Non-estrogen-based treatments for menopausal symptoms

The British Menopause Society Council is committed to provide up-to-date authoritative reviews to aid health professionals to inform and advise women about key issues in postreproductive health. This guidance refers to non-estrogen-based treatments for menopausal symptoms, such as hot flushes, symptoms of urogenital atrophy and lack of sexual desire. Treatment of choice should be based on up to-date information and targeted to individual women's needs. Non-hormonal strategies may be useful for women with estrogen-dependent disease such as breast cancer.     

The future of the new selective estrogen receptor modulators

Selective estrogen receptor modulators (SERMs) are compounds that display mixed estrogen agonist/antagonist activity. Currently, four SERMs are licensed for clinical use: tamoxifen, toremifene, clomifene and raloxifene. The STAR and RUTH trials have provided useful data about the potential role of SERMs in the primary prevention of breast cancer and cardiovascular disease in postmenopausal women. New-generation SERMs, such as bazedoxifene, arzoxifene, lasofoxifene and ospemifene, are currently being evaluated. The aim is to find a SERM that conserves the skeleton and prevents breast cancer without increasing the risk of endometrial cancer and venous thromboembolism, and without inducing hot flushes. Technological advances in the study of estrogen receptor activation will provide key information for drug development.     

Qualitative inquiry into women's menopause experiences in southeastern Iran

Menopause is defined as amenorrhea for one year. Signs and symptoms are categorized as physical and psychological changes, including depression, hot flushes and ageing. Woman's responses to menopause are governed by lifestyle factors. The purpose of this study was to determine how Iranian women experience menopause and hormone therapy. A qualitative inquiry was conducted through semistructured, in-depth interviews to explore study questions in 11 menopausal women. Participants had positive and negative menopause experiences. Negative menopause experiences are due to severity of symptoms. Menopause can be facilitated by increasing women's knowledge about this phase and ways to cope with it.     

Treatment of postmenopausal vaginal atrophy with 10-μg estradiol vaginal tablets

Postmenopausal estrogen deficiency can lead to symptoms of urogenital atrophy. Individuals with urogenital atrophy have symptoms that include vaginal dryness, vaginal and vulval irritation, vaginal soreness, pain and burning during urination (dysuria), increased vaginal discharge, vaginal odour, vaginal infections, recurrent urinary tract infections, pain associated with sexual activity (dyspareunia) and vaginal bleeding associated with sexual activity. Despite the frequency and effects of vaginal atrophy symptoms, they are often under-reported and, consequently, under-treated. Therefore, care of a menopausal woman should include a physical assessment of vaginal atrophy and a dialogue between the physician and the patient that explores existing symptoms and their effect on vulvovaginal health, sexuality and quality-of-life issues. The development of the ultra-low-dose 10-μg estradiol vaginal tablets is in line with the requirements of regulatory agencies and women's health societies regarding the use of the lowest effective hormonal dose. Because of its effectiveness and safety profiles, in addition to its minimal systemic absorption, the 10-μg estradiol vaginal tablet can offer greater reassurance to health-care providers and postmenopausal women with an annual estradiol administration of only 1.14 mg.     

Bazedoxifene: a new selective estrogen receptor modulator for postmenopausal osteoporosis

An ongoing need for safe and effective pharmacological therapies exists for postmenopausal osteoporosis, which imposes a significant burden on both women and the health-care system. Bazedoxifene is a novel selective estrogen receptor modulator with a unique tissue-selectivity profile. In phase 3 clinical trials of nearly 10,000 postmenopausal women, bazedoxifene was shown to significantly reduce the risk of new vertebral fracture versus placebo, with favourable effects on bone mineral density, bone turnover markers and the lipid profile. Moreover, in a subgroup of women at increased risk of fracture, bazedoxifene significantly decreased non-vertebral fracture risk versus both placebo and raloxifene. Bazedoxifene has been shown to be safe and well tolerated, with no evidence of endometrial or breast stimulation. These data suggest that bazedoxifene may offer significant clinical benefit for postmenopausal women with or at risk of developing osteoporosis, which may subsequently lessen the medical and economic burden of this disease.     

