Pathologic and clinical tumor size discordance in early-stage cervical cancer: Does it matter?

OBJECTIVE: The objective of this study was to assess the rate of discordance between clinical and pathologic tumor size for women with stage IB1 cervical cancer (FIGO 2009 criteria), assess risk factors for discordance, and determine the impact of discordance on oncologic outcomes. METHODS: This was a secondary analysis of a prior multi-institutional retrospective review of patients diagnosed with stage IB1 (FIGO 2009 staging) cervical cancer undergoing radical hysterectomy between 2010 and 2017. Demographic, clinicopathologic, and oncologic data were collected. Pathologic upstaging was defined as having a preoperative diagnosis of stage IB1 cervical cancer with pathology demonstrating a tumor size >4 cm. Demographic and clinicopathologic data was compared using chi-square, fisher exact or 2-sided t-test. Survival was estimated using the Kaplan-Meier method. RESULTS: Of the 630 patients, 77 (12%) were upstaged. Patients who were upstaged had lower rates of preoperative conization (p < .001) or preoperative tumor sizes ≤2 cm (p < .001). Upstaged patients had increased odds of deep stromal invasion, lymphovascular space invasion, positive margins and positive lymph nodes. Almost 88% of upstaged patients received adjuvant therapy compared to 29% of patients with tumors ≤4 cm (odds 18.49, 95% CI 8.99-37.94). Finally, pathologic upstaging was associated with an increased hazard of recurrence (hazard ratio [HR] 1.95, 95% CI 1.03-3.67) and all-cause death (HR 2.31, 95% CI 1.04-5.11). CONCLUSIONS: Pathologic upstaging in stage IB1 cervical cancer is relatively common. Upstaging is associated with an 18-fold increased risk of receipt of adjuvant therapy. Patients undergoing preoperative conization and those with tumors <2 cm had lower risks of upstaging. Improvement in preoperative assessment of tumor size may better inform primary treatment decisions.

Randomized controlled trials define shape of dose response for Pollinex Quattro Birch allergoid immunotherapy.

BACKGROUND: The Birch Allergoid, Tyrosine Adsorbate, Monophosphoryl Lipid A (POLLINEX® Quattro Plus 1.0 ml Birch 100%) is an effective, well-tolerated short course subcutaneous immunotherapy. We performed 2 phase II studies to determine its optimal cumulative dose. METHODS: The studies were conducted in Germany, Austria and Poland (EudraCT numbers: 2012-004336-28 PQBirch203 and 2015-000984-15 PQBirch204) using a wide range of cumulative doses. In both studies, subjects were administered 6 therapy injections weekly outside the pollen season. Conjunctival Provocation Tests were performed at screening, baseline and 3-4 weeks after completing treatment, to quantify the reduction in Total Symptom Scores (as the primary endpoint) with each cumulative dose. Multiple Comparison Procedure and Modeling analysis was used to test for the dose response, shape of the curve and estimation of the median effective dose (ED50 ), a measure of potency. RESULTS: Statistically significant dose responses (P < .01 & .001) were seen, respectively. The highest cumulative dose in PQBirch204 (27 300 standardized units [SU]) approached a plateau. Potency of the PQBirch was demonstrated by an ED50 2723 SU, just over half the current dose. Prevalence of treatment-emergent adverse events was similar for active doses, most being short-lived and mild. Compliance was over 85% in all groups. CONCLUSION: Increasing the cumulative dose of PQBirch 5.5-fold from 5100 to 27 300 SU achieved an absolute point difference from placebo of 1.91, a relative difference 32.3% and an increase in efficacy of 50%, without compromising safety. The cumulative dose response was confirmed to be curvilinear in shape.

Work-related health advice in primary care.

BACKGROUND: The dangers of long-term sickness absence and worklessness are well recognized. In the UK, the occupational health (OH) community was challenged to seek new partners to support health in working age people. A National Health Service OH service and Leicestershire general practice set up a pilot clinic to provide work-related health advice in primary care. AIMS: To recruit 100 patients to an OH clinic in general practice and record their demographic characteristics, diagnoses and occupational outcomes. METHODS: Pre-booked 30 min appointments for work-related health consultations in general practice were offered over 12 months. Consultations were recorded electronically and questionnaire feedback invited 3-6 months later. The main outcome was subjective reporting of benefit and workplace adjustments. RESULTS: Ninety-six patients attended OH appointments in general practice, 86 were in employment: 49 on sick leave at the time of their consultation and 10 were workless. Mental health and musculoskeletal problems accounted for the most common diagnoses. Following their consultation, 29% of patients reported workplace adjustments which were beneficial to them. None of the workless reported a return to employment. CONCLUSIONS: Patients will access work-related health advice in primary care. Extended OH consultations by general practitioners can achieve positive self-reported outcomes for patients in employment.

