Long-term Use Of Hormone Replacement Therapy Research Articles

The effectiveness of estrogen therapy and aerobic exercise combined with resistance training therapy in postmenopausal womens osteoporosis

Postmenopausal osteoporosis (PMOP) usually happens five to ten years following a womans menopause, and some women over 50 in China suffer from PMOP. Hormone replacement therapy (HRT) and aerobics combined with resistance training are the two promising osteoporosis interventions, but few studies have compared their efficacy. The mechanisms by which exercise treatment and hormone replacement therapy affect bone mineral density (BMD) are examined in this review and other health parameters in postmenopausal osteoporosis patients. As studied in this paper, estrogen improves osteoporosis. However, risks such as venous thromboembolism limit the long-term use of HRT. In terms of exercise therapy, a direct comparison of aerobic exercise combined with resistance exercise and HRT showed that supervised exercise improved BMD more than HRT and that exercise also boosted metabolism and avoided the risks of HRT. In conclusion, aerobic and resistance training provides a safer alternative to HRT for managing postmenopausal osteoporosis, and further studies should optimize exercise regimens.

FORMULATION OF VAGINAL CREAM CONTAINING EXTRACTS OF LINUM USITATISSIMUM, FOENICULUM VULGARE, AND SALVIA OFFICINALIS FOR THE TREATMENT OF ATROPHIC VAGINITIS IN POSTMENOPAUSAL

Abstract Introduction: Postmenopausal women with atrophic vaginitis had thinner epithelium, a lower vaginal maturation index, and higher vaginal pH. We chose phytoestrogens as an alternate treatment for atrophic vaginitis because of the potentially substantial side effects of long-term hormone replacement therapy use documented in a large prospective trial. Materials and methods: In this research, Flax Seed, Foeniculum Vulgare, and Salvia officinalis were chosen as plants containing phytoestrogen. Three vaginal cream formulations (F1-F3) were prepared in this study. The physicochemical properties and stability of a vaginal lotion containing well-known phytoestrogen plants are investigated. This study evaluates Linum usitatissimum, Foeniculum vulgare seeds, and Salvia officinalis extract. Physical examination, stability, continuity, active ingredient release, and challenge test were the four key criteria for product evaluation. Results: The release test revealed that extracts from formulation 2 and formulation 3 were slower to release than formulation1. It is owing to F1’s decreased viscosity and F2 and F3’s higher hydrophilic properties. The polyethylene glycol in formulations F2 and F3 may increase the hydrophilicity of the formulation, resulting in a stronger inclination of hydrophilic flavonoid extracts to the base and a decrease in extract liberation from the formulation. The w/o nature of the formulations allows them to lubricate or moisturize the vaginal epithelium, reducing Atrophic vaginitis symptoms. Conclusion: Formulation 1 may be a viable alternative to the current treatments for atrophic vaginitis. To determine the efficacy of this herbal vaginal cream in treating the symptoms of atrophic vaginitis, however, additional scientific studies are necessary.

Association Between Hormone Replacement Therapy and Development of Endometrial Cancer: Results From a Prospective US Cohort Study.

Although hormone replacement therapy (HRT) use is associated with elevated endometrial cancer(EC) risk, little evidence assesses potential effect-modifiers on HRT-related EC in a long-term follow-up. In this large-scale longitudinal cohort study, we tried to evaluate the association between different HRT types/methods use and risk of EC, and reveal this risk within different body mass index (BMI) groups. In whole cohort, 677 EC occurred during mean 11.6 years follow-up. Cox proportional hazards regression was used to estimate multivariable-adjusted hazards ratios (HRs) and 95% confidence intervals (CIs) with HRT status (never, former, or current) for risk of EC incidence. Current HRT use was not significantly associated with EC risk (HR for current vs. never HRT use: 1.13; 95% CI: 0.92, 1.38) in the whole cohort, but presented a dose-response effect on increased EC risk (HR for >10-year use vs. never HRT use: 1.73; 95% CI: 1.35, 2.21). Moreover, EC risk differed in distinct regimens or subsets (all Pinteraction < 0.05). Estrogen-only use was associated with elevated EC risk (HR for current vs. never HRT use: 1.51; 95% CI: 1.12, 2.04), but women with high BMI (> 30 kg/m2) who currently use estrogen-only harbored decreased EC risk (HR: 0.56; 95% CI: 0.38, 0.82) compared to counterparts without HRT use. Estrogen-only use is associated with increased EC risk, and precise monitoring of EC development for postmenopausal women with long-term HRT use are urgently needed. BMI could serve as an important surrogate to assess this risk.

