David Sturdee

Recommendations for the management of postmenopausal vaginal atrophy.

Unlike hot flushes and night sweats which resolve spontaneously in time, atrophic symptoms affecting the vagina and lower urinary tract are often progressive and frequently require treatment. The prevalence of vaginal dryness increases as a woman advances through the postmenopausal years, causing itching, burning and dyspareunia, and sexual activity is often compromised. But, despite the various safe and effective options, only a minority (about 25% in the Western world and probably considerably less in other areas) will seek medical help. Some of this reluctance is due to the adverse publicity for hormone replacement therapy (HRT) over recent years that has suggested an increased risk of breast cancer, heart disease and stroke. But, regardless of whether these scares are justified, local treatment of vaginal atrophy is not associated with these possible risks of systemic HRT. Other reasons for the continued suffering in silence may be cultural and an understandable reluctance to discuss such matters, particularly with a male doctor, but the medical profession must also take much of the blame for failing to enquire of all postmenopausal women about the possibility of vaginal atrophic symptoms. Vaginal dryness can be helped by simple lubricants but the best and most logical treatment for urogenital atrophy is to use local estrogen. This is safe, effective and with few contraindications. It is hoped that these guidelines and recommendations, produced to coincide with World Menopause Day 2010, will help to highlight this major cause of distress and reduced quality of life and will encourage women and their medical advisers all over the world to seek and provide help. INTERNATIONAL MENOPAUSE SOCIETY WRITING GROUP D. F. Archer, R. Baber, C. Castelo Branco, T. J. de Villiers, A. Gompel, F. Guidozzi, K.-E. Huang, M. Kandil, S. Khandelwal, R. Lobo, R. M. Mostafa, R. E. Nappi, S. Palacios, N. Panay, A. Pines, J. A. Simon, S. O. Skouby, C. A. Stuenkel, D. W. Sturdee, L. Ulrich, P. Villaseca.

Updated 2013 International Menopause Society recommendations on menopausal hormone therapy and preventive strategies for midlife health

MediClinic Panorama and Department of Obstetrics and Gynecology, Stellenbosch University, Cape Town, South Africa; * Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel; † Queen Charlotte ’ s & Chelsea Hospital, and Chelsea and Westminster Hospital, London, UK; ‡ Department of Obstetrics and Gynecology, Pisa University Hospital, Pisa, Italy; * * Jones Institute, Eastern Virginia Medical School, Norfolk, VA, USA; † † Sydney Medical School, The University of Sydney, NSW, Australia; ‡ ‡ Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia; * * * UF de Gyn e cologie, Universit e Paris Descartes, AP-HP, H o tel-Dieu, Paris, France; † † † Departments of Health Research & Policy (Epidemiology) and of Neurology & Neurological Sciences, Stanford University, Stanford, CA, USA; ‡ ‡ ‡ Associate Dean for Clinical and Translational Research and Professor of Family Medicine-Las Vegas, University of Nevada School of Medicine, Las Vegas, NV, USA; * * * * Department of Obstetrics and Gynecology, Columbia University, New York, NY, USA; † † † † Unit e de Gyn e cologie M e dicale, H o tel Dieu, Paris, France; ‡ ‡ ‡ ‡ Heart of England NHS Foundation Trust, Solihull Hospital, Birmingham, UK