Menopause and sexual desire: the role of testosterone

The present short review underlines the role of testosterone (T) in the motivational and satisfaction components of women's sexuality and critically discusses the strategies to treat hypoactive sexual desire disorder (HSDD), a condition of low desire associated with personal and/or interpersonal difficulties, which is more common in surgical menopausal women. There are multiple ways androgens target the brain regions (hypothalamic, limbic and cortical) involved in sexual function and behaviour. Even though circulating available androgens have been implicated in several domains of sexual response, they seem to be related weakly to symptoms, such as low sexual desire, poor sexual arousal, orgasm and diminished well-being in postmenopausal women. The possibilities of treating low sexual desire/HSDD are multifaceted and should include the combination of pharmacological treatments able to maximize biological signals driving the sexual response, and individualized psychosocial therapies in order to overcome personal and relational difficulties. Transdermal T has been shown to be effective at a dose of 300 μg/day both in surgically and naturally menopausal women replaced with estrogen or not, without any relevant side-effects. However, the decision to treat postmenopausal women with HSDD with T is mainly based on clinical judgement, after informed consent regarding the unknown long-term risks.     

National Osteoporosis Society's Position statement on hormone replacement therapy in the prevention and treatment of osteoporosis

Hormone replacement therapy (HRT) has been shown to increase bone density, reduce the risk of fracture and can successfully relieve menopausal symptoms. From a time when HRT was the major therapeutic option for the management of osteoporosis, women and their clinicians now have a range of treatments available. Following the publication of the Women's Health Initiative (WHI) and the Million Women Study highlighting potential side-effects, such as breast cancer, heart disease and stroke, many doctors and women are now reluctant to use HRT. The National Osteoporosis Society felt that the role of HRT in the management of osteoporosis needed to be clarified. Using the Charity's expert clinical and scientific advisers, and through public consultation with members and key stakeholders, a Position Statement has been published. We conclude that HRT has a role to play in the management of osteoporosis in postmenopausal women below the age of 60 years. The key recommendations of the Position Statement are presented in this paper.     

Systemic lupus erythematosus and hormone replacement therapy

The indications for hormone replacement therapy (HRT) in postmenopausal women is the treatment of climacteric symptoms and the prevention of osteoporosis. Women with systemic lupus erythematosus (SLE) are more likely to have a premature menopause, osteoporosis and cardiovascular disease. HRT can induce SLE flares and cardiovascular or venous thromboembolic events. Therefore it should not be used in women with active disease or those with antiphospholipid (aPL) antibodies. In general, it should be used only for patients without active disease, a history of thrombosis or aPL antibodies. Non-oral administration of estrogen is recommended because of its lesser effect on coagulation. With regard to the progestogen, progesterone or pregnane derivatives are preferred. Otherwise, non-estrogen-based strategies should be used.     

The use of selective estrogen receptor modulators on bone health in men

Selective estrogen receptor modulators (SERMs) represent a class of drugs that act as agonist or antagonist for estrogen receptor in a tissue-specific manner. The SERMs drugs are initially used for the prevention and treatment of osteoporosis in postmenopausal women. Bone health in prostate cancer patients has become a significant concern, whereby patients undergo androgen deprivation therapy is often associated with deleterious effects on bone. Previous preclinical and epidemiological findings showed that estrogens play a dominant role in improving bone health as compared to testosterone in men. Therefore, this evidence-based review aims to assess the available evidence derived from animal and human studies on the effects of SERMs on the male skeletal system. The effects of SERMs on bone mineral density (BMD)/content (BMC), bone histomorphometry, bone turnover, bone strength and fracture risk have been summarized in this review.     