Hormone Therapy and Risk of Breast Cancer: Where Are We Now?

Several studies have examined the clinical benefits of hormone replacement therapy (HRT). However, because long-term use of HRT has been implicated as a risk factor for the development of breast cancer, some women remain skeptical when considering this therapy to address their vasomotor symptoms. Hence, physicians and nurses should actively engage in constructive discourse with their patients regarding HRT while specifically reviewing the potential risks of its extended use as well as provide the available medical alternatives the patients could potentially use.

Long-term Use of Hormone Replacement Therapy is Associated With a Lower Risk of Developing High-risk Serrated Polyps in Women.

Hormone replacement therapy (HRT) and parity have been suggested protective factors against the development of colorectal polyps. However, there are a limited number of studies that have examined the relationship of these factors with high-risk adenomatous polyps (HRAP) or high-risk serrated polyps (HRSP), which may have different causes and therefore implications for screening programs. Data from a cross-sectional study of 1384 women undergoing screening-related colonoscopy between 2008 and 2016 were analyzed. Modified Poisson regression models with robust error variance were used to determine the relative risk of developing adenomatous polyps, serrated polyps, HRAPs, and HRSPs associated with pregnancy, menopausal status, and the use of HRT (duration and type). Women that used HRT for ≥6 years were at a significantly lower risk of developing a HRSP [risk ratios (RR): 0.53; 95% confidence interval (CI): 0.29-0.97]. Irrespective of the duration of use, the use of HRT that included progesterone alone or with estrogen was associated with a significantly lower risk of developing a HRSP (RR: 0.54; 95% CI: 0.30-0.95). The use HRT with progesterone for ≥6 years was associated with a nonsignificant lower risk of developing a HRSP (RR: 0.42; 95% CI: 0.17-1.04). None of the reproductive factors assessed or HRT were associated with the development of adenomatous polyps or HRAPs. The results of this study suggests that the long-term use of HRT, and therapies that include progesterone are associated with a lower risk of developing HRSPs. These results could have implications for targeted screening for serrated polyps among women.

Effects of hormone replacement therapy on lens opacity, serum inflammatory cytokines, and antioxidant levels

Purpose To evaluate the effect of hormone replacement therapy (HRT) on lens opacity as measured by Scheimpflug densitometry, serum inflammatory cytokines, and antioxidant levels. Methods A total of 264 women who were at least five years beyond menopause were included. The control group of 128 patients (Group 1) did not use HRT at any time after menopause. The treatment group of 136 patients (Group 2) used HRT for5 years or more after menopause. Cortical, nuclear, and posterior subcapsular density; pentacam nucleus staging (PNS); pentacam densitometry of zone (PDZ) as measured using a Scheimpflug imaging system (Pentacam); and antioxidant and inflammatory cytokines activities in serum using multiplex bead analysiswere examined. Results Uncorrected visual acuity (logMAR) of group1 was significantly worse than those of group 2 (p < .05). Group1 was significantly more myopic than group 2 (p < .05). Nuclear and posterior subcapsular density, PNS, and percentage of PDZ in group 1 were significantly higher than those of group 2 (p < .05). The serum IL-1m. IL-6, IL-8, and TGF-, concentrations of group 1 were significantly higher than those of group 2, and the serum catalase, superoxide dismutase 1 (SOD 1), and superoxide dismutase 2 (SOD 2) fluorescence intensities of group 1 were significantly lower than those of group 2 (p < .05). Conclusions Long-term use of HRT may have a protective effect against cataract formation. HRT seems to be effective in decreasing inflammation and increasing antioxidant contents in the serum of postmenopausal women. KEY MESSAGES Hormone replacement therapy (HRT) decrease lens opacity in postmenopausal women as measured by Scheimpflug densitometry. HRT decrease serum inflammatory cytokines and increase antioxidant levelsin the serum of postmenopausal women. Long-term use of HRT may have a protective effect against cataract formationin postmenopausal women.

