The Controversial History of Hormone Replacement Therapy

The history of hormone replacement therapy (HRT) started in the 1960s, with very high popularity in the 1990s. The first clinical trials on HRT and chronic postmenopausal conditions were started in the USA in the late 1990s. After the announcement of the first results of the Women's Health Initiative (WHI) in 2002, which showed that HRT had more detrimental than beneficial effects, HRT use dropped. The negative results of the study received wide publicity, creating panic among some users and new guidance for doctors on prescribing HRT. The clear message from the media was that HRT had more risks than benefits for all women. In the following years, a reanalysis of the WHI trial was performed, and new studies showed that the use of HRT in younger women or in early postmenopausal women had a beneficial effect on the cardiovascular system, reducing coronary disease and all-cause mortality. Notwithstanding this, the public opinion on HRT has not changed yet, leading to important negative consequences for women's health and quality of life

New needs for menopausal women during covid-19 pandemic. A physician-based investigation

It was evaluated whether the COVID-19 pandemic may have influenced the manifestation of menopausal symptoms. In a web interview, 143 physicians, experts on the menopause, were asked to rate their perceived prevalence of hot flush, sleep disorder, sexual disturbance, anxiety and depression as ‘rare’, ‘seldom’, ‘frequent’ and ‘very frequent’ in patients they managed prior to and during the COVID-19 pandemic. According to physicians, there was no major change in the prevalence of hot flush, sleep disorder and sexual disturbance but prevalence of anxiety (39-8% vs 75.5%; p < 0.0001) and depressive (35.6% vs 72.0%; p < 0.0001) symptoms increased during COVID-19 pandemic. COVID-19 pandemic has changed the composite picture of menopausal symptoms, challenging physicians to adjust their therapeutic approach to the new need. Approaches capable to treat vasomotor symptoms but also highly effective on mood disturbance should be preferred

Ospemifene in the management of vulvar and vaginal atrophy: Focus on the assessment of patient acceptability and ease of use

Endocrinological changes that occur with menopause lead to a chronic and progressive condition named vulvar and vaginal atrophy (VVA). This disease is characterized by symptoms such as dryness, dyspareunia, itching, burning, and dysuria. According to recent epidemiological studies, VVA has a high prevalence and can also occur in younger women prior to the menopause, negatively affecting quality of life, sexual function, intimacy and relationship with the partner. Accordingly, therapy should be effective, initiated early and continued for as long as possible. Up to recent years, available therapeutic options have included over-the-counter lubricants and moisturizers, vaginal oestrogens and systemic hormones. These products are not indicated for all women. Hormones are mostly contraindicated in women with a history of hormone-sensitive cancer and are frequently not accepted even by women without contraindications. Local therapies are frequently considered uncomfortable, difficult to apply, and messy. Indeed, these treatments have a high spontaneous discontinuation rate, mostly due to dissatisfaction, safety concern, side effects and difficulty in vaginal placement. Recently, ospemifene, a new non-hormonal systemic remedy, was approved by FDA (Food and Drug Administration) and EMA (European Medicines Agency) for the treatment of the two most bothersome symptoms of VVA: dryness and dyspareunia. Because ospemifene is a selective estrogen receptor modulator (SERM), it can be administered also in women with a history of breast cancer, and this makes it more acceptable by any woman. In addition, its route of administration minimizes those bothersome side effects intrinsic to the vaginal route of administration. Available data indicate that women using ospemifene have higher adherence to treatment, higher persistence and lower discontinuation rate. Satisfaction is higher than with other local therapies and overall health care cost is lower

Effect of deer density on tick infestation of rodents and the hazard of tick-borne encephalitis. II: Population and infection models

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Relation of Birthweight and Ovarian and Uterine Size Prior to Menarche

During pregnancy, supply of nutrients and exposure of the mother to environmental factors can influence fetus phenotype, possibly modifying growth of fetal tissues and organs. Few studies inconsistently reported that fetuses exposed to an insufficient energy supply, as those born small for gestational age, may have a reduced volume of uterus and ovaries. A retrospective analysis was performed on ultrasound data performed between 2012 and 2018 in 69 young premenarchal girls, 5 to 9\ua0years of age, attending our endocrine\u2013gynecologic clinic for a suspect of early puberty. Length of pregnancy and birthweight was also retrieved. When corrected for age, and presence of ovarian follicles, ovarian volume was positively (R2 = 0.210; p = 0.001) related to percentiles of birthweight (beta coefficient 0.012; 95% CI, 0.002\u20130.021). Similarly, uterine volume was positively (R2 = 0.237; p = 0.005) related to percentiles of birthweight (beta coefficient 0.067; 95% CI, 0.021\u20130.114). Ovarian (p = 0.034) and uterine (p = 0.014) volume was higher in the upper 3rd distribution of birthweight percentiles. In conclusion, development of ovarian and uterine volume increases progressively with the increase of birthweight percentiles. The data indicate an association between birthweight and the volume of uterus and ovary at 5\u20139\ua0years of age

Bridging human mobility to animal activity: when humans are away, bears will play

