Hormone replacement therapy in women treated for gynaecological malignancy.

Can we prescribe hormone replacement therapy (HRT) safely for women, with postmenopausal complaints who were treated for a gynaecological malignancy? Only three retrospective studies have investigated this issue in endometrial cancer patients. No recurrences or deaths occurred in these treated groups. However, the physician introduced bias through the selection of favourable groups. At present, combined estrogen and progestogen therapy is probably not contra-indicated in endometrial cancer stage I and probably also not in stage II, although so far there is only circumstantial evidence. Squamous cell cancers of the cervix, vulva, and vagina are unlikely to be influenced by HRT. In the only study available of women with ovarian cancer, < or = 50 years, estrogen replacement therapy did not have a negative influence on (disease-free) survival. According to the data currently available, no evidence exists that HRT adversely influences survival and overall survival after treatment for ovarian cancer. In general, adenocarcinomas of the cervix and leiomyosarcomas of the uterus may be managed such as the adenocarcinomas of the uterus. During the last 25 years, HRT has been shown to substantially reduce the risk of cardiovascular diseases, osteoporotic fractures and colon carcinoma. On the other hand there is a significant increase of the risk in breast cancer with prolonged use of > 5 years. Re-evaluation of the current view that HRT should no be given to women treated for a gynaecological malignancy is strongly warranted after evaluating the advantages and the disadvantages of HRT use in each individual patient. Long-term HRT in women treated for a gynaecological cancer must be based on the medical history of the individual patient (and her family).     

Hormone replacement therapy in Norwegian women, 1996-1997.

OBJECTIVES: To assess the prevalence of hormone replacement therapy (HRT) among Norwegian women and examine factors related to use. MATERIALS AND METHODS: A random sample of 18,199 Norwegian women aged 45-64 years responded to a postal questionnaire in 1996-1997. The questionnaire included questions about menstruation status and fertility, oral contraceptives (OC) and HRT use, lifestyle, health and socio-economic status. The response rate was 60%. RESULTS: Overall prevalence of ever using systemic or local HRT was 43.9%. Current use was reported by 31.9% of the women. The highest prevalence was in the age group of 55-59 years where 57.4% reported ever use, and 43.1% current use. Mean duration of use among current users was 4.6 years. More than 60% of the women were classified as postmenopausal, two-thirds of them naturally postmenopausal. The prevalence of ever using HRT was 51.8%. Prevalence of use was higher among earlier OC users, smokers, lean women and in households with high income. Among older women, users had a higher educational level than non-users, while this difference disappeared among the youngest of the women. Fixed combinations of estradiol and noretisteroneacetate either cyclic or continuous, are used by six out of ten users. CONCLUSIONS: Our results confirm the increasing trend in sales of estrogens in Norway and suggest that user patterns are changing. More than four out of ten women aged 45-64 years reported ever use of HRT, and one out of three reported current use. Socio-economic differences between users and non-users seem to disappear among women under 55 years of age, but persist in the older age groups. Short time use still dominates.     

Hormone replacement therapy: use patterns in 51-year-old Danish women

A survey based on a postal questionnaire sent to all women born in 1936 living in four Copenhagen suburbs (n = 597, response rate = 88%) revealed an overall prevalence of hormone replacement therapy (HRT) use of 22% and a cumulative incidence of 37%. This paper describes the use of HRT in this population and the patterns of exposure to treatment. Our results indicate that the use of HRT, particularly combined oestrogen-progestogen therapy, is increasing and is being initiated during the pre-menopause. Climacteric complaints were the main reason for starting treatment; only a minority of the respondents were motivated by prophylactic considerations. Forty percent discontinued treatment, the majority stating that they had done so because of unpleasant adverse reactions or lack of effect.     

Hormone replacement therapy and hemostasis: effects in Brazilian postmenopausal women

OBJECTIVE: To evaluate the impact that administration of transdermal estradiol gel combined with medroxyprogesterone acetate (MPA) has on hemostasis. METHODS: In this open prospective longitudinal study, thirty postmenopausal women received transdermal estradiol gel (1 mg/day) continuously combined with oral MPA (5 mg/day) for 12 days/month. The following parameters were determined: prothrombin time (PT), activated partial thromboplastin time (aPTT), factors VII, X, and XII activity, fibrinogen levels, thrombin-antithrombin complex levels, protein C and S antigen, antithrombin activity, plasminogen activator inhibitor type 1 (PAI-1) antigen, tissue-type plasminogen activator (t-PA) antigen, plasminogen activity and fibrin degradation products (FbDP) antigen. They were evaluated before and after 6 months of treatment. RESULTS: There was a significant decrease in factor VII activity (P=0.001), factor X activity (P=0.016), protein C antigen (P=0.022), antithrombin activity (P=0.025), plasminogen activity (P=0.023), t-PA antigen (P=0.043) and FbDP antigen (P=0.048) compared with baseline values. CONCLUSION: The results suggest that the treatment with transdermal estradiol gel combined with MPA avoids any major activation of coagulation and does not produce any overall effect on fibrinolysis. Therefore, this treatment might provide interesting effects on hemostasis in postmenopausal Brazilian women.     

