Effects of hormone replacement therapy in bone resorption, in post-menopausal women

BACKGROUND: The effects of different therapies on bone loss rate can be measured using biochemical markers of bone resorption such as urinary hydroxyproline. AIM: To study the effects of hormone replacement therapy on urinary hydroxyproline in postmenopausal women. PATIENTS AND METHODS: Eighty three postmenopausal women without hormone replacement therapy, 54 postmenopausal women receiving hormone replacement therapy and 16 premenopausal women (considered as the control group) were studied. Hydroxyproline was measured in an early morning urine sample, after one day of diet without meat or gelatin. RESULTS: Urinary hydroxyproline in premenopausal women was 33.7 +/- 7.9 mg/g creatinine. The figure for postmenopausal women with hormonal replacement therapy was 33.7 +/- 5.9 mg/g creatinine. Postmenopausal women without replacement therapy had an urinary hydroxyproline of 47.4 +/- 8.5 mg/g creatinine, significantly higher than that of premenopausal and supplemented women. In 21 postmenopausal women, hydroxyproline was measured before and after three months of replacement therapy, values decreased 35.5 +/- 11% in this period and there was a direct correlation between initial values and the degree of reduction (r = 0.69, p < 0.001). CONCLUSIONS: Postmenopausal women receiving hormone replacement therapy have a urinary hydroxyproline excretion similar to that of premenopausal women.     

For patients: hormone replacement therapy

Paediatric firearm injuries in the UK are uncommon. We present two children with BB-gun pellets in the parapharyngeal space who were managed conservatively and remained asymptomatic 6 months after the gunshot injury. The management of asymptomatic firearm injuries in children is discussed and a literature review included.     

Mammographic changes after hormone replacement therapy in patients who have undergone breast irradiation

OBJECTIVE: We examined three patients who began hormone replacement therapy after lumpectomy and breast irradiation. In these women increased tissue density appeared on mammography only or disproportionately in the nonirradiated breast. To our knowledge, this observation has not been reported. CONCLUSION: Breast irradiation may induce tissue changes that prevent or diminish the proliferative response that can be induced in breast tissue by postmenopausal hormone replacement therapy. Because this treatment is now recommended for some women after breast conservation therapy, mammographers may recognize this finding with increasing frequency.     

Epithelial proliferation and hormone receptor status in the normal post-menopausal breast and the effects of hormone replacement therapy

The proliferation rate (as assessed by Ki67 expression) and expression of oestrogen-regulated progesterone receptor (PR) was studied in normal post-menopausal breast epithelium. Normal breast epithelium from patients receiving hormone replacement therapy (HRT) at the time of surgery containing either oestrogen alone (E2) or oestrogen and progesterone combined activities (E2 + P) was also studied, as HRT has been linked to an increased breast cancer risk. Samples of breast tissue, containing normal epithelium, from 185 patients undergoing surgery for benign or malignant disease were immunocytochemically stained for PR and Ki67. The percentage of labelled cells was expressed as the labelling index (LI). The median Ki67 LI in normal post-menopausal breast epithelium was 0.19 and median PR LI was 4.75, and both were unaffected by patient age, duration of menopause or if the tissue sample originated from a breast with benign or malignant disease. Proliferation did not alter significantly in patients taking HRT (P = 0.61); however, PR expression was up-regulated in both E2 and E2 + P users (P = 0.01). The dose and duration of HRT had no effect on either parameter. A possible attenuation of sensitivity to oestradiol-induced proliferation but not to PR expression occurs in the post-menopausal breast.     

Compliance considerations with hormone replacement therapy

Lactate accumulation, amino acid aspartate and glutamate levels, and hypoxanthine, xanthine and malondialdehyde (MDA) concentrations were compared in neonate rat brain after transient global hypoxia induced alone or in association with unilateral ligation of a carotid artery. Lactate production in both hemispheres was higher in cerebral hypoxia-ischemia (CHI) than in cerebral hypoxia (CH), and was lower in CHI after 2 h than at 15 min of recovery. Aspartate and glutamate levels were reduced 15 min after CHI in both hemispheres, but aspartate alone was decreased 2 h after CHI in the ipsilateral (left) hemisphere and 15 min after CH in both hemispheres. Hypoxanthine was increased 15 min after CHI in the ipsilateral hemisphere but decreased at 2 h, whereas xanthine was increased. MDA production was not modified after CH or CHI. These data, compared to those obtained in adult animals suggest that glutamate release and the capacity to generate oxygen-derived radicals are lower in neonates after ischemia. These differences might explain why the brain of the mammalian neonate is much more resistant to CH and CHI than that of the adult.     

