Initiation Of Estrogen Replacement Therapy Research Articles

Skeletal Characteristics of Children and Adolescents with Turner Syndrome

Turner syndrome (TS) is a chromosomal disorder characterized by a short stature and gonadal dysgenesis, the latter of which requires estrogen replacement therapy (ERT) to induce and maintain secondary sexual characteristics. Insufficient ERT is associated with compromised skeletal health, including bone fragility, in adults with TS. In particular, estrogen insufficiency during adolescence is critical because the acquisition of a defective bone mass during this period results in impaired bone strength later in the life. In addition to bone mass, bone geometry is also a crucial factor influencing bone strength; therefore, a more detailed understanding of the skeletal characteristics of both bone mass and geometry during childhood and adolescence and their relationships with the estrogen status is needed to prevent compromised skeletal health during adulthood in TS. Although a delay in the initiation of ERT is associated with a lower bone mineral density during adulthood, limited information is currently available on the effects of ERT during adolescence on bone geometry. Herein, we summarize the current knowledge on skeletal characteristics in children and adolescents with TS and their relationships with estrogen sufficiency, and discuss the potential limitations of the current protocol for ERT during adolescence in order to achieve better skeletal health in adulthood.

Trends in use of estrogen replacement therapy for premenopausal women with gynecologic cancer after surgical menopause (372)

<b>Objectives:</b> Estrogen replacement therapy (ERT) for pre-menopau- sal women who undergo oophorectomy and surgical menopause with gynecologic cancers remains controversial. ERT may not only prevent menopausal symptoms but also decrease the risk of longterm sequelae of estrogen deprivation, including osteoporosis and cardiovascular disease. We examined trends in the use of ERT among pre-menopausal women with gynecologic cancer who underwent bilateral oophorectomy. <b>Methods:</b> The IBM Watson Health MarketScan Database was used to identify women <50 years of age with gynecologic cancer who underwent bilateral salpingo-oophorectomy (BSO) from 2008-2019. ERT was defined as any prescription of estrogen with or without progesterone filled from six weeks prior to BSO to within three years of BSO. The cumulative rates of ERT use over time, time to initiation of ERT, and duration of ERT were examined. Performance of testing associated with estrogen deprivation in young women, including bone mineral density testing, lipid screening, and diabetes screening, was examined. Cumulative rates of ERT stratified by age groups were analyzed using Kaplan-Meier analyses. A multivariable log-linear regression model was developed to examine factors associated with ERT use. <b>Results:</b> A total of 4,972 women were identified. Overall, 1,952 (38.5%) women received ERT and 3,060 (61.5%) were not treated with ERT. The rate of ERT declined year over year from a peak of 45.9% in 2008 to 17.7% in 2019. Patients aged 18-29 years had the highest rate of ERT (62.9%) use, and those aged 45-50 years had the lowest rate (31.7%). The median time to initiation of ERT was 0.4 months after BSO (IQR: 0.1-2.5 months), and ERT was used for a median of 3.4 months (IQR: 1.0-10.3 months). The cumulative rate of ERT use at 12, 24, 36 months after BSO was 36.3%, 38.9%, and 40.3%, respectively. ERT was utilized in 30.4% of women with uterine cancer, 55.7% of women with cervical cancer, and 34.3% with ovarian cancer. In a multivariable model, younger age, Medicaid recipient, concurrent hysterectomy with BSO, and diagnosis of cervical cancer were associated with higher ERT rates. By the end of 36 months of BSO, bone mineral density testing was performed in 16.6% of women who received ERT compared to 16.9% not treated with ERT, while lipid testing was performed in 70.7% and 73.0% of women in these groups, respectively. Fig. 1 <b>Conclusions:</b> The rate of ERT after surgical menopause among premenopausal women with gynecologic malignancies has declined substantially. Testing for adverse events associated with estrogen deprivation is uncommon.

Effects of age at estrogen replacement therapy initiation on trabecular bone score in Japanese adults with Turner syndrome.

