Treatment of premenstrual disorders by suppression of ovulation by transdermal estrogens

The understanding of the cause and treatment of premenstrual disorders is confused but it is essentially the result of cyclical ovarian activity, usually ovulation, and an effective treatment should be by suppressing ovulation. This can be done by an oral contraceptive but as these women are progestogen intolerant the symptoms may persist becoming constant rather than cyclical. Alternatively, transdermal estradiol by patch, gel or implant effectively removes the cyclical hormonal changes, which produce the cyclical symptoms. A shortened seven-day course of a progestogen is required each month for endometrial protection but it can reproduce premenstrual syndrome-type symptoms in these women. Gonadotropin-releasing hormone with 'add-back' is effective in the short term. Laparoscopic hysterectomy and bilateral oophorectomy with adequate replacement of estrogen and testosterone should be considered in the severe cases with progestogenic side-effects.     

Pathophysiology of premenstrual syndrome and premenstrual dysphoric disorder

Premenstrual syndrome (PMS) and premenstrual dysphoric disorder are triggered by hormonal events ensuing after ovulation. The symptoms can begin in the early, mid or late luteal phase and are not associated with defined concentrations of any specific gonadal or non-gonadal hormone. Although evidence for a hormonal abnormality has not been established, the symptoms of the premenstrual disorders are related to the production of progesterone by the ovary. The two best-studied and relevant neurotransmitter systems implicated in the genesis of the symptoms are the GABArgic and the serotonergic systems. Metabolites of progesterone formed by the corpus luteum of the ovary and in the brain bind to a neurosteroid-binding site on the membrane of the gamma-aminobutyric acid (GABA) receptor, changing its configuration, rendering it resistant to further activation and finally decreasing central GABA-mediated inhibition. By a similar mechanism, the progestogens in some hormonal contraceptives are also thought to adversely affect the GABAergic system. The lowering of serotonin can give rise to PMS-like symptoms and serotonergic functioning seems to be deficient by some methods of estimating serotonergic activity in the brain; agents that augment serotonin are efficacious and are as effective even if administered only in the luteal phase. However, similar to the affective disorders, PMS is ultimately not likely to be related to the dysregulation of individual neurotransmitters. Brain imaging studies have begun to shed light on the complex brain circuitry underlying affect and behaviour and may help to explicate the intricate neurophysiological foundation of the syndrome.     

PMS and PMDD in the domain of mental health nursing

Premenstrual syndrome (PMS) is a complex cluster of symptoms that occurs 7 to 14 days prior to menses and ends 1 to 2 days after menses. Premenstrual syndrome symptoms can create severe, debilitating psychological and physical problems. The Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) provides criteria for premenstrual dysphoric disorder (PMDD), which can be considered the most severe presentation on the PMS continuum. A critical part of determining the diagnosis is evaluating the timing of symptoms. True PMS only occurs during the luteal phase of the menstrual cycle, with a symptom-free period during the follicular phase. After identifying a diagnosis of PMS or PMDD, the first-line treatment of these symptom clusters continues to be lifestyle changes, including stress management, healthy diet, regular aerobic exercise, cognitive-behavioral therapy, and fortified coping strategies. Women whose symptoms are not controlled adequately with lifestyle modifications may benefit from medications. Possible medication recommendations include selective serotonin re-uptake inhibitors (SSRIs), diuretics, gonadotropin-releasing hormone (GnRH) agonists, and vitamin and mineral supplements.     

Severe premenstrual syndrome and bipolar disorder: a tragic confusion

Bipolar disorder and severe premenstrual syndrome (PMS) have many symptoms in common, but it is important to establish the correct diagnosis between a severe psychiatric disorder and an endocrine disorder appropriately treatable with hormones. The measurement of hormone levels is not helpful in making this distinction, as they are all premenopausal women with normal follicle-stimulating hormone and estradiol levels. The diagnosis of PMS should come from the history relating the occurrence of cyclical mood and behaviour changes with menstruation, the improvement during pregnancy, postnatal depression and the presence of runs of many good days a month and the somatic symptoms of mastalgia, bloating and headaches. Young women with severe PMS do not respond to the antidepressants and mood-stabilizing drugs typically used for bipolar disorder.     

Gonadotrophin receptor hormone analogues in combination with add-back therapy: an update

Gonadotrophin receptor hormone analogues (GnRHa) have been used in a range of sex hormone-dependent disorders. In the management of premenstrual syndrome, they can completely abolish symptoms. The success of GnRHa in the treatment of endometriosis and adjuvant therapy in the management of fibroids is proven. This efficacy does not come without a cost and the side-effects of the hypo-estrogenic state have limited their application. The use of add-back therapy to counter these effects has enabled wider application, longer durations of treatment and an increase in compliance. This review article is an update on the evidence supporting gonadotrophin receptor hormone analogues in combination with add-back therapy.     