IMS Updated Recommendations on postmenopausal hormone therapy

The past decade has seen marked fluctuations inopinions concerning the merits and risks ofpostmenopausal hormone therapy. In July 2002,menopause management faced a major turningpoint when the first data from the Women’sHealth Initiative (WHI) trial were released. Thestudy was categorized as a primary preventiontrial for coronary heart disease, although the factthat mean age at recruitment was 63 years was notgiven enough importance at that time. WHIinvestigators concluded that hormone therapy(HT) was not cardioprotective, and, in fact, itsrisk–benefit ratio did not favor the use ofpostmenopausal hormones for prevention ofchronic diseases. As a result, there was a dramaticchange in prescription habits following recom-mendations to reserve HT for very symptomaticwomen, and to limit its use to the ‘shortestduration needed’ and ‘to the lowest effectivedosage’. This was the atmosphere in which theInternational Menopause Society (IMS) initiatedthe IMS Workshop held in Vienna (December2003) and the IMS Position Paper that was basedon the Workshop discussions. Looking at globalperspectives, and being independent of local orregional constraints imposed by official healthauthorities, this IMS Statement called for a morebalanced approach in the interpretation of thescientific data on hormone use that were availablein 2003. Since then, additional information hasbeen accumulated from both arms of the WHIstudy, observational trials and from other studies,allowing a more comprehensive review on allissues related to the use of hormones in thepostmenopausal period. In view of the above, theIMS Board decided that it is time to update the2004 Statement and to enlarge its scope tomenopause management and adult women’shealth in general. More than 30 experts from thevarious fields of menopause medicine reviewed thelatest information in a Workshop held in Budapestin February 2007.The following Recommendations express theviews of the IMS on the principles of hormonetherapy in the peri- and postmenopausal periods.Throughout the Recommendations, the term HTwill be used to cover all therapies includingestrogens, progestogens, combined therapies andtibolone.The previous IMS Statement in 2004 is stillvalid and serves as a basis for the current UpdatedRecommendations.We are aware of the geographical variationsrelated to different priorities of medical care,different prevalence of diseases, and country-specific attitudes of the public, the medicalcommunity and the health authorities towardmenopause management, which may all impacton hormone therapy. The following recommenda-tions, therefore, give a global and simple overviewthat serves as a common platform on issues relatedto the various aspects of hormone treatment.These Recommendations were reviewed and dis-cussed by representatives of more than 60National and Regional Menopause Societies fromall continents. These Recommendations can beeasily adapted and modified according to localneeds.

Menopausal symptoms in women treated for breast cancer: the prevalence and severity of symptoms and their perceived effects on quality of life.

Objectives To determine, first, the prevalence and severity of various symptoms related to estrogen deficiency in women within a few years of receiving treatment for breast cancer, second, how women perceive the effects of these symptoms on their quality of life and, third, what measures have been taken to relieve vasomotor symptoms. Methods Two hundred women (aged 29–65 years) who had received treatment for breast cancer within the last 5 years were included in this cross-sectional survey. Information was collected about their breast cancer treatment, menopausal symptoms (Menopausal Rating Scale), the perceived effects of menopausal symptoms on their and their partners quality of life and any treatments they were receiving for hot flushes. Results All but one woman reported at least one symptom related to the menopause (95.9% vasomotor; 83.3% psychological; 89.7% somatic). Current treatment with tamoxifen or previous chemotherapy did not influence the prevalence or the severity of hot flushes. Current antidepressant treatment was, however, significantly associated with a higher prevalence and severity of most menopausal symptoms, including hot flushes and sweats (p = 0.008). The severity of hot flushes and sweats was significantly correlated with self-assessed effects on overall quality of life (rs = 0.47); 56.4% of the respondents believed that menopausal symptoms had affected their partners quality of life, the strongest correlations being with severity of sexual symptoms (rs = 0.56) and vaginal dryness (rs = 0.5). Only 21% of women experiencing hot flushes were receiving any treatment for hot flushes, with most women describing no knowledge or poor knowledge of treatment options. Conclusions The majority of women receiving treatment for breast cancer report menopausal symptoms, which negatively correlate, not only with their own, but also with their partners quality of life. Most women experiencing hot flushes are not receiving treatment due to lack of both awareness and confidence in the existing treatment options.

Treatment of menopausal symptoms: what shall we do now?

During the past few years, many women and doctors have revised their opinions of hormone replacement therapy (HRT) for menopausal symptoms, and a substantial number of individuals have discontinued its use because of concerns about side-effects. Numerous alternatives to HRT are promoted, and assessment of the quality of evidence about the safety and effectiveness of these compounds can be difficult. In this Review, we summarise the data from studies addressing the efficacy, risks, and benefits of frequently prescribed treatments, and offer evidence-based clinical guidelines for the management of menopausal symptoms. Although few comparative studies exist, oestrogen alone or combinations of oestrogen and progestagen are likely to be the most effective treatments for menopausal hot flushes and vaginal dryness. Tibolone is as effective as HRT, however, and might also improve libido. For those who wish to avoid hormonal treatments, there are few effective options. Selective serotonin reuptake inhibitors might be effective in the very short term (less than 12 weeks) and are well tolerated. There is not enough evidence that any of the complementary therapies available are any better than placebo for menopausal vasomotor symptoms, and few safety data exist.