Menopause and hormone replacement therapy

Menopause is a normal part of life of most women and can be made easier with appropriate information about the events that occur. For those women who desire help for bothersome menopausal symptoms, effective therapy can be offered. The use of HRT for prevention is more complex. Several large randomized clinical trials, including the Women's Health Initiative (WHI) and the Heart and Estrogen Replacement Therapy Study (HERS) in the United States, are currently underway. These trials, which have as end points clinical events such as myocardial infarction, sudden death, fractures, and cancer, will provide answers to many of the questions raised in this discussion. Until the results of these trials are available, clinicians must be prudent in their recommendations and should keep their patients apprised of the relevant uncertainties of preventive HRT.     

Effects of thyroid hormone replacement therapy on nocturnal apnea in elderly patients with hypothyroidism

BACKGROUND AND STUDY AIMS: Dieulafoy's disease is a rare cause of upper gastrointestinal tract hemorrhage. The aim of the study was to evaluate the efficacy of endoscopic hemostasis and to analyze the mortality of patients with hemorrhage due to Dieulafoy's disease. PATIENTS AND METHODS: The retrospective analysis included patients from our institution who had undergone urgent endoscopic examination of the upper digestive tract and hemostatic interventions in the period between January 1994 and December 1996. RESULTS: Twenty-five patients were examined (18 men and 7 women, average age 52.6, SD+/-15.3, range 25-78). In 20 patients endoscopic injection sclerotherapy was performed (diluted epinephrine 1:10,000 plus polidocanol 1%) and Nd:YAG laser photocoagulation in five patients. In all patients a total of 44 interventional endoscopies were carried out. Repeated endoscopic hemostasis did not prove successful in two patients (8%, 2 men), and they were treated operatively. During the postoperative period one patient died because of multiorgan failure. The total mortality rate of all patients in which endoscopic hemostasis was done was 16% (4/25). None of the 21 surviving patients had rebleeding on long-term follow-up (mean: 29.4 months). CONCLUSIONS: Endoscopic hemostasis is a major therapeutic advance in the management of Dieulafoy's disease hemorrhage. Interventional endoscopy has decreased the need for surgical management and significantly reduced mortality.     

Continuous combined hormone replacement therapy compared with tibolone

OBJECTIVE: To compare relief of vasomotor symptoms, changes in lipoproteins, and bleeding patterns in postmenopausal women receiving either continuous combined hormone replacement therapy (HRT) of estradiol valerate and norethisterone or tibolone 2.5 mg/day. METHODS: In a multicenter, randomized, open-label study, 235 postmenopausal women received one of the above-mentioned treatments. Fasting lipoproteins were measured at baseline and at 3, 6, and 12 months. At each visit, participants completed Greene climacteric questionnaires and recorded any bleeding episodes. Data are presented as mean +/- standard deviation if normally distributed, median and interquartile range if non-normally distributed, or as frequency count. For menopausal symptoms and diary card data, the differences were tested by Wilcoxon rank-sum test. RESULTS: One hundred sixteen women received continuous combined HRT and 119 women received tibolone; 72 and 76 women, respectively, completed 12 months of therapy. Both treatments effectively relieved vasomotor symptoms and reduced serum total cholesterol. Continuous combined HRT, but not tibolone, significantly reduced low-density lipoprotein levels. Both treatments reduced high-density lipoprotein levels, but the effect was more profound with tibolone. The initial bleeding score was higher for women taking continuous combined HRT; however, by the end of the study, the percentages of amenorrheal women were comparable. Endometrial histology was similar for both treatments at the end of the study, although two cases of proliferative endometrium were found in the tibolone group. CONCLUSION: Estradiol valerate-norethisterone continuous combined HRT controls symptoms and is associated with a safe lipid profile.     