Classification of premenstrual disorders as proposed by the International Society for Premenstrual Disorders

Premenstrual disorders have been recognized as affecting innumerable women for decades but unlike most other medical conditions universally accepted criteria for definition and diagnosis are not established. Although premenstrual syndrome (PMS) occurs throughout reproductive life, there are some women who become particularly troubled. Those approaching the menopause may also have a mixture of PMS and menopause symptoms, not to mention heavy periods. Furthermore, some of the symptoms are similar in nature and so it is a challenge to identify which set of symptoms belongs to which spectrum. This is an area that has not been explored well. Various classifications have been proposed over the last few decades. A further effort towards the classification was made by an international multidisciplinary group of experts established as the International Society for Premenstrual Disorders (ISPMD) in Montreal in September 2008. Their deliberations resulted in a unified diagnosis, classification of premenstrual disorders (PMD) along with their quantification and guidelines on clinical trial design. This classification of PMS is far more comprehensive and inclusive than previous attempts. PMD in the ISPMD Montreal consensus are divided into two categories: Core and Variant PMD. Core PMD are typical, pure or reference disorders associated with spontaneous ovulatory menstrual cycles while Variant PMD exist where more complex features are present. Further, the consensus group considered that PMD may be subdivided into three subgroups predominantly physical, predominantly psychological and mixed. Variant PMD encompass primarily four different types; premenstrual exacerbation, PMD with anovulatory ovarian activity, PMD with absent menstruation and progestogen-induced PMD.     

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.     

Psychotropic medications and other non-hormonal treatments for premenstrual disorders

Selective serotonin re-uptake inhibitors have well-established efficacy for severe premenstrual syndrome and premenstrual dysphoric disorder. Efficacy has been reported with both continuous dosing (all cycle) and intermittent or luteal phase dosing (from ovulation to menses). Efficacy may be less with intermittent dosing, particularly for premenstrual physical symptoms. The efficacy of symptom-onset dosing (medication taken only on luteal days when symptoms occur) needs further systematic study. Women going through the menopausal transition may need to adjust their antidepressant dosing regimen due to the change in frequency of menstruation. Anxiolytics, calcium, chasteberry and cognitive-behaviour therapy may also have a role in the treatment of premenstrual symptoms.     

Insulin resistance and management of the menopause: a clinical hypothesis in practice

Insulin resistance (IR) is associated with a number of metabolic abnormalities including glucose intolerance, dyslipidemia and central obesity (the metabolic syndrome), which predispose to cardiovascular disease, diabetes mellitus and some cancers. The incidence of many of these conditions increases after the menopause, a time when IR also increases. Medical intervention to help alleviate menopausal symptoms, frequently vasomotor in origin, usually involves hormone replacement therapy (HRT), but some women may only experience partial symptom relief. We have hypothesized that this may be due to concurrent IR. Our approach is therefore to manage menopausal symptoms in conjunction with the treatment of any concurrent IR, achieved through a combination of hormone replacement, dietary intervention and, if necessary, an insulin sensitizer. We suggest that this approach may not only improve symptom relief but may also reduce the risk of developing more serious health complaints in the future.     

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.     

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.     

Compounded or confused? Bioidentical hormones and menopausal health

The aim of this article is to focus on compounded bioidentical hormone (BH) formulations for menopausal symptoms and to discuss the impact of these on women's choice of treatment. The practice of compounding BHs for individualized treatment of women with menopausal symptoms has developed in the USA. In spite of claims of superiority, there is no evidence to suggest that these formulations are any more efficacious or safe than conventional hormone replacement therapy (HRT). In fact, there are some concerns about dosing inconsistencies and usefulness of saliva testing that is carried out as part of this type of treatment. While there should be no serious safety issues for women, there is a mismatch between the reality of compounded BH formulations and women's perception of them.     

Epidemiology of premenstrual symptoms and disorders

The aim of this paper is to review published literature on the types and prevalences of premenstrual disorders and symptoms, and effects of these on activities of daily life and other parameters of burden of illness. The method involved review of the pertinent published literature. Premenstrual disorders vary in prevalence according to the definition or categorization. The most severe disorder being premenstrual dysphoric disorder (PMDD) affects 3-8% of women of reproductive age. This disorder focuses on psychological symptoms whereas global studies show that the most prevalent premenstrual symptoms are physical. Both psychological and physical symptoms affect women's activities of daily life. A considerable burden of illness has been shown to be associated with moderate to severe premenstrual disorders. In conclusion, premenstrual symptoms are a frequent source of concern to women during their reproductive lives and moderate to severe symptoms impact on their quality of lives.     