Studies have reported associations between bone mineral density and estrogen replacement therapy (ERT) in Turner syndrome (TS) patients; however, few studies exist on the effect on bone quality. The aim of this study was to evaluate the effects of the age at ERT initiation on bone quality of Japanese TS patients, cross-sectionally and longitudinally. Cross-sectionally, 95 TS patients were divided into three groups based on their age at initiation of ERT: A (12-14 years, 11 patients), B (15-17 years, 47 patients), and C (over 18 years, 37 patients). To assess bone quality, trabecular bone score (TBS) was used. The effects of age at initiation and duration of ERT on TBS were examined using multiple regression analysis. In the longitudinal study, 48 patients who underwent dual-energy X-ray absorptiometry multiple times were divided into three groups: D (12-14 years, 8 patients), E (15-17 years, 18 patients), and F (over 18 years, 22 patients). Each group was analyzed for the rate of change in TBS per year. Cross-sectionally, the TBS showed significant differences among the three groups (TBS A, 1.302; B, 1.299; C, 1.245) (p = 0.013); group C was significantly lower than B (p = 0.014); bone quality was degraded. Multiple regression analysis revealed that age at ERT initiation significantly affected the increase in TBS (p = 0.002). Longitudinally, the rate of change of TBS was not significantly different in the three groups (p = 0.73). Early initiation of ERT may have positive effects on bone quality in TS. Large prospective studies will be needed.

Late-Onset Puberty Induction by Transdermal Estrogen in Turner Syndrome Girls-A Longitudinal Study.

Estrogen replacement therapy (ERT) for Turner syndrome (TS) is a widely discussed topic; however, the optimal model of ERT for patients with delayed diagnosis and/or initiation of therapy is still unclear, mainly due to insufficient data. We present the results of a prospective observational single-center study in which the efficacy of late-onset puberty induction by one-regimen transdermal ERT in TS girls was evaluated. The analysis encompassed 49 TS girls (63.3% with 45,X) with hypergonadotropic hypogonadism in whom unified transdermal ERT protocol was used for puberty induction (first two months 12.5 μg/24 h, thereafter 25.0 μg/24 h until breakthrough bleeding). Clinical visits for examination and therapy modification took place every 3-6 months. Transabdominal pelvic ultrasound examinations were performed at least twice: at the beginning and at the end of follow-up. The mean (SD) age at ERT induction was 15.1 (1.3) years. The duration of follow-up was 2.4 (1.1) years. Half of all the patients had at least B2 after 0.57 years, B3 after 1.1 years, B4 after 1.97 years, and menarche after 1.82 years from ERT initiation. With earlier initiation of ERT (≤14 years), B2 (p = 0.059) was achieved faster and B4 (p = 0.018) significantly slower than with the later start of ERT. Thirty-four (94.4%) patients had at least stage B3 at menarche. The karyotype, initial weight, and body mass index had no impact on puberty tempo during ERT. The uterine volume increased significantly during ERT in all the study group (p < 0.0001), and in half of the patients, the increase was at least 12.4-fold. It did not correlate with the duration of treatment (p = 0.84) or the dose of estradiol per kilogram (p = 0.78), nor did it depend on karyotype (p = 0.71) or age at ERT initiation (p = 0.28). There were no differences in ΔhSDS during ERT (p = 0.63) between the two age groups (ERT ≤14 and >14 years). The presented easy-to-use fixed-dose regimen for late-onset puberty induction allowed for a satisfactory rate of achieving subsequent puberty stages and did not influence the growth potential.

Efficacy of estrogen replacement therapy (ERT) on uterine growth and acquisition of bone mass in patients with Turner syndrome.

Estrogen replacement therapy (ERT) is necessary for uterine development and bone mass acquisition in women with Turner syndrome (TS) suffering from ovarian insufficiency. However, adequate ERT regimens have not yet been established. The aim of this study was to evaluate the efficacy of ERT for both uterine development and bone mass acquisition. One hundred TS patients from Yokohama City University Hospital (88 with primary amenorrhea (PA) and 12 patients with spontaneous menstrual cycles (MC)) were enrolled after obtaining consent. Clinical profiles, uterine length (UL) measured by ultrasonic examination, and bone mineral density (BMD) of the lumbar vertebrae (L2-4) assessed by DEXA were evaluated. At the time of the first visit, the ULs of patients in the PA group were significantly shorter than those in the MC group. After receiving ERT, there were no significant differences in UL between patients with PA and MC. Forty-seven patients for whom the ERT initiation age was known were investigated to clarify the influence on BMD. The results showed that the BMD in the late initiation (18 years or older) group at the latest visit (0.770 ± 0.107 g/cm2: n = 16) was significantly lower than that in the early initiation (under 18 years) group (0.858 ± 0.119 g/cm2: n = 21) or the MC group (0.941 ± 0.118 g/cm2: n = 10). No significant differences were seen between the early initiation and MC group. ERT was effective in increasing UL and BMD. However, early initiation of ERT is necessary to increase BMD.

