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

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

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

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

Quantification of Women Who Could Benefit from Hormone Therapy after Endometrial Cancer Treatment: An Analysis of SEER Data

Our primary aim was to estimate the magnitude of stage I endometrial cancer (EC) survivors that could benefit from hormonal therapy (HT). Our secondary aims were to assess EC incidence in women below 50 and below 60 over the years, and analyze the overall survival and any influencing factors. We analyzed the endometrioid EC data from the Surveillance, Epidemiology, and End Results (SEER) program according to women’s age, tumor stage, and grade. We analyzed the proportions of EC survivors below 50 and below 60 years of age and stratified those age groups by race. For age distribution and survival analysis SEER, 18 registries’ research data (2000–2018) were analyzed. We analyzed the SEER 12 registries’ research data (1992–2019) for incidence time trends. Our investigation found a 14% and 40% cumulative prevalence of stage I EC that occurs in women below 50 or 60 years, respectively. EC’s prevalence has progressively risen in recent decades, but cancer-specific mortality remains low. The increasing number of women affected by EC in premenopause or early postmenopause face an 18 years-survival rate of 96.86% and 95.73%, respectively. A significant proportion of low-grade EC survivors can potentially benefit from HT treatment, and this requires awareness of other aspects of their health or quality of life, in addition to cancer treatments