In the Anthropocene, findings on animal behavioral flexibility in response to anthropogenic changes are accumulating: human presence and activity affect the distribution, movement, activity rhythm, physiology, and diet of animal species. However, conclusions are limited by the lack of simultaneous quantitative data on both the animal and human side. Hence, the dynamic link between animal behavior and human activity and mobility is often poorly estimated. Based on long-term monitoring of a wild bear population in the Trentino region (10 bears monitored from 2006 to 2019; 20 bear-years) combined with human mobility data (Cumulative Outdoor activity Index, derived from the Strava Global Heatmap) and tourist count records, we investigated how spatial behavior and activity rhythms of bears change with variations in experienced human disturbance. We found that bears were mainly nocturnal and that, on an annual scale, nocturnality was associated with movement behavior, but both were independent of experienced human disturbance. Furthermore, nocturnality tended to increase in periods of more intense exploitation of outdoor areas by humans. Overall, these preliminary findings show that bears exhibit a notable behavioral flexibility to minimize their exposure to human presence. Through the application of different sources of human activity data, this work showcases that the integration of high resolution animal movement data with dynamic data on human mobility is crucial to meaningfully catch wildlife responses to anthropisation

Brown bear multi-scale response to human presence and mobility in the Italian Alps

In an increasingly human-dominated world, wildlife is constrained by human presence and activity, inducing behavioural adjustments as a consequence. Large mammals are especially sensitive to such changes, questioning the potential of their behavioural flexibility to cope with human disturbance. Using brown bears in the Italian Alps as a study case, we investigated their response to changes in human presence over different temporal scales. Combining human mobility data with bear tracking and activity data spanning from 2006 to 2019, we analysed bears’ behaviour and movement as a function of human activities. We observed that over the years bear activity and daily movement length have increased, while diurnality and range size have decreased. While tourism has grown in parallel, this was not identified as the main driver of such responses. Rather, it was mostly due to the increase in bear population, whose space is nonetheless limited by human infrastructure. At a weekly scale, we observed no difference in daily movement lengths between weekdays and weekends. This might perhaps be because of the continuous human disturbance in the area overall. Finally, at the daily scale, we found that individuals roamed in places more intensively exploited by humans at night compared to daytime, especially when ranging in heavily disturbed areas. Our results highlight how humans are indirectly, by hampering connectivity, and directly, through disturbance, shaping brown bear behaviour and movement. In view of a growing volume of outdoor human activity, we analyze the implications of such responses and present challenges for human-wildlife coexistence

Human infrastructure can alter the ecosystem services provided by a migratory ungulate

Wild ungulates, through their movement over the landscape, provide key ecosystem functions. Environmental processes such as soil productivity, seed dispersal and carbon sequestration are significantly affected by the presence of large herbivores. However, with the loss of migratory routes due to expanding human infrastructure networks and climate change, landscapes that depend on the movement of these species may experience changes in ecosystem functionality. Nutrient translocation and deposition, which is an important service provided by large herbivores, is of particular interest in alpine agricultural landscapes. Human activities generally have a negative impact on the quality, quantity, and dynamics of soil nutrient in the landscape, particularly nitrogen. Wild ungulates, with their movement and space use, can offset some of these human impacts by restoring concentrations over the landscape. In this project, we aim to map the nitrogen (N) flow derived by large migrating ungulates in a fragmented Alpine ecosystem. To this end, we developed an Agent-Based Model to quantify animal-vectored subsidies balance, based on observed movement of 15 GPS-tracked red deer over two years, and parameterized with population parameters from local monitoring, and species-specific information from literature. Preliminary stoichiometric nutrient budget maps indicate that human infrastructure networks and land use are shaping the movement of red deer, resulting in hotspots of nitrogen intake and uptake. Barrier to movements, caused by anthropogenic land use, has the potential to alter ecosystem services provided by free-ranging animals, particularly important in an ever-changing Alpine environment

Vasomotor symptoms and management of women undergoing treatment for breast cancer: literature review with focus on the therapeutic potential of cytoplasmic pollen extract

Objective: Effective management of vasomotor symptoms (VMS) in patients undergoing treatment for breast cancer (BC) represents a critical but frequent unmet need. This review summarizes the epidemiology, pathophysiology, and clinical features of VMS in patients with BC and provides a synopsis of the complementary and alternative medicine (CAM) approaches in relieving VMS with a focus on purified cytoplasm of pollen (PCP). Methods: The literature on VMS epidemiology, pathophysiology, clinical burden, and CAM treatment in healthy women and patients with BC was reviewed. Results: VMS are common in patients with BC undergoing hormonal treatment and negatively impact quality of life, leading to treatment discontinuation in up to 25% of patients with detrimental impact on risk of BC recurrence and overall survival. CAM approaches to treat VMS in patients with BC include vitamin E, phytoestrogens, and black cohosh, even if there is a lack of solid evidence to guide clinicians in the choice of treatment. PCP, obtained according to standards of good manufacturing practice, has a definite pharmacological mechanism of action, is devoid of estrogen activity, and has shown clinical efficacy on menopause-associated symptoms with a favorable safety profile and high compliance. As such, it appears to represent a valid management option to improve quality of life in patients with pre- and postmenopausal BC. Conclusions: Physicians should actively investigate the presence and impact of VMS in patients receiving therapy for BC. Additional and appropriately sized randomized clinical trials are needed to provide clear evidence on how to best meet the needs of patients with BC suffering from menopause-associated symptoms