Physiological Estrogen Replacement Therapy for Puberty Induction in Girls: A Clinical Observational Study

Background/Aim: The goal of estrogen replacement therapy (ERT) in girls with hypogonadism is to achieve the endocrine milieu similar to natural puberty, where transdermal administration is the most physiological route. The aim of the study was to evaluate guidelines for the induction of puberty with transdermal estradiol (E₂) patches in a large outpatient setting. Methods: In a retrospective study, serum E₂ levels from 18 clinics were analyzed at the Göteborg Pediatric Growth Research Center laboratory, as part of the initiation of ERT in girls with hypogonadism. Exclusion criteria were pubertas tarda and pubertal arrest. Eighty-eight observations (50 with Turner syndrome, TS) were included. Serum E₂ levels were determined by extraction + radioimmunoassay (detection limit 4 pmol/l) and analyzed in relation to the dose of Evorel® (25 µg/24 h, containing 1.60 mg estradiol hemihydrate; Janssen-Cilag Pharmaceutica N.V., Beerse, Belgium). Results: There was a linear relationship between serum E₂ and the weight-based dose, with r = 0.56, p < 0.0001 for all observations and r = 0.59, p < 0.0001 for the TS study group. Linear regression analysis for doses of 0.05-0.07 µg/kg resulted in serum levels of 17-23 pmol/l (TS 17-24 pmol/l) and doses of 0.08-0.12 µg/kg in 26-39 pmol/l (TS 27-39 pmol/l). Conclusions: For the initiation of ERT with nocturnally administered E₂ patches, we recommend reduced starting doses of 0.05-0.07 µg/kg, with the goal of mimicking E₂ levels during gonadarche. In older girls, when breast development is of high priority, the starting dose can still be 0.08-0.12 µg/kg.

Migraine in Women

This article discusses hormonal milestones and the influence that hormonal fluctuations make in the frequency and severity of migraine in women and includes information on acute, short-term, and preventive strategies for hormonally influenced migraine and the situations in which hormonal therapies may be offered. Genomic patterns in adolescent girls differentiate between menstrually related migraine and non-menstrually related migraine. The age at initiation of estrogen replacement therapy appears to be significant with respect to stroke. No increase in stroke occurred in women on low-dose (50 µg or less) transdermal estrogen replacement compared to women not using estrogen replacement. Childhood maltreatment is more common in women with migraine and depression than in women with migraine alone. Management of hormonally influenced migraine involves a clear identification of the relationship between migraine and hormone change. A thorough history and detailed diary are critical in identifying this relationship and in predicting response or following response to hormonal therapies. The evolution of migraine in an individual may be strongly driven by hormonal shifts. Although limited, clinical evidence suggests that oral contraceptive use in young women with episodic migraine may transform their pattern into chronic migraine. Thus, particular attention to changes in migraine patterns following either endogenous or exogenous hormonal changes is crucial. Providing reassurance and education that migraine is a biological disorder and providing an understanding of the role of estrogen in the frequency and severity of migraine can guide treatment choices. Pharmacologic treatments include acute therapy, with short-term and standard prevention offered where appropriate. Hormonal therapies are not first-line therapies but may be important choices for a woman with migraine whose estrogen fluctuation is continually exacerbating migraine attacks. Given the many hormonal stages during the life of a woman with migraine, therapies may vary according to hormonal stage and status. Overall wellness should also be emphasized; regular exercise, balanced diet, smoking cessation, weight control, and sleep hygiene are important in the management of migraine.

