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Biomedical subjects

J-Y Reginster

Publications and source records attributed to J-Y Reginster.

At least 37 records · Page 2Linked to original sources
PubMed2005

[Methodology of the inquiry MISSION (menopause, breast cancer risk, morbidity and prevalence)].

OBJECTIVE: The ambition of this article is to detail and to explain the methodology of the study named MISSION (Menopause: breast cancer risk, morbidity and prevalence). The aims of MISSION are to determine the prevalence of breast cancer and global morbidity in France among menopausal women treated or not with hormone replacement therapy (HRT) and followed by a gynecologist. MATERIAL AND METHOD: 6600 menopausal women [3300 with HRT -- ie for estrogen: only estradiol via oral or transdermal administration; for progestogen: natural progesterone or assimiled or one pregnane derived (excluding medroxyprogesterone acetate) or non-pregnane derived -- and 3300 without HRT] will be enrolled in France between January 5 2004 and February 28 2005 by 825 gynecologists, members or not of the National Federation of Medical Gynecologists (FNCGM). This study design is a historico-prospective with case randomization. MISSION is conducted by a Theramex-Merck Laboratories initiative in collaboration with a WHO (World Health Organization) Collaborating Center for Public Health Aspects of Rheumatic Diseases and a multidisciplinary expert group. CONCLUSION: First results of this study will contribute to better knowledge of women health.

Breast Neoplasms↗
PubMed2005

Oral and intravenous ibandronate in the management of postmenopausal osteoporosis: a comprehensive review.

Convenient strategies are needed for postmenopausal osteoporosis management. Current oral bisphosphonates are effective and generally well tolerated, but are hampered by strict dosing requirements. Less frequent dosing schedules are expected to improve adherence to therapy and hence outcomes. Ibandronate is a potent, nitrogen-containing bisphosphonate in ongoing clinical development exploring its potential to be administered less frequently than at weekly intervals. Uniquely, ibandronate can be administered either orally or as an intravenous (i.v.) injection, with a between-dose interval of >2 months. In postmenopausal women, oral ibandronate, when administered either daily or intermittently, has demonstrated robust antifracture efficacy at the spine (62% [p=0.0001] and 50% [p=0.0006] risk reduction versus placebo), accompanied by significant increases in bone mineral density (BMD) at the spine and hip, and suppression of bone turnover markers. Studies of intermittent i.v. ibandronate injections in postmenopausal women have shown dose-related BMD gains and bone turnover marker suppression comparable to those obtained after a similar duration of treatment with the proven effective oral ibandronate regimen. Furthermore, in a trial conducted in patients with corticosteroid-induced osteoporosis, intermittent i.v. ibandronate injections reduced vertebral fracture risk by 62% versus an active control (p=0.043). In all these trials, the oral and i.v. ibandronate regimens were well tolerated. Ongoing, large multinational clinical trials are investigating two intermittent ibandronate regimens: once-monthly oral and intermittent i.v. injections. These simple ibandronate regimens are expected to provide the optimal combination of efficacy, tolerability and patient convenience, leading to improved treatment adherence and thus, enhanced outcomes in postmenopausal osteoporosis.

Administration, Oral↗
PubMed2004

A naturalistic study of the determinants of health related quality of life improvement in osteoarthritic patients treated with non-specific non-steroidal anti-inflammatory drugs.

