The role of testosterone in menopausal hormone treatment. What is the evidence?

About 40% of postmenopausal women have decreased sexual desire, causing distress. Estrogen therapy attenuates vaginal complaints but has no effect on sexual desire. Although sexual function has been linked to testosterone, there is no clear relation between sexual desire and circulating levels of testosterone. Nevertheless, treatment with transdermal (patch) testosterone improved sexual function in several randomized controlled trials. Women with hypoactive sexual desire disorder who were treated with testosterone reported more satisfying sexual episodes and sexual desire compared with the placebo group. Adverse effects were mild. However, there is no testosterone drug designed for women available on the European market. Consequently, women who opt for testosterone treatment have to use preparations made for men with a high drug concentration. Adequate dosage for women is therefore challenging. A trial of 5 mg transdermal testosterone (gel or cream) daily or less has been suggested, followed by close monitoring of side effects and hormone level.

EMAS clinical guide: selective estrogen receptor modulators for postmenopausal osteoporosis.

Osteoporosis and the resulting fractures are major public health issues as the world population is ageing. Various therapies such as bisphosphonates, strontium ranelate and more recently denosumab are available. This clinical guide provides the evidence for the clinical use of selective estrogen modulators (SERMs) in the management of osteoporosis in postmenopausal women.

EMAS position statement: Vitamin D and postmenopausal health.

INTRODUCTION: There is emerging evidence on the widespread tissue effects of vitamin D. AIMS: To formulate a position statement on the role of vitamin D in postmenopausal women. MATERIALS AND METHODS: Literature review and consensus of expert opinion. RESULTS AND CONCLUSIONS: Epidemiological and prospective studies have related vitamin D deficiency with not only osteoporosis but also cardiovascular disease, diabetes, cancer, infections and neurodegenerative disease. However the evidence is robust for skeletal but not nonskeletal outcomes where data from large prospective studies are lacking. The major natural source of vitamin D is cutaneous synthesis through exposure to sunlight with a small amount from the diet in animal-based foods such as fatty fish, eggs and milk. Vitamin D status is determined by measuring serum 25-hydroxyvitamin D [25(OH)D] levels. Optimal serum 25(OH)D levels are in the region of 30-90 ng/mL (75-225 nmol/L) though there is no international consensus. Levels vary according to time of the year (lower in the winter), latitude, altitude, air pollution, skin pigmentation, use of sunscreens and clothing coverage. Risk factors for low serum 25(OH)D levels include: obesity, malabsorption syndromes, medication use (e.g. anticonvulsants, antiretrovirals), skin aging, low sun exposure and those in residential care. Fortified foods do not necessarily provide sufficient amounts of vitamin D. Regular sunlight exposure (without sunscreens) for 15 min, 3-4 times a week, in the middle of the day in summer generate healthy levels. The recommended daily allowance is 600 IU/day increasing to 800 IU/day in those aged 71 years and older. Supplementation can be undertaken with either vitamin D2 (ergocalciferol) or vitamin D3 (cholecalciferol) with monitoring depending on the dose used and the presence of concomitant medical conditions such as renal disease.

EMAS position statement: Managing menopausal women with a personal or family history of VTE.

INTRODUCTION: Venous thromboembolism (VTE), including deep venous thrombosis (DVT) and pulmonary embolism (PE), is a serious cardiovascular event whose incidence rises with increasing age. AIMS: To formulate a position statement on the management of the menopause in women with a personal or family history of VTE. MATERIAL AND METHODS: Literature review and consensus of expert opinion. RESULTS AND CONCLUSIONS: Randomized controlled trials have shown an increased risk of VTE in oral hormone therapy (HT) users. There are no randomized trial data on the effect of transdermal estrogen on VTE. Recent observational studies and meta-analyses suggest that transdermal estrogen does not increase VTE risk. These clinical observations are supported by experimental data showing that transdermal estrogen has a minimal effect on hepatic metabolism of hemostatic proteins as the portal circulation is bypassed. A personal or family history of VTE, especially in individuals with a prothrombotic mutation, is a strong contraindication to oral HT but transdermal estrogen can be considered after careful individual evaluation of the benefits and risks. Transdermal estrogen should be also the first choice in overweight/obese women requiring HT. Observational studies suggest that micronized progesterone and dydrogesterone might have a better risk profile than other progestins with regard to VTE risk. Although these findings should be confirmed by randomized clinical trials, they strongly suggest that both the route of estrogen administration and the type of progestin may be important determinants of the overall benefit-risk profile of HT.

EMAS position statement: Managing the menopause in the context of coronary heart disease.