Abstract 203: Chronic and Acute Estrogen Replacement Therapy Has Different Effects in Aged Animals After Experimental Stroke

Introduction: The effect of estrogen replacement therapy (ERT) on stroke incidence and severity has been extensively debated. Clinical trials of ERT demonstrated an increased risk of stroke in treated women, but study participants were well past menopause when therapy was initiated. It has been suggested that detrimental effects of ERT may be unmasked after prolonged periods of hypoestrogenicity. To date, very few studies have examined the effect of ERT in aged animals although the timing of replacement may be critical to the neuroprotective effects of ERT. Hypothesis: We hypothesized that chronic estrogen replacement (CER) initiated in late middle age, would decrease infarct size after an induced stroke whereas acute estrogen replacement (AER) would have no beneficial effects in the aged female brain. Methods: CER was administered to aged C57BL6 mice from 17 to 20 months of age, and AER was initiated at 20 months of age. Both CER and AER treated mice were subjected to 90-minute middle cerebral artery occlusion (MCAO) at 20.5 months of age. Stroke outcomes at 24 hours of MCAO were measured. Protein levels of nuclear factor κB (NFκB), estrogen receptor α (ERα) and serum levels of pro-inflammatory cytokines were also examined. Results: Female mice that received CER showed improved stroke outcomes after MCAO (total infarct: CER vs. vehicle 34.7±2.4% vs. 58.2±2.6%; n=9/gp, p &lt;0.05); whereas females that had AER did not. CER females exhibited diminished levels of NFκB translocation compared to AER females after stroke. AER females demonstrated both an increase in nuclear NFκB and enhanced expression of pro-inflammatory cytokines. The differential NFκB translocation was related to corresponding changes in ERα expression. Aged males benefited from ERT regardless of the timing of initiation of ERT, and had significantly reduced expression of pro-inflammatory markers after stroke compared to age-matched females. Conclusions: AER worsened stroke outcomes whereas CER was protective in aged females. A pro-inflammatory milieu emerges with age in females which was attenuated by CER treatment. Interestingly both AER and CER reduced stroke injury in aged males, suggesting sexually dimorphic effects on inflammation.

Estrogen Replacement, Muscle Composition, and Physical Function: The Health ABC Study

Although the beneficial effects of estrogen use on cardiovascular and cognitive function in postmenopausal women have been recently discredited, controversy remains regarding its usefulness for maintaining skeletal muscle mass or strength. Therefore, the purpose of this study was to determine whether estrogen use is associated with enhanced muscle composition and, if so, whether this translates into improved strength and physical function. Cross-sectional analysis of 840 well-functioning community-dwelling white women (current estrogen replacement therapy (ERT) users = 259, nonusers = 581) aged 70-79 yr participating in the Health, Aging and Body Composition Study. Muscle composition of the midthigh by computed tomography included cross-sectional area (CSA) of the quadriceps, hamstrings, intermuscular fat and subcutaneous fat, and muscle attenuation in Hounsfield units (HU) as a measure of muscle density. Isometric hand grip and isokinetic knee extensor strength were assessed by dynamometry. Physical function was assessed using a summary scale that included usual 6-m walk and narrow walk speed, repeated chair stands, and standing balance. In analyses of covariance adjusted for relevant confounders, quadriceps muscle CSA and HU were greater in current ERT than non-ERT women (P < 0.05). Grip strength was also greater (P < 0.05) in women taking ERT while knee extensor strength approached significance (P < 0.10). However, differences in muscle composition and strength were modest at < or =3.3%. There was no difference by ERT status for the hamstring muscles, fat CSA, or for physical function. The associations between ERT and muscle composition and strength were minor and did not translate into improved physical function. Initiation of ERT for preservation of muscle composition and function may not be indicated.

Should progestins be blamed for the failure of hormone replacement therapy to reduce cardiovascular events in randomized controlled trials?

Many observational studies and experimental and animal studies have demonstrated that estrogen replacement therapy (ERT) or hormone replacement therapy (HRT) (estrogen plus progestin) significantly reduces the risk of coronary heart disease. Nonetheless, recent randomized controlled trials demonstrated some trends toward an increased risk of cardiovascular events rather than a reduction of risk. Recently, both the HRT and ERT arms of the Women's Health Initiative (WHI) study were terminated early because of an increased/no incidence of invasive breast cancer, increased incidence of stroke, and increased trend/no protective effects of cardiovascular disease. We discuss the controversial effects of HRT and ERT on cardiovascular system and provide a hypothesis that the failure of HRT and ERT in reducing the risk of cardiovascular events in postmenopausal women might be because of the stage of their atherosclerosis at the time of initiation of HRT or ERT.