OBJECTIVES: To capture changes in the quality of life (QoL) occurring in patients with osteoarthritis (OA) during treatment with non-specific non-steroidal anti-inflammatory drugs (NSAIDs) and to identify factors that predict such changes. METHODS: A naturalistic, prospective follow up of 783 patients with OA in whom primary care physicians decided to start treatment with non-selective NSAIDs. Short Form-36 (SF-36) and the Western Ontario and McMaster Universities OA index (WOMAC) were assessed at baseline and after 3 months. Baseline results were compared with QoL values in 4800 subjects randomly selected from the general population. Multiple regression analysis was performed to identify determinants of QoL at baseline and measures influencing changes in SF-36 or WOMAC during follow up. RESULTS: All QoL dimensions were significantly (p<0.01) decreased in patients with OA compared with controls. Significant improvement (p<0.05) in four dimensions of the SF-36 (vitality, role emotional, role physical, bodily pain) and in all components of the WOMAC was seen between baseline and month 3. Older age, female sex, longer duration of OA, and a higher number of comorbidities were the major determinants of a poor QoL at baseline. Maximal benefit from non-specific NSAIDs was seen in patients with the most severe impairment in QoL and the shortest duration of OA. CONCLUSION: OA negatively impacts all dimensions of the QoL. Non-specific NSAIDs improve the QoL in patients with OA treated in a "real life setting". The profile of patients receiving maximal benefit from such treatment may be of interest for health providers, enabling them to decide who should preferentially be given cytoprotective treatments or coxibs.

Adult↗
PubMed2004

Lumiracoxib is effective in the treatment of osteoarthritis of the knee: a 13 week, randomised, double blind study versus placebo and celecoxib.

OBJECTIVES: To compare the efficacy and safety of lumiracoxib with placebo and celecoxib for osteoarthritis OA in a 13 week, multicentre, randomised, double blind study. METHODS: After a 37 day washout period for nonsteroidal antiinflammatory drugs, 1702 patients with knee OA were randomised to lumiracoxib 200 or 400 mg once daily od, celecoxib 200 mg od, or placebo 2221. A visual analogue scale VAS pain intensity > or =40 mm was required. Primary efficacy variables were OA pain intensity VAS mm in the target knee, patients global assessment of disease activity VAS mm, and WOMAC pain subscale and total scores at 13 weeks. OA pain intensity, patients and physicians global assessment of disease activity, and WOMAC total and all subscale scores were analysed by visit as secondary variables. RESULTS: Lumiracoxib showed significant improvements in all primary and secondary variables compared with placebo. Lumiracoxib 200 mg od and celecoxib 200 mg od achieved similar improvements in OA pain intensity and functional status. Lumiracoxib 400 mg od demonstrated better efficacy for OA pain intensity and patients global assessment of disease activity at weeks 2, 4, and 8 and similar efficacy at week 13 compared with celecoxib 200 mg od. The incidence of adverse events AEs, serious AEs, and discontinuations due to AEs was similar in each group. CONCLUSION: Lumiracoxib demonstrated significant improvement in OA pain intensity, patients global assessment of disease activity, and the WOMAC pain subscale and total scores compared with placebo. Lumiracoxib was well tolerated in this study, with overall tolerability similar to that of placebo and celecoxib.

Adult↗
PubMed2004

The need for clinical guidance in the use of calcium and vitamin D in the management of osteoporosis: a consensus report.

A European Union (EU) directive on vitamins and minerals used as ingredients of food supplements with a nutritional or physiological effect (2002/46/EC) was introduced in 2003. Its implications for the use of oral supplements of calcium and vitamin D in the prevention and treatment of osteoporosis were discussed at a meeting organized with the help of the World Health Organization (WHO) Collaborating Center for Public Health Aspects of Rheumatic Diseases (Liège, Belgium) and the support of the WHO Collaborating Center for Osteoporosis Prevention (Geneva, Switzerland). The following issues were addressed: Is osteoporosis a physiological or a medical condition? What is the evidence for the efficacy of calcium and vitamin D in the management of postmenopausal osteoporosis? What are the risks of self-management by patients in osteoporosis? From their discussions, the panel concluded that: (1) osteoporosis is a disease that requires continuing medical attention to ensure optimal therapeutic benefits; (2) when given in appropriate doses, calcium and vitamin D have been shown to be pharmacologically active (particularly in patients with dietary deficiencies), safe, and effective for the prevention and treatment of osteoporotic fractures; (3) calcium and vitamin D are an essential, but not sufficient, component of an integrated management strategy for the prevention and treatment of osteoporosis in patients with dietary insufficiencies, although maximal benefit in terms of fracture prevention requires the addition of antiresorptive therapy; (4) calcium and vitamin D are a cost-effective medication in the prevention and treatment of osteoporosis; (5) it is apparent that awareness of the efficacy of calcium and vitamin D in osteoporosis is still low and further work needs to be done to increase awareness among physicians, patients, and women at risk; and (6) in order that calcium and vitamin D continues to be manufactured to Good Manufacturing Practice standards and physicians and other health care professionals continue to provide guidance for the optimal use of these agents, they should continue to be classified as medicinal products.

