Best practice & research. Clinical endocrinology & metabolism最新文献

Defining, diagnosing and managing premenstrual disorders (PMDs) remains a challenge both for general practitioners and specialists. Yet these disorders are common and can have an enormous impact on women. PMDD (premenstrual dysphoric disorder), one severe form of PMD, has a functional impact similar to major depression yet remains under-recognised and poorly treated. The aim of this chapter is to give some clarity to this area, provide a framework for non-specialists to work towards, and to stress the importance of MDT care for severe PMDs, including PMDD.

Purpose

To summarise the dosing options, regimens, pharmacokinetics, risks and benefits of oestrogen-based therapies for the treatment of menopausal symptoms.

Methods

A review of the literature was undertaken using multiple databases. Randomised trials, observational studies, meta-analyses and review papers were included.

Results

Multiple systemic preparations of oestrogen exist and all appear comparable in terms of efficacy. They differ by pharmacokinetics and those preparations that avoid hepatic metabolism have a lower risk profile in general although their use can be limited by skin barriers or patient acceptability. All vaginal oestrogen treatments are comparable in efficacy and have not been associated with any health risks. Side-effects between all preparations differ.

Conclusions

With regards to oestrogen treatments there is not a one size fits all. Multiple treatments are available and a clinician’s role is to guide and help women make evidence based, unbiased and informed choices.

A continuous process of bone turnover is central to bone health and strength. If bone resorption exceeds bone formation, bone strength deteriorates with resultant fractures. Osteoporosis is defined by a fracture or bone mineral density. The lack of ovarian estrogen after menopause causes a significant loss in bone strength, placing women at higher risk of osteoporosis. The probability of future fractures can be calculated by identifying risk factors in all menopausal women. Preventive action starts with a bone-friendly lifestyle. The need for and type of interventive medication can best be determined by classifying fracture risk as low, high, or very high using a combination of fracture history, bone mineral density, 10-year fracture probability or country-specific values. As osteoporosis is an incurable disease, treatment should be seen as a lifelong strategy consisting of the correct sequencing of available bone-specific drugs and appropriate drug-free periods when applicable.

Androgens play a key biological role in libido and sexual arousal in women, and knowledge about their complex role in other systems remains ambiguous and incomplete. This narrative review examines the role of endogenous androgens in women’s health throughout the life span before focusing on evidence surrounding the use of androgen-based therapies to treat postmenopausal women. The role of testosterone as a therapeutic agent in women continues to attract controversy as approved preparations are rare, and use of off-label and compounded formulations is widespread. Despite this androgen therapy has been used for decades in oral, injectable, and transdermal formulations. Responses to androgen therapy have been demonstrated to improve aspects of female sexual dysfunction, notably hypoactive sexual desire disorder, in a dose related manner. Substantial research has also been conducted into the role of androgens in treating aspects of the genitourinary syndrome of menopause (GSM). Evidence for benefits beyond these is mixed and more research is required regarding long-term safety. However, It remains biologically plausible that androgens will be effective in treating hypoestrogenic symptoms related to menopause, either through direct physiological effects or following aromatization to estradiol throughout the body.

Women may experience changes in sexuality across menopause, because at this step in life hormone deficiency interacts with several determinants in a bio-psycho-social perspective. Healthcare providers should inform women about menopause impact on sexuality and be proactive during consultation in disclosing sexual concerns that would require a targeted assessment. Sexual symptoms become more frequent as women age, but they do not always translate into sexual dysfunction diagnosis, for which distress is required. It is important to recognize conditions that may increase the risk of dysfunctional response to menopause challenges in order to promote sexual longevity through counselling and specific management. In this review, we report key elements for a comprehensive assessment of sexual health around menopause, with a focus on genitourinary syndrome of menopause (GSM) and hypoactive sexual desire disorder (HSDD), representing well identified clinical conditions affecting sexuality at midlife and beyond. We also address the issue of contraception across the menopausal transition, highlighting risks and benefits, and possible implications on sexual function.