Significance of serum CrossLaps as a predictor of changes in bone mineral density during estrogen replacement therapy; comparison with serum carboxyterminal telopeptide of type I collagen and urinary deoxypyridinoline.

The newly developed Elecsys Beta-CrossLaps/serum assay measures C-terminal telopeptide of type I collagen and has thus been proposed as a reliable serum marker for bone resorption. We investigated its usefulness for monitoring the therapeutic effect of estrogen replacement therapy on bone turnover and bone mineral density (BMD) in patients with postmenopausal osteoporosis. Serum Beta-CTx decreased by 43.2% +/- 9.2% (mean +/- SD), and 55.1% +/- 7.0% at 3 and 6 months, respectively, after initiation of estrogen replacement therapy (ERT), which was significantly greater than the respective value of urinary excretion of deoxypyridinoline (DPD) (27.8% +/- 4.1%, 34.1% +/- 4.9%, respectively) or pyridinoline cross-linked carboxyterminal telopeptide of type I collagen (ICTP) assay (14.5% +/- 4.1%, 13.1% +/- 5.0%, respectively). The percent reduction in serum Beta-CTx at 1, 3, and 6 months after initiation of ERT was significantly correlated in a negative manner with the percent increase in spinal BMD at 6 months. Further, ROC analysis to determine the significance of the percent change in bone resorption markers after 3 months of ERT in predicting the gain in spine BMD after 6 months suggested that serum Beta-CTx and urinary DPD might provide a more discriminating indicator than serum ICTP. In conclusion, the findings suggest that the Elecsys Beta-CrossLaps/serum assay provides a sensitive, and thus useful, tool for assessing bone resorption state in Japanese patients.

Estrogen replacement therapy in breast cancer survivors: a matched-controlled series.

We prospectively administered estrogen replacement therapy (ERT) to control estrogen deficiency symptoms in breast cancer survivors as part of our clinical practice. We report the consequences of ERT compared with a historical matched-control group. Two hundred seventy-seven disease-free survivors received ERT. Controls were matched for exact stage, a recurrence-free period similar to the period to ERT initiation in the ERT group, approximate age, and duration of follow-up. The mean time from breast cancer diagnosis to initiation of ERT was 3.61 (+/- 0.25) years, with a median of 1.88 years. The mean duration of ERT was 3.7 (+/- 3.01) years, with a median of 3.05 years. Hot flashes were relieved in 206 of 223 women (92%), dyspareunia/vaginal dryness in 149 of 167 women (89%), and reactive depression/anxiety/mood change in 111 of 126 women (88%). Univariate analysis demonstrated no statistical differences between the groups for age, stage, pathology at diagnosis, progesterone receptor status, local therapy, breast at risk, prior chemotherapy, and duration of follow-up. The ERT group was more likely to be estrogen receptor negative (P = 0.01), to have received prior ERT (P < 0.001), and to have received no adjuvant tamoxifen (P < 0.001). There was no significant difference between the ERT and control groups in ipsilateral primary/recurrence (5/155 v 5/143; P = 0.85), contralateral breast cancers (10/258 v 9/260; P = 0.99), or systemic metastasis (8/277 v 15/277; P = 0.13). Noncause-specific deaths in the control group numbered 15 (of 277), and in the ERT group, 7 (of 277) (P = 0.03). Overall survival favored the ERT group (P = 0.02). In these selected patients, ERT relieved estrogen deficiency symptoms and did not increase the rate or time to an ipsilateral recurrence/new primary, contralateral new primary, local-regional recurrence, or systemic metastases.

