Role of androgens, progestins and tibolone in the treatment of menopausal symptoms: a review of the clinical evidence

Estrogen-containing hormone therapy (HT) is the most widely prescribed and well-established treatment for menopausal symptoms. High quality evidence confirms that estrogen effectively treats hot flushes, night sweats and vaginal dryness. Progestins are combined with estrogen to prevent endometrial hyperplasia and are sometimes used alone for hot flushes, but are less effective than estrogen for this purpose. Data are conflicting regarding the role of androgens for improving libido and well-being. The synthetic steroid tibolone is widely used in Europe and Australasia and effectively treats hot flushes and vaginal dryness. Tibolone may improve libido more effectively than estrogen containing HT in some women. We summarize the data from studies addressing the efficacy, benefits, and risks of androgens, progestins and tibolone in the treatment of menopausal symptoms

Reducing depression during the menopausal transition: Study protocol for a randomised controlled trial

Background: The menopausal transition (MT) is a biological inevitability for all ageing women that can be associated with changes in mood, including depressive symptoms. There is tentative evidence that women who develop depression during the MT have greater risk of subsequent depressive episodes, as well as increased health morbidity and mortality. Thus, preventing depression during the MT could enhance both current and the future health and well-being of women. This study aims to test the efficacy of a client-centred health promotion intervention to decrease the 12-month incidence of clinically significant symptoms of depression among women undergoing the MT.Methods/Design: This randomised controlled trial will recruit 300 women undergoing the MT living in the Perth metropolitan area. They will be free of clinically significant symptoms of depression and of psychotic or bipolar disorders. Consenting participants will be stratified for the presence of subsyndromal symptoms of depression and then randomly assigned to the intervention or control group. The intervention will consist of eight telephone health promotion sessions that will provide training in problem solving and education about the MT, healthy ageing, depression and anxiety, and management of chronic health symptoms and problems. The primary outcome of interest is the onset of a major depressive episode according the DSM-IV-TR criteria during the 12-month follow-up or of clinically significant symptoms of depression, as established by a score of 15 or greater on the Patient Health Questionnaire (PHQ-9). Secondary outcomes of interest include changes in the severity of symptoms of depression and anxiety (Hospital Anxiety and Depression Scale, HADS), quality of life (Short Form Health Survey, SF-12), and lifestyle.Discussion: Current evidence shows that depressive symptoms and disorders are leading causes of disability worldwide, and that they are relatively common during the MT. This study will use a multifaceted health promotion intervention with the aim of preventing depression in these women. If successful, the results of this trial will have implications for the management of women undergoing the MT. Trial registration: Australian and New Zealand Clinical Trials Registry ACTRN12613000724774. Date registered: 1 July 2013

The role of artistic creative activities in navigating the COVID-19 pandemic in Australia

During the COVID-19 pandemic some Australians turned to artistic creative activities (ACAs) as a way of managing their own mental health and well-being. This study examined the role of ACAs in regulating emotion and supporting mental health and well-being during the COVID-19 pandemic, and also attempted to identify at-risk populations. We proposed that (1) participants would use ACAs as avoidance-based emotion regulation strategies; and (2) music engagement would be used for emotion regulation. Australian participants (N = 653) recruited from the general public completed an online survey, which included scales targeting anxiety (GAD7 scale), depression (PHQ9 scale) and loneliness (two UCLA Loneliness Scales, referring to “Before” and “Since” COVID-19). Participants reported which ACAs they had undertaken and ceased during the pandemic using an established list and ranked their undertaken ACAs in terms of effectiveness at making them “feel better.” For their top-ranked ACA, participants then completed the Emotion Regulation Scale for Artistic Creative Activities (ERS-ACA), and if participants had undertaken any musical ACAs, also the Musical Engagement Questionnaire (MusEQ). The results supported both hypotheses. ANOVAs indicated that participants ranked significantly higher on the “avoidance” ERS-ACA subscale than the other subscales, and that participants ranked significantly higher on the emotion regulation and musical preference MusEQ subscales than the other subscales. Additionally, while ACAs such as “Watching films or TV shows” and “Cookery or baking” were common, they ranked poorly as effective methods of emotion regulation, whereas “Listening to music” was the second-most frequently undertaken ACA and also the most effective. “Singing” and “Dancing” were among the most ceased ACAs but also ranked among the most effective for emotion regulation, suggesting that support for developing pandemic-safe approaches to these ACAs may provide well-being benefits in future crises. Additionally, correlation analyses showed that younger participants, those who took less exercise during the pandemic, and those with the highest musical engagement reported the poorest well-being. We conclude that ACAs provided an important resource for supporting mental health and well-being during the COVID-19 pandemic in Australia and could potentially support mental health and well-being in future crises

