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Biomedical subjects

J Heikkinen

Publications and source records attributed to J Heikkinen.

At least 19 recordsLinked to original sources

Lifelong risk factors for osteoporosis and fractures in elderly women with low body mass index--a population-based study.

Low body weight is associated with an increased risk for osteoporosis and fractures, but the contribution of other lifestyle related factors have not been previously studied within lean elderly women. The present study evaluated the association between lifelong lifestyle factors and bone density, falls and postmenopausal fractures in elderly women with low body mass index (BMI). A population-based sample of 1,222 women aged 70 to 73 years was stratified by BMI tertiles, and all 407 women in the lowest tertile participated. Data on falls and postmenopausal fractures, physical activity, functional capacity, calcium intake, smoking, alcohol intake and medical factors at different ages were obtained by a questionnaire. Calcaneum bone mass as broadband ultrasound attenuation (BUA) was assessed with a quantitative ultrasound (QUS) device, and bone mineral density (BMD) at the distal radius was measured with a dual-energy X-ray absorptiometry (DXA). Low current physical activity was associated with lower calcaneum BUA and factors associated with higher BUA were body weight, low lifetime occupational physical activity, hormone replacement and type 2 diabetes. Weight, type 2 diabetes and thiatzide use were associated with higher radius BMD. The final multivariate model consisted of four independent factors associated with fractures: low lifetime habitual physical activity (OR 3.7, 95% CI 1.9-7.1), diabetes (OR 0.2, 95% CI 0.1-1.0), living alone (OR 1.7, 95% CI 1.0-3.0) and calcaneum BUA (1.8, 95% CI 1.3-2.4). Poor functional ability and symptoms of depression were associated with recent falling. In elderly women with low BMI, lifelong physical activity may protect from fractures, while low calcaneum bone mass and living unpartnered appear to be associated with an increased risk for fractures. Poor functional ability and presence of depression may be associated with risk of falling. Type 2 diabetes may modify the risk of low bone mass and low-trauma postmenopausal fractures. Albeit that the results of this study need to be confirmed in prospective follow-up studies, multifactorial program with the emphasis on physical and social activation in the primary care setting for preventing falls and fractures in lean elderly women is recommended.

Absorptiometry, Photon↗

Endometrial safety, overall safety and tolerability of transdermal continuous combined hormone replacement therapy over 96 weeks: a randomized open-label study.

OBJECTIVES: To establish whether transdermal continuous hormone replacement therapy (HRT) with estrogen/progestogen provides adequate long-term endometrial protection in postmenopausal women over a period of 96 weeks. METHODS: This multicenter, randomized, open-label, parallel-group study evaluated the endometrial effects and overall safety and tolerability of a transdermal matrix patch delivering estradiol (E2) 50 microg/day and norethisterone acetate (NETA) 140 microg/day (Estalis; patches applied twice weekly without intermediate breaks) and a once-daily oral comparator (Kliogest; one tablet containing E2 2 mg/NETA 1 mg) in postmenopausal women. A total of 406 women with an intact uterus, aged 44-69 years, were randomized in the 48-week core phase of the study, and 239 continued into the 48-week extension phase. Subjects were randomized in the ratio 3 : 1 to transdermal or oral E2/NETA treatment. RESULTS: No cases of endometrial hyperplasia or endometrial cancer were reported with either treatment during the core or extension phase. Both treatments were generally well tolerated, with most adverse events (>90%) being mild to moderate, although minor differences in the tolerability profile were observed between treatments. CONCLUSIONS: Continuous combined transdermal HRT with E2/NETA shows no evidence of an increased endometrial hyperplasia or endometrial cancer risk over a 96-week period.

Administration, Cutaneous↗

Feasibility of axillary ultrasound in the quality assessment of sentinel node biopsy in breast cancer surgery.