Aged↗
PubMed2004

Reduction in PINP, a marker of bone metabolism, with raloxifene treatment and its relationship with vertebral fracture risk.

In the Multiple Outcomes of Raloxifene Evaluation (MORE) trial, 7705 postmenopausal women with osteoporosis, defined by low bone mineral density and/or prevalent vertebral fractures (VF), were randomized to placebo or raloxifene (60 or 120 mg/day). All women received daily calcium (500 mg) and vitamin D (400-600 IU) supplements. Our previous analyses found that changes in BMD and biochemical markers of bone turnover are poorly predictive of the reduction in VF risk observed with raloxifene. This present study evaluated the effects of raloxifene on type I procollagen N-terminal propeptide (PINP), a new marker of bone turnover. Logistic regression analysis models evaluated the relationships between the changes at 1 year in PINP, serum osteocalcin (OC), bone-specific alkaline phosphatase (BSAP), and urinary excretion of type I collagen C-telopeptide fragments normalized to creatinine (CTx/Cr), and the risk of new VF at 3 years for placebo and pooled raloxifene. A subset of 967 women (mean age = 68 years) from the MORE cohort had PINP, OC, BSAP, and CTx evaluated at baseline. Both doses of raloxifene significantly decreased (P < 0.001) all biochemical markers of bone turnover from baseline. Compared to baseline, PINP levels were decreased by medians of 11.0% and 40.8% in the placebo and pooled raloxifene groups, respectively. In addition, the placebo and pooled raloxifene groups decreased serum OC by 8.5% and 31.8%, BSAP by 15.8% and 34.6%, and urinary CTx/Cr excretion by 5.6% and 46.5%, respectively, from baseline. In the pooled raloxifene group, the logistic regression relationship between 3-year VF risk and 1-year percentage change for each biochemical marker was statistically significant with PINP (slope estimate = 0.0085, P = 0.009), OC (slope estimate = 0.0068, P = 0.035), and BSAP (slope estimate = 0.0056, P = 0.039), but not with CTx/Cr (slope estimate = 0.0027, P = 0.192). Furthermore, the percent decrease in PINP at 1 year could account for 28% of the total reduction in vertebral fracture risk. In conclusion, a 1-year decrease in PINP, BSAP, or OC, but not CTx/Cr, may be predictive of the 3-year VF risk reduction with raloxifene therapy in this subset of postmenopausal women with osteoporosis.

Aged↗
PubMed2004

Validation and comparative evaluation of the osteoporosis self-assessment tool (OST) in a Caucasian population from Belgium.

BACKGROUND: Risk indices have been developed to identify women at risk of low bone mineral density (BMD) who should undergo BMD testing. AIM: To compare the performance of four risk indices in White ambulatory women in Belgium. DESIGN: Epidemiological cross-sectional study. METHODS: Records were analysed for 4035 postmenopausal White women without Paget's disease or advanced osteoarthritis, seen at an out-patient osteoporosis centre between January 1996 and September 1999. Osteoporosis risk index scores were compared to bone density T-scores. The ability of each risk index to identify women with low BMD (T-score < -2.0) or osteoporosis (T < -2.5) was evaluated. RESULTS: Using an Osteoporosis Self-Assessment Tool (OST) score <2 to recommend DXA referral, sensitivity ranged from 85% at the lumbar spine to 97% at the total hip to detect BMD T-scores of <or= -2.5, and specificity ranged from 34% at the total hip to 37% at the femoral neck and lumbar spine. The negative predictive value was high at all skeletal sites (89-99%), demonstrating the usefulness of the OST to identify patients who have normal BMD and should not receive DXA testing. All risk indices performed similarly, although the OST had somewhat better sensitivity and somewhat lower specificity than the other indices at the cut-offs evaluated. Among the 11-12% of women who were classified as highest risk using OST or the Osteoporosis Index of Risk (OSIRIS), 81-85% had low bone mass and 68-74% had osteoporosis. DISCUSSION: The performance of these risk indices among women in Belgium was similar to that reported earlier for other samples in Asian countries, the US, and the Netherlands. The OST and other risk indices are effective and efficient tools to help target high-risk women for DXA testing.