INTRODUCTION: Cardiovascular disease (CVD) including coronary heart disease (CHD) and stroke is the most common cause of female death. Premenopausal CHD is very rare but when women enter the menopause the incidence of CHD increases markedly. CHD presents 10 years later in women than in men. The reason is still unclear but the protective effects of estrogens have been suggested. AIMS: To formulate a position statement on the management of menopause women in the context of coronary heart disease. MATERIALS AND METHODS: Literature review and consensus of expert opinion. RESULTS AND CONCLUSIONS: Based on long term randomized placebo-controlled studies hormone therapy (HT) is not recommended for the primary or secondary prevention of CHD in postmenopausal women. In most countries the only indication for HT is the treatment of menopausal symptoms. Women with known CHD or with many coronary risk factors seeking HT because of troublesome climacteric symptoms should be evaluated for their individual baseline risk of developing breast cancer, venous thromboembolism and CHD recurrence. The same applies to non hormone therapy-based treatments where long term clinical studies are lacking. Risks should be weighed against expected benefit from symptom relief and improved quality of life. The lowest effective estrogen dose should be used during the shortest possible time. Transdermal administration is preferred if risk factors for VTE exist. Different progestogens might differ in their cardiovascular effects. Observational studies suggest that micronized progesterone or dydrogesterone may have a better risk profile than other progestogens with regard to thrombotic risk.

EMAS position statement: Bone densitometry screening for osteoporosis.

INTRODUCTION: Osteoporosis and its consequent fractures is a major public health problem. AIM: To formulate a position statement on the use of bone densitometry in screening postmenopausal women for osteoporosis and in their management. MATERIALS AND METHODS: Literature review and consensus of expert opinion. RESULTS AND CONCLUSIONS: Bone densitometry has an important role in screening postmenopausal women for osteoporosis. For higher sensitivity and specificity, there may be a stronger case for screening in later life, depending on the extent to which risk factors add to the value of bone mineral density tests.

EMAS position statement: Managing women with premature ovarian failure.

INTRODUCTION: Premature ovarian failure (also known as premature menopause) is defined as menopause before the age of 40. It can be "natural" or "iatrogenic" such as after bilateral oophorectomy. It may be either primary or secondary. In the majority of cases of primary POF the cause is unknown. Chromosome abnormalities (especially X chromosome), follicle-stimulating hormone receptor gene polymorphisms, inhibin B mutations, enzyme deficiencies and autoimmune disease may be involved. Secondary POF is becoming more important as survival after treatment of malignancy through surgery, radiotherapy and chemotherapy continues to improve. AIM: To formulate a position statement on the management of premature ovarian failure. MATERIALS AND METHODS: Literature review and consensus of expert opinion. RESULTS AND CONCLUSIONS: Diagnosis should be confirmed with an elevated FSH greater than 40 IU/L and an estradiol level below 50 pmol/L in the absence of bilateral oophorectomy. Further assessment should include thyroid function tests, autoimmune screen for polyendocrinopathy, karyotype (less than 30 years of age) and bone mineral density. Untreated early ovarian failure increases the risk of osteoporosis, cardiovascular disease, dementia, cognitive decline and Parkinsonism. The mainstay of treatment is hormone therapy which needs to be continued until the average age of the natural menopause. With regard to fertility, while spontaneous ovulation may occur the best chance of achieving pregnancy is through donor oocyte in vitro fertilization. It is essential that women are provided with adequate information as they may find it a difficult diagnosis to accept. It is recommended that women with POF are seen in a specialist unit able to deal with their multiple needs.

EMAS position statement: Managing the menopause in women with a past history of endometriosis.

INTRODUCTION: Endometriosis is a common disease in women of reproductive age. The symptoms usually disappear after a natural or a surgical menopause. Estrogen-based hormone therapy is required in women with premature or early menopause until the average age of the natural menopause and should be considered in older women with severe climacteric symptoms. However use of hormone therapy raises concerns about disease recurrence with pain symptoms, need for surgery and possibly malignant transformation of residual endometriosis. AIM: To formulate a position statement on the management of the menopause in women with a past history of endometriosis. MATERIALS AND METHODS: Literature review and consensus of expert opinion. RESULTS AND CONCLUSIONS: The data regarding hormone therapy regimens are limited. However it may be safer to give either continuous combined estrogen-progestogen therapies or tibolone in both hysterectomised and nonhysterectomised women as the risk of recurrence may be reduced. The risk of recurrence with hormone therapy is probably increased in women with residual disease after surgery. Management of potential recurrence is best monitored by responding to recurrence of symptoms. Women not wanting estrogen or those who are advised against should be offered alternative pharmacological treatment for climacteric symptoms or skeletal protection if indicated. Herbal preparations should be avoided as their efficacy is uncertain and some may contain estrogenic compounds.

EMAS position statement: managing obese postmenopausal women.