Long-term progestin contraceptives (LTPOC) induce aberrant angiogenesis, oxidative stress and apoptosis in the guinea pig uterus: A model for abnormal uterine bleeding in humans

BACKGROUND: Irregular uterine bleeding is the major side effect of, and cause for, discontinuation of long-term progestin-only contraceptives (LTPOCs). The endometria of LTPOC-treated women display abnormally enlarged, fragile blood vessels (BV), decreased endometrial blood flow and oxidative stress. However, obtaining sufficient, good quality tissues have precluded elucidation of the mechanisms underlying these morphological and functional vascular changes. METHODS: The current study assessed the suitability of the guinea pig (GP) as a model for evaluating the uterine effects of LTPOC administration. Thus GPs were treated with a transdermal pellet for 21 days and examined for endometrial histology, angiogenic markers as well as markers of oxidative stress and apoptosis. RESULTS AND DISCUSSION: We now demonstrate that GP uteri were enlarged by both estradiol (E2) and medroxyprogesterone acetate (MPA) (p < 0.001). Effects of MPA on uterine weight differed significantly depending on E2 levels (p < 0.001), where MPA opposed the E2 effect in combined treatments. Angiogenesis parameters were similarly impacted upon: MPA alone increased BV density (p = 0.036) and BV average area (p = 0.002). The presence of E2 significantly decreased these parameters. These changes were associated with highly elevated of the lipid peroxidation product, 8-isoprostane (8-isoP) content in E2+MPA-treated and by nuclear 8-OH-deoxyguanosine (8oxoG) staining compared to all other groups (p < 0.001). Abnormalities in the E2+MPA group were consistent with chromatin redistribution, nuclear pyknosis, karyolysis and increased apoptosis as observed by a marked increase in TUNEL labeling. CONCLUSIONS: LTPOC exposure alters endometrial vascular and tissue morphology consistent with oxidative stress and apoptosis in a complex interplay with endogenous estrogens. These findings are remarkably similar to in vivo change observed in the human uterus following LTPOC administration. Hence, the GP is an excellent model for the study of LTPOC effects on the uterus and will be extremely useful in determining the mechanistic pathways involved in this process which cannot be conducted on humans

A longitudinal examination of perinatal testosterone, estradiol and vitamin D as predictors of handedness outcomes in childhood and adolescence

The developmental origins of handedness remain elusive, though very early emergence suggests individual differences manifesting in utero could play an important role. Prenatal testosterone and Vitamin D exposure are considered, yet findings and interpretations remain equivocal. We examined n = 767 offspring from a population-based pregnancy cohort (The Raine Study) for whom early biological data and childhood/adolescent handedness data were available. We tested whether 18-week maternal circulatory Vitamin D (25[OH]D), and testosterone and estradiol from umbilical cord blood sampled at birth predicted variance in direction of hand preference (right/left), along with right- and left-hand speed, and the strength and direction of relative hand skill as measured by a finger-tapping task completed at 10 (Y10) and/or 16 (Y16) years. Although higher concentrations of Vitamin D predicted more leftward and less lateralized (regardless of direction) relative hand skill profiles, taken as a whole, statistically significant findings typically did not replicate across time-point (Y10/Y16) or sex (male/female) and were rarely detected across different (bivariate/multivariate) levels of analysis. Considering the number of statistical tests and generally inconsistent findings, our results suggest that perinatal testosterone and estradiol contribute minimally, if at all, to subsequent variance in handedness. Vitamin D, however, may be of interest in future studies