Preoperative 6-minute walk test adds prognostic information to Euroscore in patients undergoing aortic valve replacement.

AIMS: The authors investigated the additive prognostic value of the 6-minute walk test (6MWT) to Euroscore in patients with severe aortic stenosis undergoing aortic valve replacement (AVR) METHODS AND RESULTS: 208 patients with severe AS underwent the 6MWT before AVR, as part of a randomised trial (ASSERT) comparing stented and stentless aortic valves. Clinical follow-up was available for 200 patients up to 12 months. The rate of death, myocardial infarction (MI) or stroke (time to first event) was 13% (n = 14) in patients walking <300 metres compared to 4% (n = 4) in those who walked > or =300 metres (p = 0.017). When rate of death, MI or stroke by Euroscore risk was stratified by 6-minute walking distance, the 6MWT added prognostic information. In a Cox regression analysis 6MWT distance was the only variable retained as an independent predictor of the composite outcome of death, MI or stroke at 12 months (HR 0.28 95% CI 0.09 to 0.85, p = 0.025). CONCLUSIONS: The 6MWT is safe and feasible to carry out in patients with severe aortic stenosis before AVR, and provides potentially important functional and prognostic information to clinical assessment and the Euroscore risk score.

Pulmonary metastasectomy in colorectal cancer: time for a trial.

Pulmonary metastasectomy is undertaken for a range of cancers. The questions we raise here are specifically related to colorectal cancer, the commonest tumour for which pulmonary metastasectomy is undertaken. The primary objective of metastasectomy is to increase survival. There are no randomised trials in support of this practice nor are there any other forms of controlled studies. We present a critical look at the assumption of efficacy for this surgery and propose that a trial is needed and suggest a trial design.

Use of a (proposed) standard protocol to validate Terumo TSCD-II connections between dissimilar blood bag tubing.

BACKGROUND AND OBJECTIVES: ISO standards for blood bags do not adequately define and control the dimensions of blood bag transfer tubing. This lack of standardization presents potential difficulties when making sterile connections between the wide range of tubing that has evolved in the absence of such standards. We aim to validate the suitability of the TSCD-II and provide a minimum standard for assessing the suitability of sterile connections (welds) between dissimilar tubing. MATERIALS AND METHODS: The Terumo TSCD-II was used in this study to connect by hermetic welding seven tubing types with a wide range of dimensions from five suppliers. Thirty sterile connections were made between each combination split between dry/dry, wet/wet and dry/wet connections. Welds were assessed for visual defects, by tensile stress test (TST) and pressure tests. RESULTS: All welds passed visual inspection and pressure tests. All welds had a minimum tensile strength of greater than 40 N and mean of greater than 45 N. CONCLUSION: Successful connections have been made between dissimilar tube types and this work does not support the requirement for 'tight' tubing dimensional specifications. We have recommended to the ISO Technical Committee 76 Work Group 1 that ISO 3826-1 be revised and should include a minimum standard validation protocol for joining dissimilar tubing.

Comparison of hypertonic saline and alternate-day or daily recombinant human deoxyribonuclease in children with cystic fibrosis: a randomised trial.

BACKGROUND: Daily recombinant human deoxyribonuclease (rhDNase) is an established but expensive treatment in cystic fibrosis. Alternate-day treatment, if equally effective, would reduce the drug cost. Hypertonic saline improved lung function to the same degree as rhDNase in short-term studies. We compared the effectiveness of daily rhDNase, hypertonic saline, and alternate-day rhDNase in children with cystic fibrosis. METHODS: In an open cross-over trial, 48 children were allocated in random order to 12 weeks of once-daily rhDNase (2.5 mg), alternate-day rhDNase (2.5 mg), and twice-daily 5 mL 7% hypertonic saline. The primary outcome was forced expiratory volume in 1 s (FEV(1)). Secondary outcomes were forced vital capacity, number of pulmonary exacerbations, weight gain, quality of life, exercise tolerance, and the total costs of hospital and community care. FINDINGS: Mean FEV(1) increased by 16% (SD 25%), 14% (22%), and 3% (21%) with daily rhDNase, alternate-day rhDNase, and hypertonic saline, respectively. There was no difference between daily and alternate-day rhDNase (2% [95% CI -4 to 9], p=0.55). However, daily rhDNase showed a significantly greater increase in FEV(1) than hypertonic saline (8% [2 to 14], p=0.01). The average difference in 12-week cost between daily and alternate-day rhDNase was pound513 (95% CI -546 to 1510) and that between daily rhDNase and hypertonic saline was pound1409 (440 to 2318). None of the secondary clinical outcomes showed significant differences between treatments. INTERPRETATION: Hypertonic saline, delivered by jet nebuliser, is not as effective as daily rhDNase, although there is variation in individual response. There is no evidence of a difference between daily and alternate-day rhDNase.