BACKGROUND AND AIMS: The purpose of this study was to evaluate the efficacy of high-resolution axillary ultrasound (AU) in detecting the rate of recurrence after a negative sentinel node (SN) biopsy in patients with breast cancer and without additional axillary dissection. MATERIALS AND METHODS: The operating oncologic surgeon performed 196 consequent sentinel node biopsies during surgery of breast cancer. The sentinel nodes were identified by using preoperative lymphoscintigraphy, intraoperative gamma probe and Patent Blue dye. A routine postoperative follow-up of the patients were performed every 3rd month including clinical examinations, blood chemistry and mammography. After 31 months (range 14-49 months), a high-resolution AU was performed for 107 patients with a negative sentinel node during surgery and without axillary dissection, to visualize any abnormal lymph nodes in the axilla. If necessary, large core biopsies were undertaken to obtain histology of abnormal axillary nodes. RESULTS: The SNs were visualized during preoperative lymphoscintigraphy in 167/196 (85%) and found during the surgery in 163/167 (98%) of patients. The mean number of removed SN were 1.7+/-0.8. The SN metastasis were found in 29% (56/196) of patients. During the follow-up, abnormal nodes were identified during AU in only 4/107 patients. Core biopsies confirmed benign histology in three patients and one case of lymphoma was detected. CONCLUSIONS: There were no axillary recurrences of breast cancer after a negative SN biopsy during the 2.6 year follow-up. Axillary ultrasound is a useful tool in the quality control of patients with negative SN biopsy and without diagnostic axillary dissection.

Axilla↗

Effect of endoscopic sinus surgery on antral mucociliary clearance.

Endoscopic sinus surgery (ESS) is the most used surgical approach in the treatment of chronic and recurrent maxillary rhinosinusitis. However, it still remains unclear how well surgery restores the mucociliary function in damaged maxillary sinus mucosa. There is also controversy whether to enlargen the natural ostium or not. We examined the mucociliary clearance (MCC) of maxillary sinuses in 27 patients with chronic and recurrent rhinosinusitis. On one side only an uncinectomy was done, on the contralateral side a middle meatal antrostomy was additionally performed. The mucociliary clearance (MCC) was measured in both sides preoperatively and 9 months after the operation. Measurements of the mucociliary clearance in maxillary sinuses were done using an isotope method. Preoperative mean residual activity on the uncinectomy side was 87.2 % and postoperative mean residual activity 94.1 %. On the middle meatal antrostomy side mean preoperative residual activity was 92.3 % and postoperative mean residual activity 88.4 %. Residual activity was considered as good (< or = 50 %) on the uncinectomy side in 2 sinuses (7.4 %) preoperatively and in 1 sinus (3.7 %) postoperatively. On the middle meatal antrostomy side residual activity was considered good in 1 sinus (3.7 %) preoperatively and in 4 sinuses (14.8 %) postoperatively. Mucociliary function remained poor even 9 months postoperatively. Surgery did not significantly improve the mucociliary function of maxillary sinus mucosa in chronic or recurrent rhinosinusitis. There was no statistical difference between operative techniques. In this study it seemed however, that uncinectomy combined with the enlargening of the natural ostium may restore maxillary sinus mucociliary clearance (MCC) better than uncinectomy alone.

Adult↗

Body size from birth to adulthood and bone mineral content and density at 31 years of age: results from the northern Finland 1966 birth cohort study.

The purpose of this study was to evaluate the association between body size from birth to adulthood and bone mineral content (BMC) and bone mineral density (BMD) at the age of 31 years in a longitudinal study of the Northern Finland birth cohort for 1966. Data were collected at birth, 1, 14, and 31 years. This analysis was restricted to a subsample of individuals (n =1,099) for whom the BMC (g) and BMD measurements (g/cm(2)) were performed on the distal and ultradistal radius by dual-energy X-ray absorptiometry (DXA) at the age of 31 years. Determinants of low BMC and BMD were analyzed using multivariate logistic regression. Growth retardation at birth, being underweight (BMI < or =20.0 kg/m(2)) at 31 years, and having a low calcium intake at 31 years were associated independently with low BMD at 31 years. Additionally, the proportion of subjects with low BMD was higher among those who had low standardized body weight (< or =1 SD) both at birth and at 14 years, and both at 14 and 31 years. Body weight at 31 years was the strongest associating factor of BCM at 31 years. Growth retardation at birth has long-lasting effects on adult bone mineral content and density of the distal and ultradistal radius independently of later body size, although adult body weight seems to be a most important determinant of BMC at the age of 31 years. Thinness and a low calcium intake are associated with low bone mineral content and density at 31 years of age. Further studies are needed to evaluate if these groups are at increased risk of osteoporosis in old age.