Absorptiometry, Photon↗
PubMed2004

Prevention of postmenopausal osteoporosis with pharmacological therapy: practice and possibilities.

Postmenopausal osteoporosis (PMO) is a common disease that will become more prevalent in the future, with costly implications for public health. Prevention of the disease and its consequences, namely fractures, is therefore, important for both the individual and society. This review discusses: the goals of PMO prevention; the identification of women at risk, including the use of bone mineral density and bone turnover markers; the relevance in the prevention setting of various current guidelines for PMO management; recent data on therapeutic options for the treatment and prevention of PMO, in particular bisphosphonates, hormone replacement therapy and several other new pharmacological agents. It concludes that it is crucial for PMO prevention to start before disease onset and that, in the light of recent evidence, the existing guidelines need updating if they are to continue to be relevant.

Anabolic Agents↗
PubMed2004

Time dependent risk of gastrointestinal complications induced by non-steroidal anti-inflammatory drug use: a consensus statement using a meta-analytic approach.

OBJECTIVES: To provide an updated document assessing the global, NSAID-specific, and time dependent risk of gastrointestinal (GI) complications through meta-analyses of high quality studies. METHODS: An exhaustive systematic search was performed. Inclusion criteria were: RCT or controlled study, duration of 5 days at least, inactive control, assessment of minor or major NSAID adverse effects, publication range January 1985 to January 2003. The publications retrieved were assessed during a specifically dedicated WHO meeting including leading experts in all related fields. Statistics were performed conservatively. Meta-regression was performed by regressing NSAID adjusted estimates against study duration categories. RESULTS: Among RCT data, indolic derivates provided a significantly higher risk of GI complications related to NSAID use than for non-users: RR = 2.25 (1.00; 5.08) than did other compounds: naproxen: RR = 1.83 (1.25; 2.68); diclofenac: RR = 1.73 (1.21; 2.46); piroxicam: RR = 1.66 (1.14; 2.44); tenoxicam: RR = 1.43 (0.40; 5.14); meloxicam: RR = 1.24 (0.98; 1.56), and ibuprofen: RR = 1.19 (0.93; 1.54). Indometacin users had a maximum relative risk for complication at 14 days. The other compounds presented a better profile, with a maximum risk at 50 days. Significant additional risk factors included age, dose, and underlying disease. The controlled cohort studies provided higher estimates: RR = 2.22 (1.7; 2.9). Publication bias testing was significant, towards a selective publication of deleterious effects of NSAIDs from small sized studies. CONCLUSION: This meta-analysis characterised the "compound" and "time" aspects of the GI toxicity of non-selective NSAIDs. The risk/benefit ratio of such compounds should thus be carefully and individually evaluated at the start of long term treatment.

Aged↗
PubMed2004

Type II collagen peptides for measuring cartilage degradation.

This paper describes two new immunoassays for a peptide of the triple helix of type II collagen (Coll 2-1) and its nitrated form (Coll 2-1 NO(2)). In healthy subjects aged between 20 and 65 years old, Coll 2-1 and Coll 2-1 NO(2) levels in serum were in means 125.13+/-3.71 and 0.16+/-0.08 nmol/l, respectively. These levels did not significantly vary with age. However, up to 45 years of age, Coll 2-1 NO(2) levels in women were significantly higher than in men. In patients with knee osteoarthritis (OA), Coll 2-1 in serum was found to be elevated compared to healthy controls (267.45+/-26.42 nmol/l vs 126.78+/-6.61 nmol/l). Further, we have demonstrated that an increase of the urinary levels of Coll 2-1 or Coll 2-1 NO(2) over 1 year was predictive of joint space narrowing progression in OA patients. In conclusion, these preliminary results indicate that Coll 2-1 could be a predictive marker of knee OA progression.