Primary prevention of coronary heart disease in women

The British Menopause Society Council is committed to provide up-to-date authoritative reviews to aid health professionals to inform and advise women about key issues in postreproductive health. Coronary heart disease (CHD) is a leading cause of death in women. Observational studies have consistently shown estrogen to help prevent CHD in postmenopausal women. The large randomized controlled Women's Health Initiative (WHI) trial did not confirm these observational findings. However, further analyses of the WHI study as well as the observational Nurses' Health Study have now found that the timing of onset of hormone replacement therapy (HRT) use is important and that estrogen may have a protective role in CHD in women aged 50-59 years. This consensus statement will examine the evidence regarding HRT and non-estrogen therapies (lipid lowering agents, aspirin, antihypertensives, antidiabetic medications, selective estrogen receptor modulators [SERMs]) as well as diet, lifestyle and smoking cessation in the primary prevention of CHD in women.     

Mental health around and after the menopause

The menopause is a time in a woman's life when it is recognized that biological and social changes can impact upon mental wellbeing. Several studies have investigated the relationship between menopause and psychological symptoms, especially depression, with mixed results. In part, this is due to a considerable overlap between depressive symptoms and those due to declining estrogen levels, causing challenges in assessment. However it appears that vulnerable women are at a higher risk of succumbing to depression during menopausal transition. Antidepressants remain the mainstay of treating depressive symptoms, with little conclusive evidence for hormone replacement therapy. Memory problems during menopause are a common complaint, but there is no demonstrated link to subsequent dementia. This paper also reviews considerations of diagnosis and treatment of postmenopausal depression.     

Calcium and vitamin D--for whom and when

The basis of 'nutritional' interventions for the prevention of postmenopausal osteoporosis and osteoporotic fracture is a large topic with much genetic and biochemical evidence, as well as the results of randomized controlled trials, to guide the investigator and clinician. The efficacy of treatment with calcium and vitamin D was once controversial, but with the advent of controlled clinical trials using bone mineral density as an endpoint it has become clear that calcium with or without vitamin D therapy can lead to reductions in the rate of bone loss in postmenopausal women of all ages. Furthermore, with certain caveats, calcium with vitamin D therapy in the older postmenopausal woman can lead to useful reductions in fracture rates and falls, especially in populations with reduced exposure to sunlight, which is potentially the majority of postmenopausal women in both developed and developing countries. However, estrogen, selective estrogen receptor modulators (SERMs) and bisphosphonates (especially when given in combination with calcium and vitamin D) are more efficacious in preventing fracture, particularly in postmenopausal patients with impaired bone structure.     

Depression during menopausal transition: a review of treatment strategies and pathophysiological correlates

It has long been recognized that women are at a higher risk than men to develop depression and that such risk is particularly associated with reproductive cycle events. Recent long-term, prospective studies have demonstrated that the transition to menopause is associated with higher risk for new onset and recurrent depression. A number of biological and environmental factors are independent predictors for depression in this population, including the presence of hot flushes, sleep disturbance, history of severe premenstrual syndrome or postpartum blues, ethnicity, history of stressful life events, past history of depression, body mass index, socioeconomic status and the use of hormones and antidepressants. Accumulated evidence suggests that ovarian hormones modulate serotonin and noradrenaline neurotransmission, a process that may be associated with underlying pathophysiological processes involved in the emergence of depressive symptoms during periods of hormonal fluctuation in biologically predisposed subpopulations. Transdermal estradiol and serotonergic and noradrenergic antidepressants are efficacious in the treatment of depression and vasomotor symptoms in symptomatic, midlife women. The identification of individuals whom might be at a higher risk for depression during menopausal transition could guide preventive strategies for this population.     

Urogenital atrophy

The British Menopause Society Council aims to aid health professionals to inform and advise women about postreproductive health. This guidance refers to the long-term condition of urogenital atrophy. Treatment choice should be based on up to date information and targeted to individual women's needs. Non-estrogen and estrogen-based treatments are discussed.     