Absorptiometry, Photon↗

An additive edge correction for the influence potential of trees.

The influence potential on a quadrat (IPQ) is an index for measuring the ecological effect that trees have on understory vegetation observed in a quadrat of a plot. IPQ is defined as the sum of the effect of every trees in the plot, where the effect depends on the size of the tree and the distance between the tree and the quadrat. Since only the trees in the plot have been observed and not the trees outside the plot, the true IPQ may be underestimated. Existing edge corrections are not appropriate for this case. We propose a correction that consists of adding the expected IPQ due to effects of trees outside the plot to the observed IPQ. The expectation is obtained by applying the Campbell theorem for stationary marked point processes. Data from the 1985-86 National Forest Inventory of Finland was used to calculate IPQ for six quadrats systematically allocated to each of 1240 plots. The implementation of the correction for this data is described. The distributions of IPQ with and without the correction proved the existence of edge effects and the effectiveness of the correction to eliminate the bias. This method has the potential to be applied to other additive functions.

Agriculture↗

Bone mineral density and lipid changes during 5 years of follow-up in a study of prevention of breast cancer with toremifene in healthy, high-risk pre- and post-menopausal women.

A double-blind, randomised, placebo-controlled pilot study was initiated to evaluate the feasibility of chemoprevention with toremifene 60 mg/day in healthy women at high risk for breast cancer. Enrolment in the study was terminated earlier than planned because of slow patient accrual, although 13% of patients continued for 5 years. The revised efficacy outcomes were change in bone mineral density (BMD) from baseline at four skeletal sites, plus effects on serum lipids. In premenopausal women there was a trend for sustained increase in BMD during toremifene therapy after year 1 in lumbar spine. In postmenopausal women, toremifene had little or no effect on BMD trends. Levels of total and low-density lipoprotein (LDL) cholesterol were largely unchanged from baseline in premenopausal women treated with toremifene but were often slightly lower than in the placebo group during follow-up. Total and LDL cholesterol levels declined slightly from baseline in the postmenopausal women and were, at several points during the first 3 years, significantly lower than in the corresponding placebo group (p < 0.01). We conclude that: (a) assessment of toremifene 60 mg/day in chemoprevention will require further clinical trials; (b) toremifene 60 mg/day has no substantive negative effects on BMD in pre- or postmenopausal women and may exert a minor favourable influence (in particular, the effects of toremifene 60 mg/day on BMD in premenopausal women may make the drug an attractive alternative to tamoxifen 20 mg/day for that patient subset); (c) lipid effects of toremifene 60 mg/day are, at minimum, neutral and may be modestly favourable for reducing cardiovascular risk.

Adult↗

Successful treatment of osteitis pubis by using totally extraperitoneal endoscopic technique.