Hormone replacement therapy enhances IGF-1 signaling in skeletal muscle by diminishing miR-182 and miR-223 expressions: a study on postmenopausal monozygotic twin pairs.

MiRNAs are fine-tuning modifiers of skeletal muscle regulation, but knowledge of their hormonal control is lacking. We used a co-twin case–control study design, that is, monozygotic postmenopausal twin pairs discordant for estrogen-based hormone replacement therapy (HRT) to explore estrogen-dependent skeletal muscle regulation via miRNAs. MiRNA profiles were determined from vastus lateralis muscle of nine healthy 54–62-years-old monozygotic female twin pairs discordant for HRT (median 7 years). MCF-7 cells, human myoblast cultures and mouse muscle experiments were used to confirm estrogen’s causal role on the expression of specific miRNAs, their target mRNAs and proteins and finally the activation of related signaling pathway. Of the 230 miRNAs expressed at detectable levels in muscle samples, qPCR confirmed significantly lower miR-182, miR-223 and miR-142-3p expressions in HRT using than in their nonusing co-twins. Insulin/IGF-1 signaling emerged one common pathway targeted by these miRNAs. IGF-1R and FOXO3A mRNA and protein were more abundantly expressed in muscle samples of HRT users than nonusers. In vitro assays confirmed effective targeting of miR-182 and miR-223 on IGF-1R and FOXO3A mRNA as well as a dose-dependent miR-182 and miR-223 down-regulations concomitantly with up-regulation of FOXO3A and IGF-1R expression. Novel finding is the postmenopausal HRT-reduced miRs-182, miR-223 and miR-142-3p expression in female skeletal muscle. The observed miRNA-mediated enhancement of the target genes’ IGF-1R and FOXO3A expression as well as the activation of insulin/IGF-1 pathway signaling via phosphorylation of AKT and mTOR is an important mechanism for positive estrogen impact on skeletal muscle of postmenopausal women.

Hormone replacement therapy increases the risk of cranial meningioma

AimWe investigated the influence of hormone replacement therapy (HRT) use on the risk of meningioma in a population-based setting. MethodsWe conducted a nationwide case–control study in Denmark based on population-based administrative and health registries. The study included all female patients aged 55–84years with a first time diagnosis of meningioma during 2000–2009. The cases were matched on birth year with female population controls. Ever use of HRT since 1995 was defined as ⩾2 HRT prescriptions and categorised according to HRT type (oestrogen only, combined oestrogen–progestagen, and progestagen only) and cumulated duration of use (<1, ⩾1 to <5, ⩾5 to <10, ⩾10years). We used conditional logistic regression to compute odds ratios (ORs), with 95% confidence intervals (CIs), for meningioma associated with HRT use, and adjusting for potential confounders. ResultsWe identified 924 cases and 6122 controls. Ever use of HRT was associated with an increased risk of meningioma (OR, 1.3; 95%CI, 1.1–1.5) compared with non-use (0–1 prescriptions). The risk increased with increasing duration of HRT use, reaching an OR of 1.7 (95% CI, 1.2–2.3) after more than 10years of use. The risk of meningioma associated with long-term (⩾10years) HRT use was most pronounced for combined oestrogen–progestagen therapy (OR, 2.2; 95% CI, 1.4–3.3), especially when this regimen constituted the sole HRT therapy (OR, 2.7; 95% CI, 0.9–7.5), although the latter estimate was based on small numbers. ConclusionsLong-term HRT use, particularly of combined oestrogen–progestagen therapy, may increase the risk of meningioma.