Double blind, randomized study of estradiol replacement therapy on markers of inflammation, coagulation and fibrinolysis

Estrogen replacement therapy (ERT) has been found to be associated with increased cardiovascular risk in the first year after initiation of ERT. We compared the effects of oral and transdermal estradiol (E2) replacement therapy on markers of inflammation, coagulation and fibrinolysis in a randomized double-blind trial. Forty-three healthy women were randomized 6 weeks after surgically induced menopause to receive treatment with either oral or transdermal E2 over a period of 28 weeks. At baseline and after 28 weeks, levels of serum lipids and lipoproteins, and markers of coagulation, fibrinolysis and inflammation were determined. Among fibrinolytic parameters, oral E2 shortened euglobulin clot lysis time ( P<0.05) and reduced tissue type plasminogen activator antigen ( P=0.01) and plasminogen activator inhibitor activity ( P<0.05). Among coagulation parameters, both routes of E2 replacement decreased fibrinogen levels ( P=0.002 for oral and P=0.007 for transdermal E2). Oral E2 resulted in an increase in C-reactive protein (CRP) from 2.15 (0.71–4.05) to 3.41 (1.12–5.92) mg/l ( P=0.04), while transdermal E2 showed no effect. Levels of serum amyloid A (SAA), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) did not change significantly after oral and transdermal E2. Oral E2 significantly improved the lipid profile, while transdermal E2 had a less pronounced effect. Both oral and transdermal E2 significantly reduced fasting glucose. Oral E2 was associated with a pro-inflammatory response, but at the same time improved fibrinolytic capacity, showed no pro-coagulatory effects, and acted beneficially on lipids and lipoproteins. There was no influence of transdermal E2 on markers of coagulation activation, fibrinolysis and inflammation, but it decreased fibrinogen levels significantly. Further studies are needed to explore the clinical relevance of these observations.

Estrogen replacement therapy after breast cancer: a 12-year follow-up.

In the United States, estrogen replacement therapy (ERT) is discouraged in breast cancer survivors because of concerns that hormones may reactivate the disease. Because ERT can improve quality of life and decrease morbidity from osteoporosis and cardiovascular disease, however, this policy is increasingly being challenged. From February to August 1995, 607 breast cancer survivors were interviewed concerning ERT usage. Sixty-four patients indicated they received some form of ERT after their breast cancer diagnosis. Medical records for these patients were analyzed for disease stage, surgical treatment, adjuvant treatment, estrogen and progesterone receptor status, date of initiation of ERT, type of ERT, recurrence, and final outcome. Patients receiving ERT were followed prospectively. Eight patients were excluded because they had used only vaginal cream ERT. The remaining 56 received ERT as conjugated estrogens, an estradiol patch, estropipate, or birth control pills. The median follow-up from diagnosis was 12.8 years (range, 4.7-38.9 years). The median time on ERT since diagnosis was 6.4 years (range, 1.0-20.9 years); 38% of the patients initiated ERT within 2 years of diagnosis. Estrogen receptors were positive in 28 (74%) of the 38 cases with available information. Pathological disease stage at time of diagnosis and treatment was 0 in 15 cases (27%), I in 27 (48%), and II in 14 (25%). Twenty-six patients (47%) received adjuvant chemotherapy or hormonal therapy. One local recurrence and one contralateral breast cancer occurred during the follow-up period (13.5 and 9.6 years, respectively), with no regional or distant recurrences, for a 15-year actuarial disease-free survival rate of 92.5%. There were no breast cancer deaths. Use of ERT in a cohort of breast cancer survivors with tumors of generally good prognosis was not associated with increased breast cancer events compared with non-ERT users, even over a long follow-up period.

Clinical Evaluation of the Elecsys β-CrossLaps Serum Assay, a New Assay for Degradation Products of Type I Collagen C-Telopeptides