Osteitis pubis is characterized by pain, inflammation, and sclerosis in the pubic symphysis. It is often a self-limiting disease in athletes, but persistent pain may occasionally need surgery. Video-assisted placement of extraperitoneal retropubic synthetic mesh to support the damaged area may hasten the healing of this injury. During 1997 - 2002 five elite level male athletes with chronic groin pain associated with osteitis pubis were operated. The diagnosis was based on clinical findings, x-ray, magnetic resonance imaging (MRI), and isotope bone scanning. A 10 x 15 cm polypropylene mesh was placed into preperitoneal retropubic space using video-assisted technique. The pain and return to sport were asked at 1, 6, and 12 months after surgery. Preoperative technetium bone scan revealed an enhanced isotope uptake of pubic bone in each patient. T2-weighted MRI (n = 3) indicated bone marrow edema, which was decreased postoperatively on repeated MRI scans. Periosteal edema and irritation were also seen at operation. No complications were associated with the insertion of mesh. All 5 athletes returned to their sport activities between one to two months after surgery. After one year, no tenderness or pain was observed in the pubic bone. When conservative treatment fails, the placement of retropubic mesh is safe and a mini-invasive method to hasten the rehabilitation of osteitis pubis in selected cases. The postoperative recovery was uneventful, and the patients returned rapidly to their sporting activities.

Adult↗

CD4+ CD25+ T cells with the phenotypic and functional characteristics of regulatory T cells are enriched in the synovial fluid of patients with rheumatoid arthritis.

CD4(+) CD25(+) regulatory T (T(reg)) cells play a critical role in the maintenance of peripheral tolerance and the prevention of autoimmunity. In the present study, we have explored the characteristics of CD4(+) CD25(+) T(reg) cells in patients with rheumatoid arthritis (RA). The frequency and phenotype of CD4(+) CD25(+) T cells in paired samples of synovial fluid (SF) and peripheral blood (PB) from patients with RA and PB from normal controls were analysed. An increased frequency of CD4+ cells T cells expressing CD25 was detected in SF compared to PB from patients with RA. No significant difference was observed in the numbers of CD4(+) CD25(+) T cells in PB from patients and controls. SF CD4(+) CD25(+) T cells expressed high levels of CTLA-4 (both surface and intracellular), GITR and OX40, as well as Foxp3 transcripts. Functionally, SF CD4(+) CD25(+) T cells were impaired in their proliferative responses and could suppress the proliferation of their CD4(+) CD25(-) counterparts. In conclusion, these data demonstrate that CD4(+) CD25(+) T(reg) cells, with the potential to regulate the function of effector T cells and antigen-presenting cells, accumulate in the synovium of patients with RA.

Adult↗

Decreased bone mineral density and content in neurofibromatosis type 1: lowest local values are located in the load-carrying parts of the body.

Neurofibromatosis type 1 (NF1) is a dominantly inherited disease. Skeletal ailments such as short stature, kyphoscoliosis, tibial bowing and pseudarthrosis are common osseous manifestations of NF1. Previously, a correlation with scoliosis and decreased bone mineral density (BMD) of the lumbar spine has been reported in 12 NF1 patients. A total of 35 NF1 patients and 26 healthy controls were included in the present study. Of the participants over 20 years of age (26 NF1 patients and all controls) 14 were male and 12 were female, seven of whom were premenopausal. The controls were matched for age, sex and body mass index (BMI). Physical activity and medical history of NF1 patients were evaluated to screen the fractures and osseous manifestations of the disease and to rule out the factors that effect BMD. BMD and bone mineral content (BMC) were measured with DXA, using a total body program. The present study detected a lowered bone mineral density (p =0.028) and content (p <0.001) in NF1 patients of both sexes. The results of the present study also show that NF1 patients have an increased risk for osteoporosis. Among NF1 patients seven cases of osteoporosis and 13 cases of osteopenia were detected. In controls, one case of osteoporosis and 13 cases of osteopenia were detected. The location of the lowest local BMD was clustered to the load-carrying parts of the body in NF1 patients. Physical activity and the medical history of the NF1 patients did not explain the decreased BMD and BMC. The findings of the present and previous studies suggest that the pathogenesis of the osseous manifestations in NF1 may involve impaired development of the skeletal system and impaired maintenance of bone structure.

Absorptiometry, Photon↗

Effects of ospemifene, a novel SERM, on biochemical markers of bone turnover in healthy postmenopausal women.