Confirmation of the reduction of hormone replacement therapy-related breast cancer risk for carriers of the HSD17B1_937_G variant

17β-hydroxysteroid dehydrogenase type 1 (HSD17B1) plays an important role in the biosynthesis of 17β-estradiol. The current study aimed at confirming the reduced risk of breast cancer in carriers of the non-synonymous HSD17B1_937_A>G (rs605059) polymorphism who used any hormone replacement therapy (HRT) for 10years or longer. We performed an independent association study using four breast cancer case-control studies from Australia, Germany, and Sweden. In all, 5,777 cases and 8,189 age-matched controls of European descent were genotyped by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and TaqMan. Risk estimates were calculated by interaction analysis and main effect analysis adjusted for age and study. Main effect analyses for women using any HRT for 10years or longer (1,428 cases versus 1,724 controls) revealed a protective effect of the HSD17B1_937_G allele on breast cancer risk (OR 0.86, 95% CI: 0.73-0.99; p=0.048). Thus, our previous finding of a protective effect of the HSD17B1_937_G allele on HRT-associated breast cancer risk has now been confirmed both in independent large patient cohorts and a comprehensive pooled analysis supporting the hypothesis that a HSD17B1-mediated decreased conversion of estrone to the more potent 17β-estradiol may reduce the estrogenic effects, thereby reducing the risk of developing breast cancer during long-term HRT use.

Estrogen metabolism genotypes, use of long-term hormone replacement therapy and risk of postmenopausal breast cancer

Association between long-term hormone replacement therapy (HRT) use and increased risk of breast cancer is still under debate. Functionally relevant genetic variants within the estrogen metabolic pathway may alter exposure to exogenous sex hormones and affect the risk of postmenopausal breast cancer. We investigated the associations of common polymorphisms in 4 genes encoding key proteins of the estrogen metabolic pathway, duration of HRT use and their interactions with breast cancer risk. We studied 530 breast cancer cases and 270 controls of the same age and ethnicity participating in a case-control study of postmenopausal women. Duration of HRT use was ascertained through a postal questionnaire. Genotyping was conducted for CYP1B1 (rs1056836), COMT (rs4680), GSTP1 (rs1695) and MnSOD (rs4880) polymorphisms by PCR-based RFLP and TaqMan® allelic discrimination method. Adjusted odds ratios and 95% confidence intervals were calculated using logistic regression analysis. HRT use was significantly associated with decreased breast cancer risk (p<0.001). None of the polymorphisms studied was associated with breast cancer risk. A significant interaction was observed between MnSOD 47T>C and HRT use (pinteraction=0.036); the risk of breast cancer associated with long-term vs. short-term HRT use was decreased in women homozygous for the wild-type allele and increased in women with at least one variant allele of the MnSOD 47T>C polymorphism. Our results suggest that MnSOD 47T>C polymorphism in interaction with long-term HRT use may modify the risk of breast cancer.

The Influence of Estrogen on Skeletal Muscle

As women enter menopause, the concentration of estrogen and other female hormones declines. This hormonal decrease has been associated with a number of negative outcomes, including a greater incidence of injury as well as a delay in recovery from these injuries. Over the past two decades, our understanding of the protective effects of estrogen against various types of injury and disease states has grown immensely. In skeletal muscle, studies with animals have demonstrated that sex and estrogen may potentially influence muscle contractile properties and attenuate indices of post-exercise muscle damage, including the release of creatine kinase into the bloodstream and activity of the intramuscular lysosomal acid hydrolase, beta-glucuronidase. Furthermore, numerous studies have revealed an estrogen-mediated attenuation of infiltration of inflammatory cells such as neutrophils and macrophages into the skeletal muscles of rats following exercise or injury. Estrogen has also been shown to play a significant role in stimulating muscle repair and regenerative processes, including the activation and proliferation of satellite cells. Although the mechanisms by which estrogen exerts its influence upon indices of skeletal muscle damage, inflammation and repair have not been fully elucidated, it is thought that estrogen may potentially exert its protective effects by: (i) acting as an antioxidant, thus limiting oxidative damage; (ii) acting as a membrane stabilizer by intercalating within membrane phospholipids; and (iii) binding to estrogen receptors, thus governing the regulation of a number of downstream genes and molecular targets. In contrast to animal studies, studies with humans have not as clearly delineated an effect of estrogen on muscle contractile function or on indices of post-exercise muscle damage and inflammation. These inconsistencies have been attributed to a number of factors, including age and fitness level of subjects, the type and intensity of exercise protocols, and a focus on sex differences that typically involve factors and hormones in addition to estrogen. In recent years, hormone replacement therapy (HRT) or estrogen combined with exercise have been proposed as potentially therapeutic agents for postmenopausal women, as these agents may potentially limit muscle damage and inflammation and stimulate repair in this population. While the benefits and potential health risks of long-term HRT use have been widely debated, controlled studies using short-term HRT or other estrogen agonists may provide future new and valuable insights into understanding the effects of estrogen on skeletal muscle, and greatly benefit the aging female population. Recent studies with older females have begun to demonstrate their benefits.