The Elecsys beta-CrossLaps serum assay measures type I collagen degradation fragments (beta-CTx) that contain the beta-isomerized octapeptide EKAHD-beta-GGR. We investigated the analytical performance of the assay and changes in beta-CrossLaps in patients with metabolic bone diseases. The electrochemiluminescent sandwich immunoassay uses two monoclonal antibodies directed against different regions of the linear EKAHD-beta-GGR. beta-CrossLaps (beta-CTx) immunoreactivity was stable in serum and plasma stored at 4 degrees C for 24 h or at room temperature for 4 h, and it did not decrease appreciably in samples stored at -30 degrees C for 12 weeks. Nine cycles of repeated freezing-thawing did not affect serum beta-CTx. The intra- and interassay imprecision (CVs) for four samples was < or = 2.6% (n = 10) and < or = 4.1% (n = 10), respectively. The mean day-to-day biological variation (CV) was 20% in 10 postmenopausal women (n = 10 days). Serum beta-CTx and osteocalcin were correlated in patients with hyperparathyroidism (r = 0.796; P <0.0001; n = 28), chronic renal failure on hemodialysis (r = 0.784; P = 0.0003; n = 16), hypoparathyroidism (r = 0.950; P = 0.0001; n = 11), and pseudohypoparathyroidism (r = 0.987; P = 0.130; n = 4). Serum beta-CTx decreased by 47.4% +/- 8.8% (mean +/- SD) and 60.7% +/- 6.5% at 3 and 6 months, respectively, after initiation of estrogen replacement therapy in 34 women. These decreases were greater than the decreases in urinary excretion of deoxypyridinoline (31.8% +/- 3.9% and 38.1% +/- 4.4%, respectively) or pyridinoline cross-linked C-terminal telopeptide of type I collagen (15.9% +/- 3.9% and 16.9% +/- 4.6%, respectively). The Elecsys beta-CrossLaps serum assay provides a potentially useful tool for assessing bone resorption state, including its response to estrogen replacement therapy.

The effect of oophorectomy and estrogen replacement therapy on Doppler derived parameters of aortic flow

Objectives: The immediate consequences of surgical castration and estrogen replacement therapy (ERT) on left ventricular systolic performance as assessed by Doppler-derived parameters of aortic flow were examined. Methods: A follow up study comprising two groups: eight premenopausal women who underwent hysterectomy and bilateral oophorectomy and started ERT 1 week after surgery – the study group, and a control group consisted of eight premenopausal women who did not start ERT following hysterectomy. Doppler echocardiography was performed before surgery, 1 week and 1 month post surgery. Results: In both groups significant increase in heart rate was observed after 1 week, remaining high after 1 month in the control group only. The early post-operative period in all women was characterized by an increase in aortic flow velocity, but was statistically significant in the study group only. After initiation of ERT a significant decrease in peak flow velocity (PFV) and mean acceleration (MA) was recorded. Conclusions: Changes in estradiol level may be associated with alterations in left ventricular function. The initial and acute effect of estrogen on the heart muscle after surgical castration is towards a decrease in Doppler-derived parameters of aortic flow. Whether these effects represent a depression of left ventricular function, or alternatively, reflect peripheral vasculature reactivity, requires further evaluation.

Estrogen Replacement Therapy After Localized Breast Cancer: Clinical Outcome of 319 Women Followed Prospectively

To determine whether estrogen replacement therapy (ERT) alters the development of new or recurrent breast cancer in women previously treated for localized breast cancer. Potential participants (n = 319) in a trial of ERT after breast cancer were observed prospectively for at least 2 years whether they enrolled onto the randomized trial or not. Of 319 women, 39 were given estrogen and 280 were not given hormones. Tumor size, number of lymph nodes, estrogen receptors, menopausal status at diagnosis, and disease-free interval at the initiation of the observation period were comparable for the trial participants (n = 62) versus nonparticipants (n = 257) and for women on ERT (n = 39) versus controls (n = 280). Cancer events were ascertained for both groups. Patient and disease characteristics were comparable for the trial participants versus nonparticipants, as well as for the women on ERT versus the controls. One patient in the ERT group developed a new lobular estrogen receptor-positive breast cancer 72 months after the diagnosis of a ductal estrogen receptor-negative breast cancer and 27 months after initiation of ERT. In the control group, there were 20 cancer events: 14 patients developed new or recurrent breast cancer at a median time of 139.5 months after diagnosis and six patients developed other cancers at a median time of 122 months. ERT does not seem to increase breast cancer events in this subset of patients previously treated for localized breast cancer. Results of randomized trials are needed before any changes in current standards of care can be proposed.