Adult↗
PubMed2003

Patient assessment using standardized bone mineral density values and a national reference database: implementing uniform thresholds for the reimbursement of osteoporosis treatments in Belgium.

Dual-energy X-ray absorptiometry (DXA) devices from the three main manufacturers provide different bone mineral density (BMD) values, due in part to technical differences in the algorithms for bone mineral content (BMC) and area measurements and in part to the use of different manufacturer-derived reference databases. As a result, significant differences exist between Hologic, Lunar and Norland systems in the reported young normal standard deviation scores or T-scores. In a number of European countries, including Belgium, a T-score below -2.5 is one of the key criteria for reimbursement of osteoporosis treatments. This paper addresses the first attempt to implement a nationwide, uniform expression of BMD in patients, in order to harmonize drug reimbursement. To this end, measures were taken to implement a uniform expression of BMD in Belgian patients, by converting each manufacturer's absolute BMD to standardized BMD (sBMD) values and by establishing a single national reference range.

Absorptiometry, Photon↗
PubMed2003

Relief in mild-to-moderate pain is not a confounder in joint space narrowing assessment of full extension knee radiographs in recent osteoarthritis structure-modifying drug trials.

OBJECTIVE: To assess whether improvement in knee pain biased the determination of the structure-modifying effect reported for glucosamine sulfate in two recent 3-year, randomised, placebo-controlled clinical trials, in which conventional standing antero-posterior full extension knee radiographs were used for the measurement of joint space narrowing, and in which pain relief might have improved knee full extension. DESIGN: Patients completing the 3-year treatment course were selected based on a WOMAC pain decrease at least equal to the mean improvement in the glucosamine sulfate arms in either of the original studies, irrespective of treatment with glucosamine sulfate or placebo (drug responders or placebo responders). In a second approach, 3-year completers were selected if their baseline standing knee pain (item #5 of the WOMAC pain scale) was 'severe' or 'extreme' and improved by any degree at the end of the trials. In both cases, changes in minimum joint space width were compared between treatment groups. RESULTS: Global knee pain was mild-to-moderate in the two study populations and in all patient subsets identified. There were obviously more pain improvers in the glucosamine sulfate subsets (N=76 in the two studies combined) than in the placebo subsets (N=57), but WOMAC pain scores improved to the same extent, which was as large as over 50% relative to baseline. Nevertheless, the placebo subsets in both studies underwent an evident mean (SD) joint space narrowing, which in the pooled analysis of both studies was -0.22 (0.80) mm, and was not observed with glucosamine sulfate: +0.15 (0.60) mm (P=0.003 vs placebo). Similar results were found in the smaller subsets with > or = severe baseline standing knee pain that improved after 3 years, with a joint space narrowing nevertheless of -0.28 (0.76) mm with placebo (N=26), not observed with glucosamine sulfate: +0.21 (0.68) mm (N=31; P=0.014 vs placebo). CONCLUSIONS: Knee pain relief did not bias the report of a structure-modifying effect of glucosamine sulfate in two recent long-term trials using conventional standing antero-posterior radiographs, possibly due to the mild-to-moderate patient characteristics.

Female↗
PubMed2003

Long-term efficacy of risedronate: a 5-year placebo-controlled clinical experience.