Malignant transformation of residual endometriosis after hysterectomy: a case series

To explore the role of long-standing hormone replacement therapy (HRT) in the malignant transformation of endometriosis. Short case series. Three cases of women with pelvic clearance receiving long-standing HRT studied in detail. Teaching hospital in the United Kingdom (Gynaecological Cancer Centre) (Institutional Review Board approval was not obtained as it was not deemed necessary, this being a case series). Women with a history of pelvic clearance for endometriosis and longstanding HRT. HRT. Malignant transformation of endometriosis. Long-standing HRT in all three women with pelvic clearance for endometriosis resulted in malignant transformation of residual endometriosis many years after the initial surgery. All cases presented with a new pelvic lesion. The diagnosis of malignant transformation needs to be considered in women with a history of endometriosis and with long-term HRT use in whom a new pelvic lesion is detected. The risk of malignant transformation in women with endometriosis after pelvic clearance receiving HRT needs to be explored further. Surveillance with CA-125 and imaging in such cases to predict recurrence or malignant transformation needs to be studied further in a research setting.

Estrogen-biosynthesis gene CYP17 and its interactions with reproductive, hormonal and lifestyle factors in breast cancer risk: results from the Long Island Breast Cancer Study Project

The genes that are involved in estrogen biosynthesis, cellular binding and metabolism may contribute to breast cancer susceptibility. We examined the effect of the CYP17 promoter T --> C polymorphism and its interactions with the reproductive history, exogenous hormone use and selected lifestyle risk factors on breast cancer risk among 1037 population-based incident cases and 1096 population-based controls in the Long Island Breast Cancer Study Project. Overall, there were no associations between the CYP17 genotype and breast cancer risk. Among postmenopausal women, the joint exposure to higher body mass index (BMI) and the variant C allele was associated with an increased risk of breast cancer [odds ratio (OR), 1.60; 95% confidence interval (CI), 1.15-2.22]. The joint exposure to the variant C allele and long-term use of hormone replacement therapy (HRT) (>51 months) was related to an increased risk of breast cancer (OR, 1.51; 95% CI, 0.99-2.31) especially estrogen receptor-positive, progesterone receptor-positive breast cancer (OR, 1.87; 95% CI, 1.08-3.25). Among the control population, the CYP17 variant C allele was inversely associated with long-term use of postmenopausal HRT and a higher BMI in postmenopausal women. In conclusion, the findings suggest that the CYP17 variant C allele may increase breast cancer risk in conjunction with long-term HRT use and high BMI in postmenopausal women.

Menopause hormone replacement therapy and cancer risk: an Italian record linkage investigation

BackgroundThe effects of persistence with hormone replacement therapy (HRT) on the risk of hospitalization for cancer and of the route of HRT administration on the risk of breast and colorectal cancer were explored in a large cohort study. Patients and methodsThe 73505 women residing in Lombardia (Italy), aged 45–75 years, who received at least one HRT prescription during 1998–2000 were followed until 2005. Among these, 3687 experienced cancer hospitalization. Proportional hazards model was fitted to estimate the association between cumulative HRT persistence and cancer risk. ResultsCompared with women who took HRT for <6 months, those exposed for >2 years showed hazard ratios (HR) of 0.78 (95% confidence interval 0.68–0.92) for colorectal cancer and 1.34 (1.13–1.58) for breast cancer. HR for breast cancer associated with long-term use of transdermal and oral HRT were, respectively, 1.27 (1.07–1.51) and 2.14 (1.43–3.21). ConclusionsEvidence that long-term use of HRT is associated with increased risk of breast cancer and decreased risk of colorectal cancer is supplied from this study from a southern European population. Our findings indicate that transdermal therapy might have lower effect than oral therapy in increasing breast cancer risk.