Ospemifene is a novel selective estrogen receptor modulator (SERM). Here we studied the effects of ospemifene on bone turnover in postmenopausal women. This was a randomized, double-blind study in which 159 healthy postmenopausal women received 30 (n = 40), 60 (n = 40) or 90 mg (n = 40) of ospemifene or placebo (n = 39) for 3 months. Bone resorption was assessed by measuring the urinary outputs of N- and C-terminal crosslinking telopeptides of type I collagen (NTX and CTX, respectively). Bone formation was assessed by measuring the levels of procollagen type I N propeptide (PINP), procollagen type I C propeptide (PICP), and bone-specific alkaline phosphatase (bone ALP) in serum. All markers were studied at baseline, 3 months, and 2-4 weeks after cessation of the medication. Ospemifene decreased bone resorption dose-dependently, as seen from falls in NTX by 6.1, 9.4 and 12.9% in the 30, 60 and 90 mg ospemifene groups, respectively (p < 0.05 for all dose levels when compared to placebo). CTX values decreased in the 90 mg ospemifene group by 4.8% (p < 0.05). A dose-dependent decrease was also observed in the bone formation markers: PINP values decreased by 9.8 (p < 0.05) and 15.3% (p < 0.01), and PICP values by 12.0 and 11.9% in the 60 and 90 mg ospemifene groups, respectively. Bone ALP decreased in 60 and 90 mg ospemifene groups by 1.9 and 2.6%, respectively (p < 0.05 for both dose levels when compared to placebo). These results show that ospemifene is effective in reducing bone turnover in postmenopausal women.

Alkaline Phosphatase↗

A low-dose start in hormone replacement therapy provides a beneficial bleeding profile and few side-effects: randomized comparison with a conventional-dose regimen.

OBJECTIVE: To compare bleeding control, efficacy and safety of two dose-ranging continuous combined hormone replacement therapy (HRT) regimens with those of a conventional continuous combined HRT. METHODS: An open, 2-year, multicenter study was conducted in 393 postmenopausal women recruited from 16 study sites. The women were randomized to three continuous combined HRT regimens. One group (n = 131) started with 1 mg of estradiol valerate (E2V) plus 2.5 mg of medroxyprogesterone acetate (MPA), the second group (n = 130) received 1 mg E2V + 5 mg MPA and the third (n = 132) 2 mg estradiol (E2) and 1 mg norethisterone acetate (NETA). In the two E2V/MPA groups the initial E2V dose of 1 mg was increased to 2 mg after six cycles (one cycle = 28 days) to evaluate the effect of dose increase on bleeding control. RESULTS: The E2V/MPA regimens with a lower estrogen dose induced less bleeding and other adverse effects during the first six cycles than did the E2/NETA regimen. Bleeding disturbances and breast tenderness resulted in significantly more discontinuations in the E2/NETA group. After the estrogen dose increase in the E2V/MPA regimens, all groups showed comparable bleeding patterns and adverse effect profiles. The lower E2V dose was as effective as standard-dose E2 in relieving climacteric symptoms. All regimens provided excellent endometrial safety. No hyperplasias were reported. CONCLUSIONS: Continuous combined HRT should be started, and continued, with the lowest effective doses. An increase of the estrogen dose is recommended only if the initial dose is not sufficient for symptom control.

Aged↗

Phenotypic characterization of regulatory T cells in the human decidua.

Pregnancy is a unique situation for the maternal immune system. We have studied and identified a CD4+CD25+ regulatory T (Treg) cell population isolated from the human decidua. This mucosal surface in the uterus is in direct contact with semiallogenic fetal cells. We observed that about 14% of the decidual CD4+ T cells have the CD4+CD25+ phenotype. The decidual CD4+CD25+ T cells expressed high frequency of intracellular CTLA-4 (CTLA-4i). The majority of CD4+CD25+CTLA-4i+ cells were also positive for GITR and OX40, typical markers for human Treg cells. The frequency of CD4+CD25+ T cells in the peripheral blood from pregnant women was found to be increased during the first and second trimester of gestation when compared to nonpregnant controls. Being an important molecule for Treg cells, the role of CTLA-4 in the regulation of indoleamine 2,3-dioxygenase (IDO) expression was also examined. The stimulation with CTLA-4Ig did not increase IDO mRNA expression in CD14+ cells from pregnant women, while IFN-gamma was observed to up-regulate IDO expression. The presence of Treg cells in the human decidua suggests that these cells are important in protecting the fetus from alloreactive immune responses at the maternal-fetal interface.