Timing of Estrogen Replacement Therapy Following Hysterectomy With Oophorectomy for Endometriosis

Objective: To determine whether the immediate initiation of estrogen replacement therapy (ERT) in the postoperative period increases the incidence of symptom recurrence following total abdominal hysterectomy (TAH) with bilateral salpingo-oophorectomy (BSO) for the treatment of endometriosis. Methods: In a retrospective cohort study, 95 women who underwent TAH with BSO for endometriosis at the Johns Hopkins Hospital during 1979–1991 and who subsequently received ERT were identified by computer search. Follow-up information was obtained from medical records, outpatient charts, and telephone surveys. Pain recurrence in patients who started ERT within 6 weeks after surgery and in those who delayed ERT for more than 6 weeks was compared and adjusted for length of patient follow-up and other covariates. Results: Sixty women began ERT within the immediate postoperative period, and four (7%) of them had recurrent pain; 35 women began ERT more than 6 weeks after surgery, and seven (20%) of them had recurrent pain. The mean length of follow-up was 57 months. The difference in the crude rate of symptom recurrence following early and delayed initiation of ERT after TAH with BSO was not statistically significant ( P = .09). Controlling for length of patient follow-up, no significant differences were observed between the two groups. Adjusting for covariates of stage, age, and postoperative adjunct medroxyprogesterone therapy, those who started ERT more than 6 weeks after surgery had a relative risk of 5.7 (95% confidence interval 1.3, 25.2) for pain recurrence. Conclusion: Although the number of patients in the study was too small to reach statistical significance in all analyses, these findings suggest that patients who begin ERT immediately after TAH with BSO are at no greater risk of recurrent pain than those who delay ERT for more than 6 weeks.

Estrogen Replacement Therapy in Women With Prior Diagnosis and Treatment for Breast Cancer

We followed 49 women who underwent a minimum of 2 years estrogen replacement therapy (ERT) after diagnosis and treatment for localized breast cancer. Forty-three women were treated with oral ERT. In this group, the median age at the time of cancer diagnosis was 46 years (range 26 to 66 years), and ERT was begun a median of 84 months after diagnosis (range 0 to 286 months). The patients were followed for a median of 144 months after cancer diagnosis (range 46 to 324 months), and the median duration of ERT was 31 months (range 24 to 142 months). For six women, ERT was administered as a vaginal cream application. In this group, the median age at time of cancer diagnosis was 46 years (range 38 to 57 years), and ERT was begun a median of 49 months after diagnosis (range 24 to 61 months). The patients were followed for a median of 95 months after cancer diagnosis (range 72 to 154 months), and the median duration of ERT was 47 months (range 27 to 80 months). One patient experienced disease recurrence; she had received surgery for a stage I, estrogen receptor (ER)-positive lesion. The patient began ERT 30 months after cancer diagnosis and developed a recurrent ER-negative tumor 56 months after initiation of ERT. She remained alive without evidence of disease for 10 years since initial diagnosis of breast cancer. Despite the inherent limitations of retrospective experiential data and the need for prospective, randomized trials to assess the safety of ERT, the present observations suggest that ERT does not appear to have a pronounced adverse effect on cancer outcome. Nevertheless, until appropriate clinical trials determine that ERT is safe, caution is needed.

Estrogen Replacement Therapy in Women with Prior Diagnosis and Treatment for Breast Cancer

We followed 49 women who underwent a minimum of 2 years estrogen replacement therapy (ERT) after diagnosis and treatment for localized breast cancer. Forty-three women were treated with oral ERT. In this group, the median age at the time of cancer diagnosis was 46 years (range 26 to 66 years), and ERT was begun a median of 84 months after diagnosis (range 0 to 286 months). The patients were followed for a median of 144 months after cancer diagnosis (range 46 to 324 months), and the median duration of ERT was 31 months (range 24 to 142 months). For six women, ERT was administered as a vaginal cream application. In this group, the median age at time of cancer diagnosis was 46 years (range 38 to 57 years), and ERT was begun a median of 49 months after diagnosis (range 24 to 61 months). The patients were followed for a median of 95 months after cancer diagnosis (range 72 to 154 months), and the median duration of ERT was 47 months (range 27 to 80 months). One patient experienced disease recurrence; she had received surgery for a stage I, estrogen receptor (ER)-positive lesion. The patient began ERT 30 months after cancer diagnosis and developed a recurrent ER-negative tumor 56 months after initiation of ERT. She remained alive without evidence of disease for 10 years since initial diagnosis of breast cancer. Despite the inherent limitations of retrospective experiential data and the need for prospective, randomized trials to assess the safety of ERT, the present observations suggest that ERT does not appear to have a pronounced adverse effect on cancer outcome. Nevertheless, until appropriate clinical trials determine that ERT is safe, caution is needed.