Menopausal women with an intact uterus choosing estrogens for menopausal symptom relief require a progestogen for endometrial protection. The aim of this systematic review was to evaluate the risks of endometrial hyperplasia resp. malignancy with different progestogens used in combined MHT. Overall, 84 RCTs were included. We found that 1) most studies were done with NETA, followed by MPA, MP and DYD and LNG, 2) most progestogens were only available as oral formulations, 3) the most frequently studied progestogens (oral MP, DYD, MPA, oral and transdermal NETA, transdermal LNG) were assessed in continuously as well as in sequentially combined MHT regimens, 4) FDA endometrial safety criteria were only fulfilled for some progestogen formulations, 5) most studies demonstrated endometrial protection for the progestogen dose and time period examined. However, 6) study quality varied which should be taken into account, when choosing a combined MHT, especially if off-label-use is chosen.

Primary hyperparathyroidism (PHPT), the most common cause of hypercalcemia, is most often identified in postmenopausal women with hypercalcemia and parathyroid hormone (PTH) levels that are either frankly elevated or inappropriately normal. The clinical presentation of PHPT includes three phenotypes: target organ involvement of the renal and skeletal systems; mild asymptomatic hypercalcemia; and more recently, high PTH levels in the context of persistently normal albumin-corrected and ionized serum calcium values. The factors that determine which of these three clinical presentations is more likely to predominate in a given country include the extent to which biochemical screening is employed, the prevalence of vitamin D deficiency, and whether a medical center or practitioner tends to routinely measure PTH levels in the evaluation of low bone density or frank osteoporosis. When biochemical screening is common, asymptomatic primary hyperparathyroidism is the most likely form of the disease. In countries where vitamin D deficiency is prevalent and biochemical screening is not a feature of the health care system, symptomatic disease with skeletal abnormalities is likely to predominate. Finally, when PTH levels are part of the evaluation for low bone mass, the normocalcemic variant is seen. Guidelines for surgical removal of hyperfunctioning parathyroid tissue apply to all three clinical forms of the disease. If guidelines for surgery are not met, parathyroidectomy can also be an appropriate option if there are no medical contraindications to surgery. In settings where either the serum calcium or bone mineral density is of concern, and surgery is not an option, pharmacological approaches are available and effective. Referencing in this article the most current published articles, we review the different presentations of PHPT, with particular emphasis on recent advances in our understanding of target organ involvement and management.

The gut microbiome has been implicated in a variety of neuropathologies with recent data suggesting direct effects of the microbiome on host metabolism, hormonal regulation, and pathophysiology. Studies have shown that gut bacteria impact host growth, partially mediated through the growth hormone (GH)/insulin-like growth factor 1 (IGF-1) axis. However, no study to date has examined the specific role of GH on the fecal microbiome (FMB) or the changes in this relationship following a traumatic brain injury (TBI). Current literature has demonstrated that TBI can lead to either temporary or sustained abnormal GH secretion (aGHS). More recent literature has suggested that gut dysbiosis may contribute to aGHS leading to long-term sequelae now known as brain injury associated fatigue and cognition (BIAFAC). The aGHS observed in some TBI patients presents with a symptom complex including profound fatigue and cognitive dysfunction that improves significantly with exogenous recombinant human GH treatment. Notably, GH treatment is not curative as fatigue and cognitive decline typically recur upon treatment cessation, indicating the need for additional studies to address the underlying mechanistic cause.

Preserving bone health is an important goal of care of patients with acromegaly and growth hormone deficiency (GHD). Both disorders are associated with compromised bone health and an increased risk of fracture. However, parameters of bone health that are routinely used to predict fractures in other populations, such as aBMD measured by DXA, are unreliable for this in acromegaly and GHD. Additional methodologies need to be employed to assess bone health in these patients. This review summarizes available data on the effects of acromegaly and GHD on parameters of bone health such as aBMD, volumetric bone mineral density (vBMD) and microarchitecture assessed by HRpQCT and other techniques, trabecular bone score (TBS) and fracture assessment. More research is needed to identify reliable predictors of fracture risk and to determine how best to screen for and treat those patients at risk so that bone health is optimized in these patients.