The prevention of osteoporosis using sequential low-dose hormone replacement therapy with estradiol-17 beta and dydrogesterone.

Low-dose hormone replacement therapy (HRT) in postmenopausal women may produce fewer side-effects but its efficacy in the prevention of bone loss and osteoporosis is not established. To address this we compared the effect of 1 mg estradiol-17 beta with a 2 mg dose, in combination with cyclical dydrogesterone, in the prevention of postmenopausal bone loss. We conducted a multicenter double-masked prospective randomized, placebo-controlled study in 595 apparently healthy postmenopausal women randomized to either placebo, or continuous oral estradiol-17 beta 1 mg or 2 mg with sequential dydrogesterone for 2 years. The primary endpoint was the percentage change from baseline in bone mineral density (BMD) in the lumbar spine (LS) and femoral neck (FN) of actively treated groups compared with placebo. Women taking either 1 mg or 2 mg estradiol-17 beta showed a significant increase in BMD of the LS (mean +/- SD, 5.2 +/- 3.8% and 6.7 +/- 4.0% respectively, both p < 0.001) whilst BMD in the placebo group decreased (-1.9 +/- 4.0%). Increases were also observed in FN BMD in both treated groups (2.7 +/- 4.2% and 2.5 +/- 5.2% respectively, both p < 0.001) in contrast to the placebo group (-1.8 +/- 4.8%). The oldest women showed the greatest treatment response. One milligram estradiol-17 beta in combination with dydrogesterone is effective in conserving LS and proximal femur bone mass, both of which are clinically important sites of osteoporotic fracture, and is as effective as 2 mg in preventing FN bone. The lower dose of estradiol-17 beta is a particularly suitable treatment for osteoporosis management in older women since it should minimize side-effects and improve the acceptability of HRT.

17beta-estradiol (1 mg/day) continuously combined with dydrogesterone (5, 10 or 20 mg/day) increases bone mineral density in postmenopausal women.

Although the minimal dose of 17beta-estradiol in hormone replacement regimens was originally considered to be 2 mg/day, it is now increasingly accepted that a lower dose of 1 mg/day is effective in protecting women from the detrimental effects of the menopause. A 1-year, multicentre, double-blind, randomised study was conducted in 214 healthy postmenopausal women in order to assess the effect of 17beta-estradiol (1 mg/day) continuously combined with dydrogesterone (5, 10 or 20 mg/day) in preventing bone loss. Bone mineral density (BMD) was evaluable in 177 women who completed the study. In all women, a statistically significant increase from baseline in lumbar vertebrae (L2-L4) BMD was seen after 6 months ( + 2.4%; p < 0.01); this increase was somewhat greater after 12 months ( + 3.6%; p < 0.01). Similar effects were seen in the hip. After 6 months, BMD in the femoral neck, Ward's triangle and trochanter had increased by 0.20% (not significant [n.s.]), 0.32% (n.s.) and 1.08% (p < 0.01), respectively, compared with baseline. Greater increases were again seen after 12 months ( + 1.16%, + 1.62% and + 2.83%, respectively), all of which were statistically significant (p < 0.01) compared with baseline. The change in BMD from baseline did not differ significantly between the three dydrogesterone dosages for either L2-L4 or hip. All dosages were well-tolerated and amenorrhoea was achieved in over 70%. In conclusion, 17beta-estradiol (1 mg/day) continuously combined with dydrogesterone (5, 10 or 20 mg/day) results in a significant increase in lumbar vertebrae and hip BMD in postmenopausal women. The lower dose of oestrogen and the avoidance of cyclical bleeding make this a particularly suitable regimen for the prevention and treatment of osteoporosis in older women.