Limited placebo-controlled data are available to assess the long-term fracture efficacy of bisphosphonates. In order to determine the effects of 5 years of risedronate treatment, we extended a 3-year, placebo-controlled vertebral fracture study in osteoporotic women for an additional 2 years; women who entered the extension study continued to receive 5 mg risedronate or placebo according to the original randomization, with maintenance of blinding. End points included vertebral and nonvertebral fracture assessments, bone mineral density measurements, and changes in biochemical markers of bone turnover. A total of 265 women (placebo, 130; 5 mg risedronate, 135) entered the study extension and 220 (83%) completed the additional 2 years. Fracture results observed in the study extension were consistent with those observed in the first 3 years. The risk of new vertebral fractures was significantly reduced with risedronate treatment in years 4 and 5 by 59% (95% confidence interval, 19 to 79%, P = 0.01) compared with a 49% reduction in the first 3 years. Rapid and significant decreases in markers of bone turnover observed in the first 3 years were similarly maintained in the next 2 years of treatment. Increases in spine and hip bone mineral density that occurred in the risedronate group during the first 3 years were maintained or increased with a further 2 years of treatment. The mean increase from baseline in lumbar spine BMD over 5 years was 9.3% (P < 0.001). This study demonstrates that the effects of risedronate over 3 years on vertebral fracture and BMD are maintained with a further 2 years of treatment.

Aged↗
PubMed2003

Subchondral tibial bone mineral density predicts future joint space narrowing at the medial femoro-tibial compartment in patients with knee osteoarthritis.

Preliminary studies have shown that dual-energy X-ray absorptiometry (DXA) produces images of sufficient quality for a precise and accurate measurement at density of the subchondral bone. The objective of this study was to investigate the relationship between baseline subchondral tibial bone mineral density (BMD) and joint space narrowing observed after 1 year at the medial femoro-tibial compartment of the knee joint. Fifty-six consecutive patients, from both genders, with knee osteoarthritis diagnosed according to the American College of Rheumatology criteria, were included in the study. Radiographic posteroanterior views were taken, at baseline and after 1 year of follow-up. Minimum joint space width (JSW) measurement, at the medial femoro-tibial joint, was performed with a 0.1-mm graduated magnifying lens. Baseline BMD of the subchondral tibial bone was assessed by DXA. The mean +/- SD age of the patients was 65.3 +/- 8.7 years, with a body mass index of 28.0 +/- 4.9 kg/m(2). The minimum JSW was 3.5 +/- 1.5 mm and the mean BMD of the subchondral bone was 0.848 +/- 0.173 g/cm(2). There was a significant negative correlation between subchondral BMD and 1-year changes in minimum JSW (r = -0.43, p = 0.02). When performing a multiple regression analysis with age, sex, body mass index, and minimum JSW at baseline as concomitant variables, BMD of the subchondral bone as well as JSW at baseline were independent predictors of 1-year changes in JSW (p = 0.02 and p = 0.005, respectively). Patients in the lowest quartile of baseline BMD (<0.73 g/cm(2)) experienced less joint space narrowing than those in the highest BMD quartile (>0.96 g/cm(2)) (+0.61 +/- 0.69 mm versus -0.13 +/- 0.27 mm; p = 0.03). Assessment of BMD of the subchondral tibial bone is significantly correlated with future joint space narrowing and could be used as a predictor of knee osteoarthritis progression.

Absorptiometry, Photon↗
PubMed2003

Health-related quality of life and cost of ambulatory care in osteoporosis: how may such outcome measures be valuable information to health decision makers and payers?