Endometrial cytology in postmenopausal hormone replacement therapy

INTRODUCTION: The purpose was to examine whether health-promotion programs offered by California health plans are a serious attempt to improve health status or a marketing device used in an increasingly competitive marketplace. The research examined differences in the coverage, availability, utilization, and evaluation of health-promotion programs in California health plans. METHODS: A mail survey was done of the 35 HMOs (86% response) and 18 health insurance carriers (83% response) licensed to sell comprehensive health insurance in California in 1996 (some plans sell both HMO and PPO/indemnity products). The final sample included 30 commercial HMOs and 20 PPO and indemnity plans. The 1996 California Behavioral Risk Factor Survey (BRFS) of 4,000 adults was used to estimate population participation rates in health-promotion programs. RESULTS: California's HMOs in 1996 offered more comprehensive preventive benefits and health-promotion programs compared to PPO and indemnity plans. HMOs relied on a more comprehensive set of health-education methods to communicate health information to members and were more likely to open their programs to the public. HMOs are also more likely to have developed relationships with community-based and public health providers. Participation in health-promotion programs is low (2%-3%), regardless of plan type, and most health plans limit evaluations to assessment of member satisfaction and utilization. Only 35%-45% of HMOs, and no PPO/indemnity plans, assess the impact of health-promotion programs on health risks and behaviors, health status, or health care costs. CONCLUSION: For the majority of California's PPO and indemnity plans, health promotion is not an integral part of their business. For the majority of HMOs, health-promotion programs are offered primarily as a marketing vehicle. However, a substantial minority of HMOs offer health-promotion programs to achieve other organizational goals of health improvement and cost control.     

Quality-of-life changes in patients with thyroid cancer after withdrawal of thyroid hormone therapy

Quality of life (QOL) is an important consideration as patients survive longer with cancer and is an area of increasing interest in patients with thyroid cancer who undergo long-term cancer surveillance. However, there are few disease-specific QOL tools available to evaluate QOL in patients with thyroid cancer. The purposes of this longitudinal, repeated-measures study were to: (1) test a new instrument, the QOL-Thyroid Scale, during thyroid hormone withdrawal; and (2) to evaluate the impact of thyroid hormone withdrawal on patients' perceived changes in quality of life. The sample included 34 subjects (mean age 40 years) undergoing thyroid hormone withdrawal in preparation for scanning procedures. Subjects completed three instruments (demographic data tool, the QOL-Thyroid, and the FACT-G) at four specific time points in relationship to scanning. The results demonstrated that the QOL-Thyroid tool is a reliable and valid measure of QOL. Cronbach's alpha coefficient of r = .78 between QOL-Thyroid and FACT-G indicated good concurrent validity. Second, the impact of thyroid hormone withdrawal on QOL showed significant changes in physical, psychological, and social well-being across the four testing points. The greatest changes occurred between peak hormone withdrawal and thyroxine (T4) therapy. While it is generally known that patients suffer troublesome physical symptoms relating to thyroid hormone withdrawal, the negative psychological, family, and work sequelae are less apparent. In conclusion, the QOL-Thyroid is a reliable and valid measure for use in evaluating patients undergoing scanning procedures and may be used to identify and target teaching and support for high-risk areas in patients lives that are negatively affected by hormone withdrawal.     

The hormone replacement therapy self-efficacy scale

OBJECTIVE: Our purpose was to develop a specific polymerase chain reaction detection method for 16 micro-organisms in amniotic fluid and to correlate its performance with bacterial cultures and preterm delivery occurrence. STUDY DESIGN: The study group was made up of 50 patients with preterm labor and intact membranes. The control group consisted of 23 patients not in labor and undergoing amniocentesis for either karyotype or lung maturity studies. Polymerase chain reaction and bacterial cultures were assayed in amniotic fluid of all patients. Results were correlated with pregnancy outcome. RESULTS: Polymerase chain reaction identified micro-organisms in 23 cases in the study group (46%), whereas cultures identified only 6 (12%). All control samples were negative for polymerase chain reaction and cultures. The sensitivity of polymerase chain reaction and cultures for the identification of patients delivering before 34 weeks' gestation was 64% and 18%, respectively. CONCLUSION: A polymerase chain reaction gene amplification method was developed to identify 16 micro-organisms in amniotic fluid. Compared with bacterial cultures, polymerase chain reaction amplification in amniotic fluid appears to be more sensitive in identifying patients delivering prematurely.     