Standardisation of glutaraldehyde-modified tyrosine-adsorbed tree pollen vaccines containing the Th1-inducing adjuvant, monophosphoryl lipid A (MPL).

BACKGROUND: a new range of allergy vaccines has been developed by the introduction of a relatively new Th1-inducing adjuvant known as 3-deacylated monophosphoryl lipid A (MPL). MPL adjuvant is of natural origin, derived from the lipopolysaccharide of Salmonella minnesota R595. This adjuvant is incorporated in a glutaraldehyde-modified pollen extract adsorbed to L-tyrosine (Pollinex Quattro). A major potential benefit provided by MPL adjuvant is the promotion of a Th1 response which enhances the efficacy of allergy vaccination and can consequently allow a reduction in the number of injections required for treatment. The standardisation of Pollinex Quattro tree pollen allergy vaccine is described and we include details of some innovative analytical procedures. METHODS AND RESULTS: an essential feature of the analytical strategy is the assay of the MPL adjuvant using a recently developed HPLC technique. The adjuvant has a complex chemical structure and the analysis is illustrated in detail. We give a full picture of the vaccine standardisation by describing biochemical and immunological characterisation of the allergen extract, together with some brief manufacturing details. CONCLUSIONS: a high overall level of standardisation is illustrated by a number of different tests applied to all stages of vaccine manufacture. Tree pollen allergen potency is measured following the pollen extraction, chemical modification and formulation as a tyrosine adsorbate. Good batch-to-batch reproducibility is shown. The HPLC assay for MPL adjuvant showed high quality resolution which did not vary when measuring raw material or when incorporated in the vaccine and the technically complex assay is shown to be reliable.

DXA longitudinal quality control: a comparison of inbuilt quality assurance, visual inspection, multi-rule Shewhart charts and Cusum analysis.

The performance of dual-energy X-ray absorptiometry (DXA) instruments can be monitored using various quality control (QC) procedures. It has not been established which of these is most appropriate. The aim of this study was to determine which of four QC procedures is the best to use for longitudinal monitoring. Eighteen centres with DXA instruments scanned an aluminium spine phantom weekly for up to 16 months, and the bone mineral density data were used for the QC procedures. The methods investigated were the instrument's inbuilt quality assurance (QA) procedure, visual inspection, multi-rule Shewhart control charts, and Cusum analysis using a truncated-V mask. True and false positive fractions (TPF and FPF) of each method were calculated, including those for a range of action levels for the Shewhart charts and dimensions of the Cusum mask. For Shewhart, the action levels giving the most desirable TPF and FPF were whole multiples of the standard deviation (SD). For Cusum, the most desirable mask dimensions were 3.6 SD for the total height of the vertical section and 0.9 SD per data point for the gradient of the wings. Predictive power of each method as a means of fault detection was decided by the number of faults detected out of a total of 8 non-mechanical faults subsequently diagnosed. The inbuilt QA detected 2, visual inspection 7, Shewhart chart 7 and Cusum analysis 7. The FPFs were: visual inspection 0.09, Shewhart 0.04, Cusum 0.08. At these levels of FPF, the average time in days (range) from onset of a fault to detection was 39 (6-82) for visual inspection, 39 (4-116) for Shewhart and 21 (1-49) for Cusum. All three "phantom" methods are excellent for DXA QC, with modified Cusum analysis being the most effective. The inbuilt QA appears of little use on its own for longitudinal QC.

Evaluation of the European Spine Phantom in a multi-centre clinical trial.

The European Spine Phantom (ESP) has recently been developed as a universal standard for instruments measuring bone density. The ESP is composed of three semi-anthropomorphic hydroxyapatite vertebrae of varying densities surrounded by soft tissue equivalent plastic designed to resemble human bone and soft tissue when scanned on bone densitometers. In multi-centre studies it is particularly important to verify that each participating bone densitometer is performing in a stable and linear fashion. The aim of this study was to evaluate the ESP within the context of a multi-centre clinical trial. Eighteen centres in the UK and Canada with dual-energy X-ray absorptiometry (DXA) instruments (Lunar DPX, DPX-alpha and DPX-L) participated in the study. The ESP was scanned 10 times on each instrument without repositioning using standardized protocols. The precision of the bone mineral density (BMD) measurements (LI-3) expressed as a coefficient of variation ranged from 0.4% to 1.1% (mean 0.7%). The mean BMD of each instrument was expressed as a percentage difference from the overall mean and ranged from -1.33% to 1.33%. Linear regression analysis showed that all instruments behaved in a linear fashion across the range of densities with correlation coefficients all > or = 0.999 and standard errors of the estimate < 1.5% of the mean BMD ESP value. The data from this study demonstrate that the ESP is a useful phantom for assessing the linearity, stability and differences between DXA instruments from one manufacturer.