Adult↗

Lifestyle factors are associated with osteoporosis in lean women but not in normal and overweight women: a population-based cohort study of 1222 women.

The aim of the present population-based cohort study was to evaluate the contribution of lifelong lifestyle factors to calcaneal and distal forearm bone mass in elderly women. We studied 1222 of the 1689 eligible home-dwelling women aged 70-73 years. Lifelong occupational and leisure time physical activity, calcium intake, smoking, alcohol intake and medical history were obtained by a self-completed questionnaire. Main outcome measures were broadband ultrasound attenuation (BUA) of the calcaneus and bone mineral density (BMD) of the radius measured once in 1997-1998. The women with BMI < or = 25.1 kg m(2) had lower BUA (p < 0.0001) and radial BMD values (p < 0.0001) than women with higher BMI. Lifestyle factors associated with BUA in the leanest women were: low physical activity at work (RR 0.4; 95% confidence interval 0.2 to 0.8), low habitual exercise at the ages 30 years, 50 years and currently (RR 1.5; 1.0 to 2.4; RR 1.5; 1.1 to 2.6; RR 1.7; 1.1 to 2.7), poor mobility (RR 1.9; 1.2 to 3.0), coffee intake > or = 5 cups/day (RR 1.7; 1.1 to 2.7), type 2 diabetes (RR 0.3; 0.1 to 0.9) and hypertension (RR 0.5; 0.3 to 0.8). Type 2 diabetes protected lean women from lower distal and ultradistal radial bone density (RR 0.3; 0.1 to 0.8; RR 0.1; 0.1 to 0.5). The selected lifestyle factors were not associated with lowered calcaneal or radial bone density in the higher categories of BMI. In conclusion, risk factors for lower calcaneal and radial bone density appear to be different among lean and normal/obese women. Lifelong recreational physical activity, low physical activity at work, type 2 diabetes and hypertension seem to be associated with increased bone density, while high coffee intake may increase the risk of lower bone density in lean elderly women. These factors are potentially modifiable, and intervention studies targeted at this risk category of women are needed.

Aged↗

Phenotypic characterization of human decidual macrophages.

Pregnancy is a challenge to the immune system, which not only has to protect the mother and the fetus from invading pathogens but to also maintain immunological tolerance against the fetus. However, the mechanisms inhibiting local immune responses in the maternal decidual tissue are poorly understood. We have studied decidual CD14+ macrophages, which may be important in the maintenance of a tolerance against the developing fetus. Decidual macrophages expressed HLA-DR, but lower levels of costimulatory molecule CD86 than peripheral blood CD14+ monocytes from pregnant and non-pregnant women. Decidual macrophages produced spontaneously high levels of interleukin-10. Our findings suggest that decidual macrophages could represent an inhibitory type of APCs. Supporting this conclusion indoleamine 2,3-dioxygenase (IDO), suggested to have an immunosuppressive role in pregnancy, was expressed in decidual macrophages. Furthermore, decidual macrophages were not able to differentiate into dendritic cells under the influence of IL-4 + GM-CSF. These results suggest an immunoinhibitory function of decidual macrophages at the maternal-fetal interface.

Antigen Presentation↗

Nosocomial Legionella pneumophila serogroup 5 outbreak associated with persistent colonization of a hospital water system.