Testosterone treatment of HSDD in naturally menopausal women: the ADORE study

Objective To evaluate the efficacy and safety of a transdermal testosterone patch (TTP, 300 μg/day) in naturally menopausal women with hypoactive sexual desire disorder (HSDD). Methods A total of 272 naturally menopausal women, predominantly not using hormone therapy, were randomized in this 6-month, placebo-controlled, double-blind, multicenter study to receive twice weekly either TTP or an identical placebo. Efficacy endpoints measured were the 4-week frequency of satisfying sexual episodes (SSE) using the Sexual Activity Log, the sexual desire domain of the Profile of Female Sexual Function and distress by the Personal Distress Scale. Safety was assessed by adverse events, laboratory parameters and hormone levels. Results The TTP group demonstrated significant improvements in SSE (p = 0.0089) as well as in sexual desire (p = 0.0007) and reduced personal distress (p = 0.0024) versus placebo at 6 months (intent-to-treat analysis, n = 247). The results were significant for all three endpoints in the subgroup (n = 199) not using hormone therapy. Similar numbers of women treated with placebo and TTP discontinued (n = 39, 27.5% vs. n = 26, 20%), reported adverse events (including application site reactions) (n = 101, 71.1% vs. n = 81, 62.3%) and withdrew due to adverse events (n = 20, 14.1% vs. n = 9, 6.9%). No clinically relevant changes were noted in laboratory parameters. Serum free and total testosterone levels increased from baseline in the TTP group (geometric means 5.65 pg/ml and 67.8 ng/dl, respectively, at week 24) within the physiological range; no changes were seen in estradiol and sex hormone binding globulin levels. Conclusions TTP was effective in treating HSDD and improving sexual function in this study of naturally menopausal women with and without concurrent hormone therapy.

The menopausal hot flush--anything new?

Although the hot flush is generally recognised by women and the medical profession as the most characteristic and often a very distressing symptom of the climacteric, it remains an enigma. The physiological changes associated with the hot flush are different from any other flushing condition, with an increased peripheral blood flow, increased heart rate and in particular a decrease in galvanic skin resistance, which is unique to the flush. Flushing occurs as a result of disturbance of the temperature regulating mechanism situated in the hypothalamus, and probably a reduction in the thermoneutral zone, within which fluctuations of basal body temperature do not provoke compensatory vascular responses. Many factors have been implicated, including hormone releasing factors, gonadotrophins and neurohumorals. However, the role of oestrogen is critical and the clinical value of oestrogen therapy is well established and has been confirmed by a Cochrane review. Nevertheless, the precise mechanism by which reduced circulating levels of oestrogen are involved in causing the flush has not yet been established. Priming with oestrogen seems to be an essential pre-requisite for flushing, as young women with ovarian dysgenesis and very low circulating levels of oestrogen never have hot flushes unless they are given oestrogen replacement therapy, which is later discontinued. Oestrogen antagonist activity by selective oestrogen receptor modulators such as tamoxifen and raloxifene can also cause flushing. A link with gonadotrophins is demonstrated by a temporal association of flushes with the pulsatile release of luteinising hormone (LH). However, if LH pulses are eliminated by GnRH analogue, the frequency of flushing is not altered, which confirms that LH is merely associated with the flush rather than being causative. It is probable that the flush is initiated by a supra-pituitary mechanism which is influenced by the hypothalamic factors responsible for pulsatile LH release. A variety of chemical pathways have been proposed involving serotonin, noradrenalin and dopamine. Trials of drugs that selectively inhibit the re-uptake of serotonin and noradrenalin have shown some beneficial effects, as also has gabapentin, but often the results have been disappointing, and certainly less than the response seen with oestrogen or tibolone. The prevalence of hot flushes varies considerably around the world and is less in the Far East than in the west. Differences in diet and in particular the intake of phytoestrogens has been implicated and many studies have tried to establish whether dietary supplementation with phytoestrogens might be a suitable alternative to conventional hormone replacement therapy (HRT). So far, the results are disappointing. Other lifestyle measures such as avoiding alcohol, caffeine and spicy foods, keeping the core body temperature cool, paced respiration, taking exercise and even acupuncture may help. Hot flushes remain a major cause of reduced quality of life in a large proportion of menopausal women, but perhaps because they are not fatal and are usually self-limiting, there has been rather limited research or clinical interest. However, for the increasing number of women being treated with tamoxifen for breast cancer, and for whom oestrogen will usually be contra-indicated or unsuitable, there is an urgent need to identify the underlying mechanism so that appropriate, specific and safe non-oestrogen therapy can be offered to improve their quality of life.