Age and Menopausal Effects of Hormonal Birth Control and Hormone Replacement Therapy in Relation to Breast Cancer Risk

It is unclear whether breast cancer risk varies by age and menopausal status in relation to use of hormonal birth control (HBC) and hormone replacement therapy (HRT), taken singly or cumulatively. The authors utilized data from 1,478 cases and 1,493 controls aged 20-98 years with known menopausal status, who had participated in a population-based, case-control study conducted on Long Island during 1996-1997. Exogenous hormone use over the lifecourse was assessed by use of memory aids. The authors examined associations among women in these subgroups: premenopausal (n = 968), postmenopausal <65 years (n = 1,045), and postmenopausal > or = 65 years (n = 958). Among premenopausal women, risk was increased for ever use of HBC (odds ratio (OR) = 1.37, 95% confidence interval (CI): 1.04, 1.81) or HRT (OR = 1.81, 95% CI: 1.17, 2.81) and was pronounced among women reporting use of both HBC and HRT (OR = 2.59, 95% CI: 1.50, 4.46), long-term HRT use (OR = 3.93, 95% CI: 1.43, 10.84), or estrogen-plus-progestin therapy (OR = 3.51, 95% CI: 1.45, 8.49). There was no effect of ever HBC use among postmenopausal women aged less than 65 years, but risk was modestly elevated for more than 5 years of HRT use (OR = 1.41, 95% CI: 1.00, 1.99). Among postmenopausal women aged 65 years or more, odds ratios for HBC or HRT use were around the null. These results emphasize that timing of exogenous hormone use is important. Women who used these hormones before menopause had elevated risks, but the harmful effects began to decline with age after menopause.

Menopause, mild psychological stress and salivary cortisol: Influence of long-term hormone replacement therapy (HRT)

Objective Aim of the present study was to examine the adrenocortical activity in basal condition and following a mild stress exposure in long-term HRT-treated menopausal women. Menopausal women, long term users of HRT (14 subjects) were compared both to menopausal women who had never used HRT (14 subjects) and young pre-menopausal women (14 subjects). Study design Morning and evening salivary cortisol secretion was measured in samples collected twice a day (08:00 in the morning and 08:00 in the evening). Mild stress response was evoked by administration of the Stroop color-word test (CWT). Salivary cortisol was measured immediately before the start, 15, 30 and 45 min after the completion of the test. Results Menopause appears not to be associated with an impairment of cortisol circadian fluctuation. Long-term use of HRT in menopause attenuated HPA activity either in basal condition or in response to mild stress exposure. With regard to the CWT performance, all menopausal women took significantly longer than young women to perform the test. However, long-term HRT significantly reduced the number of errors made during the test. Conclusions The present study suggested that long-term HRT could help menopausal patients to cope with mild stress and to improve mental performances.

Immune responses and bone loss: the estrogen connection

In addition to its effects on sexual differentiation and reproduction, estrogen has important impact on the immune system and on bone. It has also been evident that the effects of estrogen on bone to a large extent are mediated via its action on immune cells. Estrogen has a dichotomous impact on the immune system by downregulation of inflammatory immune responses but simultaneous upregulation of immunoglobulin production. Consequently, immune-mediated diseases in humans and in animal models are modulated by estrogen. Estrogen deficiency after ovariectomy in mice and after menopause in women is associated with significant bone loss. In rheumatic diseases such as rheumatoid arthritis (RA), osteoporosis is frequent, and in patients with postmenopausal RA, the degree of bone loss is dramatically increased. Hormone replacement therapy (HRT) in murine and human arthritis has beneficial effects on bone loss, as expected, but it also ameliorates inflammation and inflammation-triggered joint destruction. Long-term use of HRT has been associated with increased risk of breast cancer, thrombosis, and possibly also stroke. Accordingly, there is great need for new activators of estrogen receptors (ERs) selectively reproducing only the beneficial effects of estrogen. To achieve this aim, better knowledge of the mechanisms of how activation of ER-alpha and ER-beta modulates the immune system and bone at the cellular and molecular levels is necessary.