Estrogen treatment affects brain functioning after menopause

Sex hormones have powerful neuromodulatory effects on functional brain organization and cognitive functioning. This paper reviews findings from studies investigating the influence of sex hormones in postmenopausal women with and without hormone therapy (HT). Functional brain organization was investigated using different behavioural tasks in postmenopausal women using either estrogen therapy or combined estrogen plus gestagen therapy and age- and IQ-matched postmenopausal women not taking HT. The results revealed HT-related modulations in specific aspects of functional brain organization including functional cerebral asymmetries and interhemispheric interaction. In contrast to younger women during the menstrual cycle, however, it seems that HT, and especially estrogen therapy, after menopause affects intrahemispheric processing rather than interhemispheric interaction. This might be explained by a faster and more pronounced age-related decline in intrahemispheric relative to interhemispheric functioning, which might be associated with higher sensitivity to HT. Taken together, the findings suggest that the female brain retains its plasticity even after reproductive age and remains susceptible to the effects of sex hormones throughout the lifetime, which might help to discover new clinical approaches in the hormonal treatment of neurological and psychiatric disorders.     

The microanatomy of trabecular bone in young normal and osteoporotic elderly males

Normally there is a gradual continual loss of cortical and trabecular bone in both men and women as they age. Osteopenia and osteoporosis are conditions in which the loss results in brittle bones that fracture easily. Males with low testosterone and hypogonadism are predisposed to osteoporosis and prevention tends to be overshadowed by the greater problem in postmenopausal women. The ability of the skeleton to resist external forces depends partly upon the amount of bone present and partly upon other factors including cancellous bone microarchitecture. This is examined in iliac crest bone biopsies from idiopathic osteoporotic men, mean age 60 ± 12 SD years [n = 16]. These were compared with a healthy control group (autopsy samples), mean age 30 ± 8.9 years [n = 28] with the aim of examining the pattern of cancellous atrophy in male idiopathic osteoporosis. Undecalcified specimens were embedded in methylmethacrylate and prepared for histomorphometry. Sections were analysed using an automated trabecular analysis system (TAS), whereby a binary image was created. Area measurements including the trabecular surface and distance measurements including the trabecular width were made. The binary image was thinned to its medial framework and the node and terminus number as indices of trabecular interconnection were recorded, together with the strut length. Results (median (range)) showed a lower percentage bone volume in the elderly osteoporotic male, 10.2% (5.4–23.1) compared to young normals 25.2% (14.6–43.9), p < 0.001. The trabeculae tended to be thinner, 95.7 µm (66.7–170.7) c.f. 120.8 µm (75.8–208.6) and considerably fewer in number, 11.1 (2.1–31.4) c.f. 48.3 (25.4–66.9), p < 0.001 per field and in particular the number of nodes, 2.1 (0.15–14) c.f. 40.6 (10.3–74.1) per field and the node: terminus ratio fell to 0.13 (0.01–1.19) c.f. controls 0.98 (0.24–6.69), p < 0.001. It was concluded that the pattern of cancellous atrophy in male idiopathic osteoporosis differs from normal aging and resembles that in postmenopausal women. Results using the automated TAS confirm previous observations made manually.     

Dehydroepiandrosterone (DHEA) and the menopause: an update

Since we last reviewed this topic in 2001, considerably more information about dehydroepiandrosterone (DHEA) has accrued, but this has not necessarily left us any wiser about the use of this steroid in postmenopausal women. There is no further evidence that DHEA supplementation is likely to be useful in the prevention of cardiovascular disease or cognitive impairment, or in the promotion of wellbeing. Evidence has, however, accumulated for beneficial effects of DHEA on osteoporosis, both in postmenopausal women and in patients receiving long-term glucocorticoid therapy. What is also emerging is a link between low DHEA levels and cardiovascular risk, and between high DHEA levels and breast cancer risk. In fact, the benefits and adverse effects of DHEA administration in postmenopausal women increasingly resemble those of conventional hormone replacement therapy. Overall, we conclude that DHEA is not currently to be recommended for therapeutic use in the majority of postmenopausal women. However, DHEA supplementation may be of benefit in two specific groups of women: those with the lowest circulating levels of DHEA; and those for whom osteoporosis is a particular problem.     