Hormone replacement therapy and cognitive function in postmenopausal women

ObjectivesThe study investigated the effect of hormone replacement therapy (HRT) on cognitive processes in healthy, naturally postmenopausal women.MethodParticipants were 64 volunteer postmenopausal women (27 in HRT, 37 in non-HRT group). Groups were matched for age, level of education and postmenopausal period. Duration of HRT was more than 12 months. Cognitive processes were measured through 44 scores obtained from Wechsler Memory Scale-Revised, Line Orientation Test, Cancellation Test and Raven Standard Progressive Matrices. All of these tests had been studied with respect to their psychometric properties in the Turkish culture [for review, Karakaş S. BİLNOT battery: research and development of neuropsychological tests. Ankara, Turkey: Dizayn Ofset; 2004].ResultsMultivariate analysis of variance was performed where HRT and estradiol level were predictive (independent) variables and test scores were predicted (dependent) variables. The studied variables did not have a significant effect on a broad spectrum of neuropsychological scores that measured immediate and delayed visual and verbal memory, visuospatial perception and orientation, sustained attention/vigilance, visual search and scan, impulsivity and response speed, executive functions and general intelligence. Logistic regression analysis demonstrated a prediction rate of 86.89% of HRT status; the model was, however, based on four scores whose scientific relevance could not at this point be ascertained.ConclusionThe research design of the present observational study applied control techniques to demographic (age, level of education), menopausal (length of menopausal period, duration of HRT), and hormonal variables. The cognitive changes that some studies found concerning the effect of replacement therapy could not be found when the potentially confounding variables were thus controlled.     

Hormone replacement therapy in women with pre-existing hyperpigmented lesions

OBJECTIVES: This study was performed to determine whether skin pigmentation is darkened after hormone replacement therapy (HRT). METHODS: The color of hyperpigmentary lesions and control sites before and after 1, 2, and 3 months of HRT was measured. RESULTS: All of the three tested sites showed no significant pigment alteration in 3 months of follow up after starting HRT (P>0.05). Age, duration of menopause, and sex hormone levels did not correlate with pigmentation level. CONCLUSIONS: Pigmentation changes after HRT are not significantly associated with the treatment. This finding suggests that low-dose estrogen replacement therapy does not induce pigmentation changes alone and that differences in individual susceptibility and end organ responsiveness or other multiple factors in addition to the sex hormone may be responsible for the development and darkening of hyperpigmentary lesions.     

Hormone replacement therapy and urinary prostaglandins in postmenopausal women

The objective of the study was to observe the effects of hormone replacement therapy upon urinary prostaglandin E₂ and prostaglandin F_2α levels in postmenopausal patients. A total number of 55 women were enrolled in this study and 15 premenopausal (PreM) healthy subjects constitute the control group. A total of 40 patients at least 12 months after their natural menopause were divided into two groups: 15 of them was not medicated hormone replacement therapy (which composed NRHRT group) while 25 of the rest, received conjugated estrogen (Premarin) 0.625 mg/day orally plus medroxyprogesterone acetate (Farlutal) 10 mg/day orally built up the RHRT group. PGE₂ and PGF_2α levels were measured with PGE₂ [¹²⁵I] and PGF_2α [³H] RIA kits. Statistical significance was analyzed by Student’s t-test for impaired data. NRHRT and RHRT patients had had increased urinary PGE₂ levels when compared with PreM (P<0.001). HRT caused a significant decrease in PGE₂ levels in menopausal women (P<0.001). Urinary PGF_2α values of NRHRT and RHRT were significantly lower (P<0.001) in comparison with PreM group. There was no difference in PGF_2α values between two postmenopausal groups. HRT given to postmenopausal patients might have a positive impact on prostaglandins and therefore on bone turnover in a series of various mechanisms.     

Hormone replacement therapy may alleviate sleep apnea in menopausal women: a pilot study.