Factors Modifying the Association Between Hormone-Replacement Therapy and Breast Cancer Risk

Hormone-replacement therapy (HRT) is an established risk factor for breast cancer. HRT users are different from non-users with respect to socio-economic and other characteristics. There may be women where the HRT-related risk could be modulated by other factors. We conducted a population-based case-control study with 688 breast cancer cases and 724 controls to characterize HRT users and to estimate odds ratios (OR) and 95% confidence intervals (CI) for HRT use and potentially risk modifying factors. In women aged 50 years and older, 58% of controls and 61% of cases ever used HRT. Among women in natural menopause, HRT use for 10 years and more years was associated with an increased breast cancer risk (OR 1.79, 95% CI, 1.12-2.87), but not among women in surgical menopause (OR 0.61, 95% CI, 0.09-4.17). In the subgroup of women with a positive family history of breast cancer, each year of HRT use increased the risk by 1.22 (95% CI, 1.02-1.47). Another subgroup comprised women with at least 10 diagnostic mammograms (OR 4.04, 95% CI, 1.10-14.81 for using HRT 10 or more years). Long-term HRT use was associated with a breast cancer risk in women with natural menopause. Our findings suggest that this risk may be increased in women with a positive family history of breast cancer and in women who received frequent diagnostic mammographic screens.

Literature review of instruments to assess health-related quality of life during and after menopause

Menopause is a physiological event occurring in women at about the age of 50. It signals the end of the reproductive years and is associated with signs of estrogen deficiency having a considerable impact on women's health-related quality of life (HRQoL). The most common form of treatment is hormone replacement therapy (HRT). Studies have shown negative events can arise from long-term use of HRT. The aim of this review is to determine if there are any HRQoL instruments that address the impact of menopausal symptoms including positive and negative effects of HRT. The following eight instruments were identified: Greene Climacteric Scale, Women's Health Questionnaire (WHQ), Qualifemme, Menopause-Specific QOL Questionnaire (MENQOL), Menopausal Symptoms List (MSL), Menopause Rating Scale (MRS), Menopausal Quality of Life Scale (MQOL), and the Utian Quality of Life Scale (UQOL). All instruments reviewed proved to be reasonably structured and have their place in applied research. None were found that addressed all aspects of the impact of HRT on HRQoL. In order to capture the possible short-term side effects of HRT on HRQoL, it is necessary to modify one or more of the existing instruments or develop a new instrument applicable in many different countries and languages.

Two to three years of hormone replacement treatment in healthy women have long-term preventive effects on bone mass and osteoporotic fractures: the PERF study

Hormone replacement therapy (HRT) is often prescribed for a few years to suppress menopausal symptoms. Although its long-term use of HRT for the primary prevention of osteoporosis is not currently recommended, the long-term skeletal benefits of the limited therapy are of great interest. To determine whether administration of HRT for 2–3 years in the early postmenopausal years provides long-term benefits, such as prevention of bone loss and osteoporotic fractures, we studied a group of 347 healthy postmenopausal women with normal bone mass who had earlier completed one of four placebo-controlled HRT trials and who were reexamined 5, 11, or 15 years after stopping HRT. Of these women, 263 received either HRT or placebo for 2–3 years with no further bone-sparing treatment until follow-up, and the remaining 84 women reported either prolonged or current use of HRT at reexamination. Bone mineral density (BMD) at the spine (L1–L4) and bone mineral content (BMC) in the forearm were measured at baseline, the end of the trials, and follow-up. At follow-up, we assessed the radiological presence of vertebral fracture and collected information on the new incidence of nonvertebral fractures. Compared with that of the placebo-treated women, the BMD and BMC of HRT-treated women continued to show significantly higher values (>5%) even many years after stopping HRT. After stopping treatment, the rate of bone loss returned to normal postmenopausal rates. The preservation of bone mass in the HRT group was accompanied by a significantly reduced risk of all osteoporotic fractures as compared with the placebo group [OR = 0.48 (95% CI, 0.26–0.88)]. ‘Fast losers’ on placebo had more than a 4-fold higher risk of fractures than had the women on limited HRT with a normal rate of bone loss after withdrawal. In conclusion, limited HRT administered in the early postmenopausal years offers long-lasting benefits for the prevention of postmenopausal bone loss and osteoporotic fracture.