Guidelines for hormone treatment of women in the menopausal transition and beyond

Recent communications regarding estrogen or estrogen + progestin treatment and clinical cardioprotection, breast cancer risk and cerebral aging have produced considerable confusion and concerns among women, care-givers and the media. The actions of the United States’ Food and Drug Administration (FDA) and other National Safety of Medicine Boards, such as the European Medicine Evaluation Agency (EMEA), in response to publication of data from the Women’s Health Initiative (WHI) and the Million Women Study (MWS), have also raised concerns. The Executive Committee of the International Menopause Society (IMS) has considered position statements presented at the Fourth Workshop of the IMS, December 2003 and reviewed all presently available information from observational studies, randomized controlled trials (RCTs) and preclinical research, and wishes to point out the following:

Mid-age health in women from the Indian subcontinent (MAHWIS): general health and the experience of menopause in women

Objectives First, to examine the experience of menopause and quality of life in a migrated Asian population from the Indian subcontinent living in Birmingham, UK, and, second, to compare their experience with a matched sample of Caucasian women living in the same geographical area and also with a sample of Asian women with similar socioeconomic background living in Delhi, India. Methods In this cross-sectional study of 153 peri- and postmenopausal women aged 45–55 years, 52 Asian women originating from the Indian subcontinent living in Birmingham (UKA, mean age 51.4 years), 51 Caucasian women (UKC, mean age 52.3 years) and 50 Asian women living in Delhi, India (DEL, mean age 49.72 years) were interviewed to collect information about their lifestyle, general health, menopause experience and help-seeking behavior. The Womens Health Questionnaire and the Menopause Representation Questionnaire (both translated and linguistically validated in Hindi) were used to examine the prevalence of physical and emotional symptoms and the extent to which these were attributed to the menopause. Results The two Asian groups (UKA, DEL) reported poorer health and generally more physical and emotional symptoms than the UKC group. However, for menopausal symptoms (hot flushes and night sweats) there was a different pattern; the DEL group reported significantly fewer symptoms compared to the UKA and UKC groups (hot flushes: UKC 60.8%, UKA 75%, DEL 32% (p < 0.001); night sweats: UKC 50%, UKA 56.9%, DEL 24% (p = 0.002)). The prevalence of vaginal dryness was highest in the UKA group and lowest in the DEL group (UKC 21.6%, UKA 38.2%, DEL 7.3% (p = 0.005)). The number of symptoms attributed to menopause was significantly lower in the DEL group (9.3 ± 7.8) compared to the two UK groups (UKC 18.9 ± 7.4, UKA 19.8 ± 10.7), but the UKA women tended to attribute some physical symptoms to the menopause such as breathlessness, weight gain and stiff joints that might have other causes. Conclusions The UK Asian womens experience of the menopause is more similar to the Caucasian women in the UK than that of the women in Delhi. However, Asian women living in the UK and the Indian subcontinent shared the experience of poor health and reports of more physical and emotional symptoms in general. The possible reasons for these differences are discussed.

Thermography of menopausal hot flushes

The skin temperature changes associated with menopausal hot flushes have been examined by thermography on a small group of patients. The subjective sensation of heat during a flush seems to be out of proportion to the actual skin temperature increase which was only about 1 degrees C on the face, neck and upper chest during this study. The increased temperature on the cheeks often persisted for several minutes after the symptoms of the flush had subsided, whereas sweating on the forehead produced a more rapid local cooling effect. Sequential temperature changes were portrayed by using an AGA Thermovision Model 680 Medical System with a colour isotherm attachment. This study provided colourful objective evidence that the symptoms of menopausal flushing is associated with an increase of skin temperature which may be monitored by thermography.