INTRODUCTION: Obesity is a public health problem, with overweight individuals representing approximately 20% of the adult world population. Postmenopausal status is associated with higher prevalence of obesity, as 44% of postmenopausal women are overweight, among whom 23% are obese. Obesity often co-exists with other diseases, the most important being diabetes mellitus, dyslipidemia and hypertension. Furthermore, obesity increases the risk of gynecologic cancer, cardiovascular disease, venous thromboembolism, osteoarthritis and chronic back pain. AIM: To formulate a position statement on the management of the menopause in obese women. MATERIALS AND METHODS: Literature review and consensus of expert opinion. RESULTS AND CONCLUSIONS: Obese women seeking hormone therapy should be evaluated for their individual baseline risk of developing breast cancer, cardiovascular disease and venous thromboembolism. These risks should be weighed against expected benefit from symptom relief, improved quality of life and osteoporosis prevention. The lowest effective estrogen dose should be used (CEE 0.300-0.400 mg or estradiol 0.5-1 mg orally daily or 25-50 microg estradiol transdermally). With regard to progestogens, although no RCT data exist, there are observational studies showing that micronized progesterone or dydrogesterone may have a better risk profile with respect to breast cancer risk. There are no RCT data comparing various progestogens with regard to VTE risk. There are observational data, however, suggesting that micronized progesterone or pregnane derivatives may be associated with a lower VTE risk in postmenopausal women taking HT compared to nonpregnane derivatives. There is a rationale in suggesting the use of transdermal HT in obese women, since this route of administration has been associated with a lesser risk of venous thromboembolism than oral therapy.

EMAS position statement: managing the menopause in women with epilepsy.

INTRODUCTION: Epilepsy is a major public health problem worldwide which is clinically characterized by recurrent seizures. AIM: The aim of this position statement is to provide evidence-based advice on management of the menopause in postmenopausal women derived from the limited data available. MATERIALS AND METHODS: Literature review and consensus of expert opinion. RESULTS AND CONCLUSIONS: Women with epilepsy may undergo an earlier natural menopause, between 3 and 5 years depending on seizure frequency, but the data are limited. Data regarding the effects of the perimenopause and menopause on epilepsy are conflicting: some studies show an increased risk of seizures but others do not. With regard to hormone therapy (HT) one study has shown an increase in seizures with oral therapy with conjugated equine estrogens and medroxyprogesterone acetate, but no data are available for other regimens. Women starting HT should be closely monitored as their antiepileptic drug (AED) needs may change. As vitamin D and calcium metabolism can be affected by AEDS, supplements should be considered. Herbal preparations should be avoided as their efficacy is uncertain and they may interact with AEDs.

[Attitudes to estrogen replacement therapy among Norwegian women]. / Norske kvinners holdninger til bruk av østrogentilskudd.

BACKGROUND: The aim of the study was to investigate women's attitudes towards hormone treatment (HT), their judgment of the various sources of information, and their knowledge of indications for HT. METHODS: We posted questionnaires to 1000 Norwegian women between 45 and 60 years of age, randomly selected from the National Register. We received replies from 386 women (38.6%). RESULTS: Of those who replied, 28% reported that they were currently using HT, 22% were previous users, 24% were considering starting, whereas 26% refused ever to use HT. One half of current and previous users had obtained their prescriptions from a gynaecologist, the other half from their general practitioner. Mean age at start of HT was 47 years. 65% of the women started the medication before menopause. The women thought HT to be useful for treatment of hot flushes, prevention of osteoporosis, well-being, improved mood and sex life. The women were also asked about the rating of importance that they would give to the various sources of information. The highest ratings were given to their gynaecologist or general practitioner. Also reading about HT and the opinion of other health personnel obtained high ratings. CONCLUSIONS: The indications for HT given by the women correspond well with the prevailing guidelines. The recent observation about a possible negative effect of HT on cardiovascular disease seems to have reached the respondents. Many women begin to use HT several years before menopause.

Inhibin A and B as markers of menopause: a five-year prospective longitudinal study of hormonal changes during the menopausal transition.

OBJECTIVES: A more direct and precise hormonal marker of the menopause has been required for some time. The aim of this study was to identify the most accurate marker of the menopause, based on analyses of inhibin A and B, FSH, LH and estradiol (E(2)), among 59 healthy women without hormonal treatment during the perimenopause and early postmenopause. METHODS: Fifty-nine women, aged 46-56 years (mean age 51.2 years), were examined annually for 5 years during the menopausal transition and had venous blood drawn simultaneously for later analyses of the above-mentioned hormones. RESULTS: Inhibin A showed a steady decline from at least 4 years before the final menstrual period (FMP) until 1 year before menopause, whereas inhibin B had a shorter lasting decline from year 3 to year 2 before menopause, concomitant with a rise in FSH and LH. CONCLUSION: The present study confirmed previous observations that inhibin A had a continuous decline starting before the decline of inhibin B, suggesting that an increasing part of the cycle was anovulatory. The fall in inhibin B and the increase in FSH constitute markers of ovarian aging. One year prior to menopause neither inhibin A nor inhibin B could be detected. The disappearance of these peptide hormones is an important predictor of the approaching menopause.