Web-based survey 'Contraception and attitudes to sexual behaviour' completed by women accessing a UK menopause website

Background and methodology Sociodemographic trends mean increasing numbers of new relationships in later life. These trends may not only have health consequences for women and health services but also impact on the targeting of sexual health messages. This study aimed to examine attitudes and knowledge surrounding contraception, sexual health and unwanted pregnancy among those accessing the website www.menopausematters.co.uk. A voluntary online survey was completed. RESULTS: Survey was completed by 550 respondents. Three hundred and sixty-six women, 94% of whom self-classified as pre- or perimenopausal, had been sexually active with a male partner in the previous four weeks. Commonest contraceptive methods used by perimenopausal and postmenopausal women were condoms, combined oral contraceptive pill (COCP) and male sterilization. Up to 42% of women surveyed were unhappy with their contraception. A total of 27% premenopausal, 32% perimenopausal women and 40% postmenopausal used no contraception. One-third of women were unhappy about this and 19 unplanned pregnancies had occurred. The majority of women were informed regarding COCP use over 35 years, hormone replacement therapy, emergency contraception and ceasing contraception. The majority of women were unaware that more terminations of pregnancy are performed in women over 40 than any other age group per total pregnancies.Almost a third of women were unaware that chlamydia incidence is increasing in older women. Most would use condoms in new relationship. Discussion and conclusions Women accessing www.menopausematters.co.uk are well informed about contraception and sexual health. The majority of those accessing the site are sexually active, but many use no contraception, or are unhappy with their chosen method, leaving them vulnerable to unwanted pregnancy or sexually transmitted infection.     

Harnessing hormonal signaling for cardioprotection

Cardiovascular disease is the leading cause of death in women in the Western world and is predominant among the elderly. A large body of evidence suggests that hormonal signaling plays a critical role in the regulation of cardioprotective mechanisms, as premenopausal women are at significantly lower risk of heart disease compared with men, but the risk greatly increases with the onset of menopause. This association indicates that estrogen may protect the heart from cardiovascular disease. Whereas a number of analyses of the effects of hormone replacement therapy (HRT) on postmenopausal women supported the idea that estrogen is a cardioprotective factor, the findings of the more recent Women's Health Initiative (WHI) study suggested that HRT may actually increase the risk of cardiovascular events. These conflicting reports have left both patients and clinicians reluctant to continue using current HRT regimes. The WHI findings do not, however, negate the epidemiological link between menopause and increased cardiovascular risk. Hence, the identification of the specific actions of estrogen that promote cardioprotective pathways without enhancing deleterious vascular mechanisms may provide novel estrogen-based alternatives to current HRT strategies. In this Review, we outline the known actions of estrogen on the cardiovascular system, focusing on cardioprotective mechanisms that may be targeted for the development of new therapeutic approaches.     

Homocysteine, menopause and cardiovascular disease

A high plasma concentration of total homocysteine (tHcy) and a deficiency of vitamins related to its metabolism, such as vitamin B12 and folate, have been associated with cardiovascular disease. Postmenopausal women have higher concentrations than age-matched premenopausal women, and plasma concentrations of homocysteine in postmenopausal women taking hormone replacement therapy are significantly lower than they are in those who do not take estrogen supplements. Because of the possible mixed effects of HRT on cardiovascular events, surrogate end-points must be evaluated with caution. While measuring homocysteine levels is relatively simple, evidence from well designed trials is awaited before population screening can be advocated. Also, the benefits of reducing homocysteine levels with folic acid and vitamin B6 and B12 supplements are highly debated.     

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.     

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.     

Treatment of lower urinary tract symptoms/benign prostatic hyperplasia and erectile dysfunction

Abstract

This article summarizes years of challenging research on erectile dysfunction (ED), a condition that has an important social and cultural relevance. Preclinical and clinical research progress has led to new therapeutic approaches to ED in patients with different comorbidities and particularly in those with low urinary tract symptoms (LUTS)/benign prostatic hyperplasia (BPH). These goals were possible only by combined work of specialists and researchers of different and intertwined medical disciplines. Currently, tadalafil (5?mg/d) is the best choice; other phosphodiesterase-5 inhibitors (PDE5i) are not included among options, despite the growing evidence of therapeutic effects. Different regimens of tadalafil may be prescribed based on patient needs, severity of LUTS/BPH – ED profile, and clinical experience. An integrated approach is necessary to choose for a combined therapy with PDE5i and α-blockers following urological and cardiac counseling in terms of outcomes and adverse effects.