Intranasal salmon calcitonin for the prevention and treatment of postmenopausal osteoporosis.

In a randomized, double-blind, placebo-controlled trial, we have studied the effects of intranasal salmon calcitonin (SCT) on bone mineral density (BMD) and biochemical markers of bone turnover over a period of 2 years. Our study comprised 117 Caucasian postmenopausal women, otherwise healthy apart from reduced bone density. They received either intranasal synthetic SCT (200 IU either three times weekly or daily) or placebo. Compared with placebo, daily intranasal calcitonin resulted in no significant bone loss in the lumbar spine, as assessed by dual photon absorptiometry, over the 2-year study period (P < 0.02). In this group, women more than 5 years postmenopause, with the lowest baseline bone mass, showed the greatest response to this treatment, with a total increase placebo in lumbar spine BMD of 3.1%. Significant spinal bone loss (P < 0.005) occurred in women receiving either placebo or thrice-weekly calcitonin. Although the rates of bone loss in the proximal femur were not significantly different in the three groups, there were differences over time. Whereas bone loss in the daily calcitonin group was insignificant, women who received placebo or thrice-weekly calcitonin experienced significant bone loss (P < 0. 001). No significant changes in biochemical markers were observed in any group. Therapy was well tolerated and there were no significant treatment-related adverse events. We conclude that intranasal SCT 200 IU daily is effective and safe for the prevention of bone loss in postmenopausal women with reduced bone mass.

Role of oral pamidronate in preventing bone loss in postmenopausal women.

We have performed a 2-year prospective double-masked study to determine whether the bisphosphonate pamidronate can prevent bone loss in postmenopausal women and its optimal dosage regimen. One hundred and twenty-one such women (mean +/- SD age 57.6 +/- 3.4 years; mean +/- SD time since menopause 7.5 +/- 3.5 years) were randomized to receive either oral pamidronate (300 mg/day) for 4 weeks every 4 months (group A), oral pamidronate (150 mg/day) for 4 weeks every 2 months (group B) or identical placebo capsules (group C). Bone mineral density (BMD) measurements at the lumbar spine and proximal femur were performed at baseline and at 6-month intervals for 2 years using dual-energy X-ray absorptiometry. BMD at the lumbar spine (L2-4) increased significantly in groups A and B after 2 years of treatment (mean +/- SD 2.8 +/- 2.1% and 3.0 +/- 2.9% respectively, both p < 0.001) but decreased in the placebo group (-1.6 +/- 3.1%, p < 0.01). Identical results were seen for BMD at the femoral neck, which increased significantly in groups A and B after 2 years of treatment (1.2 +/- 2.3% and 1.3 +/- 2.9% respectively, both p < 0.05) but decreased in the placebo group (-1.9 +/- 3.9%, p < 0.05). There were significant differences over 2 years between the groups at all anatomical sites (lumbar spine, femoral neck and trochanteric region, all p < 0.001; Ward's triangle, p < 0.01). However, there were no significant differences between groups A and B, suggesting that the two treatment regimens were equally effective in conserving BMD. There were, however, marked differences in tolerability between the two treatment regimens: 13 women (34%) in group A withdrew from the study because of side-effects, but only 5 women (12%) in group B, which was comparable with placebo. These data demonstrate that intermittent oral pamidronate will prevent bone loss from the lumbar spine and proximal femur of postmenopausal women, and that the more frequent but lower dose regimen is well tolerated.

Body fat distribution, rather than overall adiposity, influences serum lipids and lipoproteins in healthy men independently of age.