Educating patients about the benefits and drawbacks of hormone replacement therapy

Transthoracic Doppler echocardiography was used to evaluate the technique of measuring and normal patterns of pulmonary venous flow in fourteen normal dogs. Polyphasic pulmonary venous flow profiles were obtained in all dogs, consisting of one (S) or two (SE and SL) systolic forward flow waves, one early diastolic forward flow wave (D), one reverse flow wave (R) related to atrial contraction, and one reverse flow wave (R2) observed after cessation of systolic flow. Pulmonary venous flow was laminar in 9 dogs (65%). Maximal flow velocity during systole (0.39 +/- 0.14 m/sec) was significantly lower (P < 0.01) than in early diastole (0.56 +/- 0.14 m/sec). During late diastole peak flow velocity was 0.20 +/- 0.08 m/sec and maximum R2 velocity was 0.17 +/- 0.05 m/sec. Duration of mitral A-wave was significantly greater (P < 0.05) than R-wave duration in all dogs (0.075 +/- 0.010 vs 0.058 +/- 0.012 sec). These results can be used for comparison with patterns found in disease states.     

Sub-clinical worsening of bronchial asthma during estrogen replacement therapy in asthmatic post-menopausal women

BACKGROUND: Changes in asthma activity, in part related to the female hormonal profile, have been observed during pre-menstrual periods and during pregnancy. Estrogen replacement therapy (ERT) is an accepted routine treatment for post-menopausal women. The effect of ERT on disease activity in post-menopausal asthmatic women has not been investigated in the past and is the subject of the present study. METHODS: Fifteen post-menopausal women with mild to moderate asthma completed two 30-day periods in which they measured peak expiratory flow (PEF) at home and filled in a daily diary of asthma-related symptoms. The first monitoring period was pre-ERT and the second was during ERT. In addition spirometry was performed on each woman three times, twice pre-ERT and once during ERT. RESULTS: The average daily PEF decreased from 241 (57.9, S.D.) l/min pre-ERT to 226.7 (62.7) l/min during ERT (P < 0.004). Significant differences between the two study periods were also found in morning and evening PEF values. Diurnal variation, measured as the difference between morning and evening PEF values, decreased significantly from 22.3 (26.7) l/min pre-ERT to 17.5 (26.8) l/min during ERT (P < 0.007). The average daily consumption of bronchodilator inhalers increased significantly from 3.7 puffs/day pre-ERT to 4.3 puffs/day during ERT (P < 0.006). Although the differences in spirometry between the two periods did not reach statistical significance, a trend towards a worsening of the obstructive disorder during ERT was observed. However, the general feeling of well-being of the asthmatics did not change during the two periods. CONCLUSIONS: During ERT a sub-clinical worsening of disease activity was found in postmenopausal women with mild to moderate asthma. We also detected a decrease in diurnal variation. Our findings should be substantiated by additional studies.     

Sudden sensorineural deafness and hormone replacement therapy

Whilst the oral contraceptive pill (OC) has been implicated on a number of occasions as a cause of sensorineural hearing loss, there are no published reports linking hormone replacement therapy (HRT) to otological symptoms. A case of sensorineural loss with tinnitus following commencement of HRT is described, followed by a discussion outlining the fundamental differences between the OC and HRT, thus explaining why a vascular aetiology is unlikely. It is hypothesized that otological symptoms in such cases may be due to the effect of oestrogens on electrolyte balance disturbing inner ear function and also a direct effect on the auditory pathways mediated in part by alterations in neurotransmitter receptor concentrations.     

