from 4 double-blind, placebo-controlled outpatient studies (males, N = 335; females, N = 338). Two were 12-week fixed-dose studies (sertraline 50 mg vs. 100 mg vs. 200 mg) and 2 were 10-week flexible-dose studies (sertraline 50-200 mg). Primary outcome measures consisted of the Clinical Global Impression-Improvement scale (CGI-I) and change in panic attack frequency. RESULTS: The clinical presentation of panic disorder was similar except that men reported an earlier age of onset, shorter duration of illness, and significantly more frequent history of alcohol and/or substance dependence/abuse. Sertraline was significantly more effective than placebo in both women and men on the 2 primary outcome measures. When between-sex efficacy was compared, women achieved significantly greater improvement than men on panic frequency and CGI-I, but had equivalent improvement on all other measures. There was no significant between-sex difference in study completion rates, or in adverse event profiles. CONCLUSIONS: There was a modest but consistent trend for women to show superior efficacy at the end of acute sertraline treatment. This gender effect only occasionally achieved significance, and must be confirmed by future treatment research.