An outbreak of infections caused by Legionella pneumophila serogroup 5 was detected in a university hospital, and nosocomial reservoirs of the legionella epidemic were examined. Clinical isolates from two patients who had been affected by the L. pneumophila serogroup 5 outbreak, and from another patient with a legionella infection caused by the same serogroup 3 years later, were compared to L. pneumophila serogroup 5 isolates from the hospital water supply by two molecular methods, amplified fragment length polymorphism (AFLP) analysis and random amplified polymorphic DNA analysis (RAPD). Genotyping confirmed the epidemiological linkage of the first two patients, and linked their infections with the hospital water supply. The third clinical strain, which was also linked to the hospital water, was very similar to the epidemic strain. Even though the water distribution system was sanitized (superheat and flush sanitation), the epidemic strain was shown to be persisting in the hospital water outlets several years after its initial discovery.

Adult↗

Ultrasonic depolymerization of aqueous polyvinyl alcohol.

Ultrasonication has proved to be a highly advantageous method for depolymerizing macromolecules because it reduces their molecular weight simply by splitting the most susceptible chemical bond without causing any changes in the chemical nature of the polymer. Most of the effects involved in controlling molecular weight can be attributed to the large shear gradients and shock waves generated around collapsing cavitation bubbles. In general, for any polymer degradation process to become acceptable to industry, it is necessary to be able to specify the sonication conditions which lead to a particular relative molar mass distribution. This necessitates the identification of the appropriate irradiation power, temperature, concentration and irradiation time. According to the results of this study the reactors constructed worked well in depolymerization and it was possible to degrade aqueous polyvinyl alcohol (PVA) polymer with ultrasound. The most extensive degradation took place at the lowest frequency used in this study, i.e. 23 kHz, when the input power was above the cavitation threshold and at the lowest test concentration of PVA, i.e. 1% (w/w). Thus this study confirms the general assumption that the shear forces generated by the rapid motion of the solvent following cavitational collapse are responsible for the breakage of the chemical bonds within the polymer. The effect of polymer concentration can be interpreted in terms of the increase in viscosity with concentration, causing the molecules to become less mobile in solution and the velocity gradients around the collapsing bubbles to therefore become smaller.

Journal Article↗

Effects of peroral and transdermal oestrogen replacement therapy on glucose and insulin metabolism.

OBJECTIVE: Conflicting data have been reported previously on the effects of oestrogen replacement therapy on glucose tolerance, and the effects on glycosylated haemoglobin GHbA(1c) have been studied only among diabetics. The objective of this study was to evaluate the effects on glucose and insulin metabolism among nondiabetic women and to compare the outcomes of peroral and transdermal modes of administration. DESIGN: The effects of peroral oestradiol valerate 2 mg/day with placebo gel were compared to those of transdermal 17 beta-oestradiol gel (1 mg oestradiol/day) and placebo tablets in a randomised, double-blind, double-dummy study for six months. PATIENTS: Seventy-nine hysterectomised, nondiabetic postmenopausal women, 39 women in the peroral oestrogen group and 40 in the gel group. MEASUREMENTS: Oral glucose tolerance tests (OGTT) with blood glucose, serum C-peptide and insulin determinations were performed. GHbA(1c), IGF-I and IGFBP-1 were measured at baseline and after six months of therapy. In addition, insulin sensitivity and insulin secretion indices were obtained from OGTT. RESULTS: A small significant reduction in the GHbA(1c) concentration was observed during both peroral (P < 0.05) and transdermal oestrogen therapy (P < 0.05). However, no effect on insulin sensitivity was observed. The response to a standard 75 g oral glucose load was similar in the study groups. Compared with the baseline values, the area under the curve for C-peptide decreased by 8% both in the peroral group (P < 0.05) and in the gel group (P < 0.01). The fasting and postchallenge glucose and insulin levels or insulin release indices were not significantly altered. Peroral oestrogen decreased IGF-I and increased IGFBP-1, but these findings were not associated with the changes in glucose metabolism. CONCLUSIONS: Neither peroral nor transdermal oestradiol replacement therapy seemed to induce any negative effects on glucose metabolism over a time period of 6 months.

Administration, Cutaneous↗