OBJECTIVE: The incidence of sleep apnea syndrome (SAS) in women increases after menopause. Progestins alone do not alleviate SAS in menopausal women. However, progestins may require concomitant estrogen administration and estrogen alone may stimulate breathing during sleep. To test these hypotheses, we studied the effects of estrogen alone and estrogen combined with progestin on SAS in menopausal women, using a prospective, cross-over, inception cohort study. DESIGN: In this pilot study, five women who developed SAS after menopause underwent 2 nights of polysomnography to obtain a baseline, then returned for polysomnography after 3-4 weeks of taking micronized 17 beta-estradiol (E2) and after 10-12 days of taking E2 combined with medroxyprogesterone acetate (E2 + P). Sleep stages were scored according to Rechtshaffen and Kales, frequency and length of apneas were recorded for each subject each night, and the data were analyzed by Student's t test. RESULTS: E2 and E2 + P both reduced the Respiratory Distress Index. E2 also raised the lowest oxygen desaturation associated with apneic episodes. Total minutes of rapid eye movement sleep increased, and the number of waking episodes decreased when the women were taking E2 and E2 + P, as previously reported. CONCLUSIONS: Within 1 month after initiating E2 or E2 + P, SAS was reduced in all patients. The Respiratory Distress Index decreased by 25%, and the addition of progestin brought the SAS reduction to 50% in this pilot study. A randomized study in a large group of patients is justified by the findings of this study. Because SAS increases the risk of cardiovascular disease and fatal accidents, the amelioration of SAS by sex steroid hormones could have significant implications for the health of menopausal women.     

Hormone replacement therapy improves arterial stiffness in normotensive postmenopausal women

Objectives: Aortic stiffness, determined by the pulse wave velocity (PWV), is an independent marker of cardiovascular risk. PWV is mainly influenced by age-associated alterations of arterial wall structure and blood pressure (BP). To determine the impact of hormone replacement therapy (HRT) on arterial compliance in normotensive, postmenopausal women, we examined the effects of HRT on PWV. Methods: Fifty-six postmenopausal women aged 50–70 years were recruited into the present retrospective study from the patients visiting our menopause clinic. Twenty-seven women who were prescribed HRT (14 on estrogen alone and 13 on estrogen plus progestogen) for several months to 6 years and an age-matched group of 29 women not on HRT were studied (Study 1). Nine postmenopausal women were also studied before and at 4 weeks of the treatment of estrogen replacement therapy (ERT) (Study 2). Brachial to ankle PWV (baPWV), which is correlated with aortic PWV, was determined using an automatic device, BP-203PRE. Results: In Study 1, PWV was significantly correlated with age in both groups (controls: r=0.392, P=0.035; HRT group: r=0.471, P=0.013), and HRT significantly lowered the PWV value at all ages examined (Mean±S.D. of baPWV in controls: 1382.2±114.1; HRT: 1245.3±124.8, P=0.0001). In Study 2, baPWV decreased significantly after ERT (P<0.05), without a significant change in systolic BP (P=0.851). Conclusions: Estrogen appears to improve arterial compliance independently of BP within 4 weeks.     

Hormone replacement therapy: the perspectives for the 21st century.

Nowadays different lines of evidence demonstrate the benefits of postmenopausal hormone replacement therapy (HRT). HRT is extremely effective in treating subjective symptoms and can really improve the quality of life of climacteric women. HRT and dementia: Estrogens are potentially relevant to the pathogenesis and treatment of Alzheimer's disease. The effects of different progestogens on cognitive functions and Alzheimer's disease are largely unknown. The prevention of Alzheimer disease might be a major indication to long term HRT. Large prospective, randomized trials will confirm these preliminary data. HRT and osteoporosis: HRT has been strongly correlated with higher bone mineral density and lower fracture incidence. Definite answers in terms of minimum effective dosages, timing and duration of HRT for fracture prevention are needed. HRT and cardiovascular disease: Different lines of evidence suggest that HRT can exert cardioprotective effects with substantial reduction of morbidity and mortality for cardiovascular disease in postmenopausal women. The effects and the role of progestogens in cardiovascular disease prevention are still debated. Prospective, randomized, controlled studies are needed to assess the impact of different HRT regimens on cardiovascular events. HRT and cancer: The major issue in the relationship between HRT and cancer is breast cancer. Long-term and current HRT use are followed by a slight, though significant increase in the risk of breast cancer. Progestogens can modify the cellular response of normal as well as cancer breasts. The possible protective effect of continuous progestogen addition is very interesting and needs further investigation. Alternative to classical HRT: Selective estrogen receptor modulators (SERM). SERMs such as raloxifene (RAL) are a new class of drugs that exert site specific estrogenic or antiestrogenic effects in different target tissues. RAL prevents bone loss and reduces serum cholesterol in postmenopausal women. In contrast to estrogen RAL does not stimulate breast or uterine tissues. In vitro RAL is highly effective at inhibiting the growth of estrogen-dependent breast adenocarcinoma cells. SERMs are expected to represent a major breakthrough for postmenopausal health. CONCLUSION: HRT can be offered either as a preventive tool or as individualized care on the basis of personal needs. New therapeutic options like the SERMs will offer a substantial medical advancement for the treatment of postmenopausal women.