PURPOSE: We investigated the relationships between the amount and distribution of body fat and fasting serum lipids and lipoproteins to explore whether coronary artery disease (CAD) risk may be mediated through effects on the serum lipid profile. PATIENTS AND METHODS: We determined serum total cholesterol and triglyceride, low-density lipoprotein cholesterol, high-density lipoprotein (HDL) cholesterol, and HDL subfractions 2 and 3 in 103 healthy men, aged 21 to 77 years (mean 48.7). The amount and distribution of fat were determined directly by dual energy X-ray absorptiometry. Adiposity was determined as the ratio between total body fat tissue and total body lean tissue, while fat distribution was taken as the ratio between the mass of fat tissue in the android (central) and gynoid (hip and thigh) regions. RESULTS: Univariate analysis showed both adiposity and fat distribution to be correlated with total serum cholesterol and triglyceride concentrations (adiposity r = .20, .21; both P < 0.05: fat distribution r = .25, .38; P < 0.05, P < 0.001, respectively). Fat distribution was also negatively correlated with HDL2 cholesterol (r = -.20, P < 0.05). In multiple linear regression analysis, neither age nor adiposity was significantly correlated with any serum lipid or lipoprotein concentration, while increasing android-to-gynoid ratio was independently associated with elevated total serum triglyceride (r = .40, P < 0.01) and decreased HDL2 (r = -.25, P < 0.05) concentrations. CONCLUSIONS: The association of both age and overall adiposity with the fasting serum lipid profile are mediated via their correlations with body fat distribution. In men, the distribution, rather than the amount, of body fat is related to adverse changes in serum lipids and lipoproteins, and hence potentially to increased CAD risk.

Relationships between insulin metabolism, serum lipid profile, body fat distribution and blood pressure in healthy men.

Insulin resistance and hyperinsulinaemia may be important in a cluster of coronary heart disease-related metabolic disturbances known as the insulin resistance syndrome. Whether the relationships between insulin and other features of the syndrome are independent of the amount and distribution of body fat is uncertain. We have investigated these relationships in 103 healthy males, using dual-energy X-ray absorptiometry to measure body fat directly. Volunteers underwent an intravenous glucose tolerance test (IVGTT), from which insulin sensitivity, secretion and elimination were determined by mathematical modelling analysis. Independently of adiposity and body fat distribution, serum triglyceride concentration was correlated with fasting C-peptide concentration and second-phase intravenous glucose tolerance test insulin concentration (r = 0.42, P < 0.001; r = 0.28, P < 0.05). High density lipoprotein subfraction 2 (HDL2) cholesterol was correlated with fasting C-peptide, first-phase IVGTT insulin concentration, and the hepatic insulin throughout index (r = -0.15 -0.20, -0. 20 respectively, all P < 0.05). The association of HDL2 cholesterol with the hepatic throughput index was additionally independent of serum triglyceride concentration (r = -0.18, P < 0.05). Our results suggest that relative hyperinsulinaemia leads to elevated triglyceride concentration, independently of body fat mass and distribution. Furthermore, the independent association of HDL2 cholesterol with hepatic insulin throughput confirms that hepatic insulin processing may may directly influence lipoprotein metabolism.

Gonadotropin-releasing hormone analogue (goserelin) plus hormone replacement therapy for the treatment of endometriosis: a randomized controlled trial.

OBJECTIVE: To determine whether treatment of endometriosis with a GnRH analogue (GnRH-a; goserelin) combined with continuous estrogen and progestogen hormone replacement therapy (HRT) would prevent the hypoestrogenic effects, including loss of bone density, while maintaining efficacy for treatment of endometriosis. DESIGN: Randomized controlled trial. PATIENTS: Fifty premenopausal women with laparoscopically diagnosed endometriosis (revised American Fertility Score for endometriosis implants equal to four or greater) and significant symptoms of dysmenorrhoea, dyspareunia, and other pelvic pain. INTERVENTION: Patients were randomized to receive either goserelin alone, 3.6 mg SC depot every 4 weeks for 24 weeks, or goserelin, 3.6 mg SC depot every 4 weeks for 24 weeks, plus HRT (25 micrograms transdermal 17 beta E2 daily and 5 mg medroxyprogesterone acetate orally daily) for 20 weeks commencing with the second goserelin injection. RESULTS: There was a significant reduction in the extent of pelvic endometriosis in both groups, with no difference between the groups. Both groups experienced an improvement in symptoms and signs, again with no difference between groups. Hypoestrogenic side effects of hot flushes and loss of libido were significantly less in the group that received HRT. The amount of bone mineral density loss was significantly less in the HRT group at the lumbar spine, although it was not prevented completely. CONCLUSION: The addition of HRT to GnRH-a for the treatment of endometriosis did not reduce the efficacy of treatment, and adverse hypoestrogenic effects were decreased, although not abolished.