The objective was to quantify the outcome of osteoporosis (OP) in terms of health-related quality of life (HR-QOL) and cost of ambulatory care and to look at the association between these two outcomes variables. A cross-sectional health survey of 4800 Belgian individuals over the age of 45 years was used. Individuals having reported OP were retrieved and for each of them, at least two matched individuals for age, sex, residency location, and health insurance status were identified. All individuals were assessed with the SF-36. The two major health insurance providers furnished cost value for ambulatory care. HR-QOL and cost data were compared between the OP group and control group. Beta-coefficients from linear regression were calculated to give information on the relative importance of the association between each SF-36 dimensions and cost of ambulatory care. Of 4796 individuals appropriately surveyed, 221 (4.8%) reported OP. The control group included 651 individuals. The OP group experienced impaired HR-QOL compared to their matched counterparts, all the difference in mean or median SF-36 scores being significant at the level of P < 0.001. Osteoporotic respondents averaged 816 in cost of ambulatory care whereas controls averaged 579 (P < 0.001). When looking at detailed comparisons between categories of cost, costs in the OP group far exceeded those in the control group, all the differences being significant at the level of P < 0.001 except for home health nurse (P = 0.012). In the OP group, vitality dimensions played the most important role in the determination of cost (beta = -0.28, P < 0.001), followed by physical functioning (beta = -0.26, P < 0.01), general health, and social functioning (beta = -0.23, P < 0.01). This study evidences the burden of OP in terms of HR-QOL and cost of ambulatory care. Exploring the association between HR-QOL and cost show that mental dimension such as vitality can play an important role in the determination of cost. Conclusively, they should not be neglected in future management of OP.

Aged↗
PubMed2003

Is there any rationale for prescribing hormone replacement therapy (HRT) to prevent or to treat osteoarthritis?

BACKGROUND: During the last two decades of the 20th century, hormone replacement therapy (HRT) has been considered as the sole pharmacological approach for counterbalancing or mitigating the effects of estrogens deprivation in post-menopausal women. Subsequently, HRT has been widely recommended for the management of chronic diseases occurring, in women during the second half of their life. The overall risk/benefit ratio of estrogens has been recently reassessed in the light of long-term prospective studies failing to demonstrate the expected benefit of HRT on cardiovascular diseases incidence. Osteoarthritis (OA) is one of the chronic conditions for which HRT has been suggested to provide beneficial outcomes. RESULTS: The presence of estrogen receptors in human cartilage is no longer debated. However, cellular or animal models of OA do not provide an unequivocal pathway for the influence of gonadal steroids on cartilage. Similarly, studies attempting to correlate serum or urinary levels of sex steroids to the onset or progression of OA gave conflicting results. No randomized, prospective, controlled trial was designed to specifically assess the impact of hormone replacement therapy on symptomatic or structural progression of OA. Large-scale observational studies or trials designed to assess other potential benefits of estrogens suggest that HRT use does not provide symptomatic relief in OA but may interfere with its long-term structural progression, particularly in the lower limbs. CONCLUSION: Based on the recent results of the Women Health Initiative suggesting that HRT health risks may outweigh benefits, one can hardly recommend, with the current level of evidence, HRT as a first-line treatment against progression of OA.

Cartilage, Articular↗
PubMed2003

Pharmacodynamics of follicle stimulating hormone (FSH) in postmenopausal women during pulsed estrogen therapy: Evidence that FSH release and synthesis are controlled by distinct pathways.

17 beta-Estradiol (E2) exerts negative feedback effects at the hypothalamo-pituitary level on serum FSH. This study investigated the effects of repeated daily administration of intranasal E2 (S21400) on the pharmacokinetics (PK) of E2 and estrone (E1) and the pharmacodynamics (PD) of FSH and assessed the PK/PD relationship between E2 and FSH using population model-dependent analysis. Postmenopausal volunteers (n = 24) received according to a balanced cross-over design, two 28-d treatments separated by a 2-month wash-out period: 300 microg E2, either alone or combined with oral dydrogesterone (20 mg/d) during the last 14 d of one of the treatments. Absorption of E2 was rapid, with maximal plasma concentrations at 10-30 min, returning to postmenopausal levels within 12 h. Over the 24-h period, FSH levels showed a U curve, with a minimum around 8 h after E2 administration. Moreover, over the treatment period, FSH basal values decreased by 17% between d 1 and 14 and an additional 5% between d 14 and 28. A PK/PD model described these short- and mid-term effects, possibly reflecting separate regulation mechanisms by E2 on FSH release and biosynthesis, respectively. The administration of progestin had no influence on E1, E2, and FSH model parameters. This study suggests that daily transient tissue exposure to E2 after pulsed estrogen therapy elicits short- and mid-term effects on the gonadotropin axis.

Administration, Intranasal↗