Postmenopausal hormone replacement therapy and cardiovascular disease

Cardiovascular disease is the leading cause of mortality in postmenopausal women in developed countries. A possible cardioprotective role of hormone replacement therapy (HRT) is suggested by epidemiologic studies of HRT and reduced risk of coronary heart disease, as well as by randomized trials of HRT and lipid subfractions. Estrogen has beneficial effects on the lipid profile, raising high-density lipoprotein cholesterol levels and reducing low-density lipoprotein cholesterol levels each by approximately 10%. Other possible biologic mechanisms include beneficial effects on vascular function, oxidative status, endothelial-dependent vasodilation, intimal hyperplasia and insulin sensitivity. Estrogen's net effects on coagulation and fibrinolysis are less clear. Estrogen replacement therapy is associated with decreased atherosclerosis in several animal models. However, most of the available data on HRT derive from observational studies or small randomized trials assessing biologic intermediates rather than clinical events. Further research, including large-scale randomized clinical trials, are required to evaluate definitively the role of estrogen replacement therapy, especially given uncertainties about the effects of combined estrogen-progestin therapy and the balance of benefits and risk of this common intervention in postmenopausal women.     

Cognitive changes during growth hormone replacement in adult men

Prostaglandins (PGs) lower intraocular pressure by increasing uveoscleral outflow, presumably via a receptor-mediated mechanism coupled to a second messenger pathway in the ciliary muscle. In the present study, we examined the effect of prostanoids on cyclic AMP production in cultured human ciliary muscle cells. Cells were identified based on their expression of smooth muscle specific alpha-actin and monoclonal antibody against desmin. Cyclic AMP production in confluent cells incubated with buffer solution containing various concentrations of prostanoids was analyzed by radioimmunoassay. PGE2 caused a time-dependent increase in cyclic AMP concentrations which reached a maximum after 10 mins. With the exception of PGD2, all prostanoids produced a concentration-dependent increase in cyclic AMP levels with the following rank order of activity: PGE2 > 11-deoxy-PGE1 > 16,16-dimethyl PGE2 > sulprostone > PGF2alpha. PGE2-induced increase on cyclic AMP levels was unaffected by AH6809, an antagonist at both PGD2 (DP) and E2 (EP1) receptors. Flurbiprofen decreased basal cyclic AMP concentrations suggesting that intramurally-generated PGs stimulate the formation of the nucleotide in ciliary smooth muscle cells. PGE2-induced increases in cyclic AMP production was synergistic with those induced by the diterpene activator of adenylyl cyclase, forskolin. We conclude that prostanoids active at EP2-receptors can stimulate cyclic AMP production in cultured human ciliary muscle cells.     

Adverse change in low-density lipoprotein subfractions profile with oestrogen-only hormone replacement therapy

In a prospective longitudinal study in 17 women, we investigated the effects of surgical menopause and subsequent oestrogen-only hormone replacement therapy (HRT) on plasma concentrations of total cholesterol, HDL cholesterol, LDL cholesterol, triglyceride and LDL subfractions profile. Plasma LDL is a heterogeneous population of particles of varying size, density and chemical composition. The predominance of small LDL particles is a newly-recognized risk factor for coronary artery disease. The LDL score is used to describe LDL subfractions profile and the greater the score, the higher the proportion of small LDL particles. Six weeks after hysterectomy and bilateral oopherectomy, total cholesterol and triglyceride concentrations were significantly increased (p < 0.01) as well as the LDL score (p < 0.05). After 6 weeks of oestrogen-only HRT, total cholesterol concentration was significantly lower and HDL cholesterol concentration significantly higher than before the treatment (p < 0.05). At the same time, mean LDL score significantly increased and in none of the women did LDL subfractions profile change favourably.     

Compliance with hormone replacement therapy in postmenopausal women. A comparative study

OBJECTIVE: To assess compliance with hormone replacement therapy in postmenopausal women. METHOD: Two groups were compared prospectively: 100 women who sought treatment for menopausal symptoms, and 82 women who had undergone a total abdominal hysterectomy with bilateral salpingo-oophorectomy and were using estrogen replacement therapy. RESULTS: Compliance rates after 6 months were 81.0% and 84.1% in the two groups, respectively, and after 12 months, 73.0% and 80.5%. CONCLUSIONS: The high rates are attributed to our investment in patient education of the benefits of treatment and repeated and close follow-up.