Skin ageing

Cutaneous ageing manifests itself as a progressive reduction in maximum function and reserve capacity of skin tissue. It is not a unique and uniform biological event. Skin comprises three layers: epidermis, dermis and subcutaneous tissue. Collagen atrophy is a major factor in skin ageing. There is a strong correlation between skin collagen loss and estrogen deficiency due to the menopause. Skin ageing, especially in the face, is associated with a progressive increase in extensibility and a reduction in elasticity. With increasing age, the skin also becomes more fragile and susceptible to trauma, leading to more lacerations and bruising. Furthermore, wound healing is impaired in older women. Estrogen use after the menopause increases collagen content, dermal thickness and elasticity, and it decreases the likelihood of senile dry skin. Large-scale clinical trials are necessary to help make informed recommendations regarding postmenopausal estrogen use and its role in the prevention of skin ageing.     

Not Such Strange Bedfellows After All

Abstract

The irritable bowel syndrome (IBS) is best defined as abdominal pain of greater than three months duration, with or without a change in bowel habits. Barium studies, sedimentation rate, and the lactose tolerance test are usually within normal limits. The underlying physiology includes a predominance of 3 cycles/minute basal electrical rhythm (BER). The abdominal pain is poorly localized and usually intermittent, without a clear relationship to medication. Differential diagnosis should include inflammatory bowel disease, infectious colitis or gastroenteritis, lactose intolerance, gallbladder disease, peptic ulcer disease, pelvic inflammatory disease, ovarian cysts and tumors, and endometriosis. A sedimentation rate is an important part of the diagnostic workup which may or may not include barium studies. Anticholinergics have been shown to alter the abnormal BER of irritable bowel syndrome and have proven to be of use in treating this syndrome. Dietary counseling should include advising the patient to eat slowly and at regular hours, and heat applied to the abdomen in the form of a hot water bag has been useful. “Overprogrammed” individuals with irritable bowel syndrome should be advised to modify their activities as this type of stress may give rise to the symptoms.

“Effect of Estrogen/Progestin Potency on Lipid/Lipoprotein Cholesterol,” PATRICIA WAHL, CAROLYN WALDEN, ROBERT KNOPP, JOANNE HOOVER, ROBERT WALLACE, GERARDO HEISS, and BASH RIFKIND. We studied 374 women taking oral contraceptives, 284 women taking estrogen preparations after menopause, and 1086 women taking no hormones, to determine the relation of plasma lipids and lipoprotein cholesterol concentrations to various types of estrogen/progestin formulations. Premenopausal women using oral contraceptives containing a relatively low dose of estrogen combined with a medium or high dose of progestin (Norlestrin, Ovral, or Demulen) had a 24 per cent higher median concentration of low-density-lipoprotein cholesterol than did those not using hormones (P < 0.05). Women using oral contraceptives that are high in estrogen and low in progestin (Envoid or Oracon) had significantly higher concentrations of high-density-lipoprotein cholesterol than did nonusers; those using Ovral, a low-estrogen and high-progestin formulation, had significantly lower levels of high-density-lipoprotein cholesterol. In postmenopausal women the use of estrogen was associated with concentrations of low-density-lipoprotein cholesterol that were 11 to 19 per cent below the levels in postmenopausal women who did not use hormones. The effects of estrogen-progestin balance on low-density and high-density lipoproteins may underlie the increased incidence of stroke and myocardial infarction in women of childbearing age who take oral contraceptives. (New England Journal of Medicine 1983;308:862–7.)     

Methadone and Menopause: Midlife Women in Drug Treatment

ABSTRACT

As a rising number of midlife women receive methadone treatment, issues related to the menopausal transition take on increased importance. The similarity between many of the symptoms associated with opiate withdrawal, methadone and menopause (hot and cold flashes, sweats, fatigue, decreased libido, menstrual irregularity and insomnia), make it plausible these women and clinical staff attribute menopausal symptoms to other conditions of greater familiarity. The paucity of research, multiplicity of health problems and typically poor access to health care, further complicate the picture and underscore the importance of better integration of health care and social work intervention.