Sequential management of postmenopausal health and osteoporosis: An update.

Increased life expectancy means that women are now in a hypoestrogenic state for approximately one-third of their lives. Overall health and specifically bone health during this period evolves in accordance with aging and successive exposure to various risk factors. In this review, we provide a summary of the approaches to the sequential management of osteoporosis within an integrative model of care to offer physicians a useful tool to facilitate therapeutic decision-making. Current evidence suggests that pharmacologic agents should be selected based on the risk of fractures, which does not always correlate with age. Due to their effect on bone turnover and on other hormone-regulated phenomena, such as hot flushes or breast cancer risk, we position hormone therapy and selective estrogen receptor modulators as an early postmenopause intervention for the management of postmenopausal osteoporosis. When the use of these agents is not possible, compelling evidence supports antiresorptive agents as first-line treatment of postmenopausal osteoporosis in many clinical scenarios, with digestive conditions, kidney function, readiness for compliance, or patient preferences playing a role in choosing between bisphosphonates or denosumab during this period. For patients at high risk of osteoporotic fracture, the "anabolic first" approach reduces that risk. The effect on bone health with these bone-forming agents or with denosumab should be consolidated with the subsequent use of antiresorptive agents. Regardless of the strategy, follow-up and treatment should be maintained indefinitely to help prevent fractures.

Clinical perspectives on the menstrual pictogram for the assessment of heavy menstrual bleeding.

Heavy menstrual bleeding (HMB) has an estimated prevalence of 18-32% but is known to be under-reported due to poor recognition and estimation of menstrual blood loss (MBL). HMB can negatively impact quality of life, affecting social interactions, work productivity and sexual life. Abnormal menstrual bleeding may have an underlying structural or systemic cause, such as endometrial and myometrial disorders; however, for some, there is no identified pathological cause. Several methods are available for assessing MBL, including the alkaline hematin (AH) method and the menstrual pictogram (MP). The AH method is considered to be the most accurate way to monitor MBL; however, it is associated with inconvenience and expense, therefore limiting its value outside of research. The MP requires the user to select an icon from a chart that reflects the appearance of a used sanitary product; the icon is associated with a blood volume that can be used to determine MBL. Validation studies have demonstrated that the results of the MP and AH method are well correlated, showing that the MP can measure MBL with sufficient accuracy. Additionally, the MP is more convenient for users, less expensive than the AH method, may be used in regions where the AH method is unavailable and may also be used as part of a digital application. Overall, the MP offers a convenient approach to monitor MBL both in research and clinical practice settings.

Medical management of heavy menstrual bleeding: a comprehensive review of the literature.

IMPORTANCE: Heavy menstrual bleeding (HMB) is a common complaint among reproductive-aged women, which negatively affects their health as well as their social, professional, and family lives. Modern medical management usually provides effective control of HMB irrespective of the underlying cause. Surgical interventions should be reserved for women with significant pelvic pathology and those unresponsive to medical therapy. OBJECTIVE: The aim of this review was to provide a comprehensive summary of the efficacy and safety of available medical treatments of HMB. EVIDENCE ACQUISITION: A comprehensive MEDLINE and EMBASE literature search was undertaken using selected terms associated with HMB to identify clinical studies published before March 20, 2013, that reported changes in menstrual blood loss in women receiving medical intervention. RESULTS: The effectiveness of treatments to reduce HMB due to endometrial dysfunction in descending order was as follows: (1) the levonorgestrel-releasing intrauterine system (LNG-IUS) (initial release rate of 20 µg of LNG per 24 hours), (2) combined hormonal contraceptives (oral or transvaginal), (3) tranexamic acid, and (4) long-course oral progestogens (≥3 weeks per cycle). The LNG-IUS was found to reduce HMB due to some structural causes (leiomyomas and adenomyosis). The reduction in menstrual blood loss achieved with nonsteroidal anti-inflammatory drugs and short-course oral progestogens (≤14 days per cycle) is less impressive but may be sufficient for women who have marginally increased blood loss. CONCLUSIONS AND RELEVANCE: For women not seeking pregnancy, the LNG-IUS is the first-line medical therapy for HMB, with combined hormonal contraceptives as second choice. For other women, fewer effective options exist.

[Third generation selective estrogen receptor modulators: benefits beyond bone. II, endometrial action]. / Beneficio extraóseo de los moduladores selectivos del receptor estrogénico de tercera generación: II, acción en el endometrio.

The selective estrogen receptor modulators (SERMs) are substances with estrogenic/anti-estrogen effect that act differently depending on the tissue and composition. Since the discovery that tamoxifen and raloxifene (RLX) had a breast cancer preventive effect, the search for the perfect SERM has been the goal. The evidence that tamoxifen significantly increased the risk of endometrial cancer as compared to placebo made this tissue the center of interest in developing new SERMs. Thus, ospemifen, arzoxifene, lasofoxifene (LFX) and bazedoxifene (BZA) appeared as third-generation SERMs but only BZA reached the stage of clinical use. Both experimental and clinical data available on the effects of RLX or third-generation SERMs reaching clinical stage (LFX and BZA) show either neutrality or anti-estrogenic effects at endometrial level. BZA has shown to be equivalent to vehicle in several experimental conditions and acts as anti-estrogen in models were estrogens (conjugated equine estrogens [CEE] or E2) were co-administered. In a 7 years pivotal study the incidence of endometrial adenocarcinoma has been significantly lower in the BZA than in the placebo group. Moreover, in a clinical trial to evaluate the ability of a combination of BZA and CEE to prevent hot flushes in symptomatic postmenopausal women, doses of 20mg or higher of BZA have significantly decreased the risk of presenting endometrial hyperplasia when co-administered with either 0.650 or 0.450mg of CEE.

[Third generation selective estrogen receptor modulators benefits beyond bone: effects on breast]. / Beneficios extraóseos de los moduladores selectivos del receptor estrogénico de tercera generación: efectos sobre la mama.

The selective estrogen receptor modulators (SERMs) are substances with estrogenic/anti-estrogen effect that act differently depending on the tissue and composition. Since the discovery that tamoxifen and raloxifene (RLX) had a breast cancer preventive effect, the search for the perfect SERM has been the goal. Thus, ospemifen, arzoxifene, lasofoxifene and bazedoxifene (BZA) appeared as third-generation SERMs. Among all them, only BZA reached the stage of clinical use. BZA has been shown to have an anti-estrogen effect in experimental studies, but not a protective effect on clinical breast cancer in pivotal clinical trials (301 and extensions). However, in these studies comparing BZA versus RLX and placebo, RLX has not shown the expected preventive effect on breast cancer. This lack of effect can be the consequence of the size and characteristics of BZA's studies in a population with low incidence of breast cancer.