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1.
COMPARISON OF VITAMIN D REPLACEMENT STRATEGIES WITH HIGH-DOSE INTRAMUSCULAR OR ORAL CHOLECALCIFEROL: A PROSPECTIVE INTERVENTION STUDY.
Masood, MQ, Khan, A, Awan, S, Dar, F, Naz, S, Naureen, G, Saghir, S, Jabbar, A
Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists. 2015;(10):1125-33
Abstract
OBJECTIVE To ascertain the frequency of correction of vitamin D deficiency (VDD) with single or multiple doses of oral (p.o.) and intramuscular (i.m.) administration of 2 high-dose preparations of vitamin D3 (VD3). METHODS This was a prospective intervention study conducted in an ambulatory care setting. One hundred participants with VDD (25-hydroxy vitamin D [25-OHD] <20 ng/mL) were randomized to receive a dose of 600,000 or 200,000 IU of VD3 via a p.o. or i.m. route. The main outcome measure was serum 25-OHD levels at 2, 4, and 6 months after the intervention. The same dose was repeated in participants if 25-OHD remained <30 ng/mL at 2 and 4 months. RESULTS At 2 months, VDD was corrected in 93.8% of participants in Group 1 (600,000 IU i.m.); 83.3% in Group 2 (600,000 IU p.o.), 87.5% in Group 3 (200,000 IU i.m.), and 70.6% in Group 4 (200,000 IU p.o.). The mean changes from baseline in vitamin D levels at 2 months were 29.6 ± 13.7, 19.8 ± 12.3, 18.3 ± 10.6, and 13.7 ± 7.8 ng/mL in Groups 1, 2, 3, and 4, respectively. The mean levels remained significantly higher from baseline in all groups at all time points during the 6 months of observation. The mean 25-OHD level achieved in Group 1 was significantly higher than all other groups at 6 months. CONCLUSION Two months after the intervention, VDD was corrected in more than 70% of participants with a single dose of either 600,000 or 200,000 IU given p.o. or i.m.
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2.
Metabolic syndrome and the effect of testosterone treatment in young men with congenital hypogonadotropic hypogonadism.
Sonmez, A, Haymana, C, Bolu, E, Aydogdu, A, Tapan, S, Serdar, M, Altun, B, Barcin, C, Taslipinar, A, Meric, C, et al
European journal of endocrinology. 2011;(5):759-64
Abstract
OBJECTIVE The relationship between metabolic syndrome (MS) and hypogonadism has always been investigated in study groups confounded with aging, obesity or chronic metabolic disorders. So far, there has been no data about the presence of MS in young hypogonadal patients. Also, there is controversial data about the metabolic effects of testosterone replacement therapy. We investigated the frequency of MS in treatment-naïve, young men with congenital hypogonadal hypogonadism (CHH). We also searched for the effect of testosterone replacement on the metabolic profiles of this specific patient group. DESIGN Retrospective analysis. METHODS A total of 332 patients (age 21.68 ± 2.09 years) were enrolled. The control group included 395 age- and body mass index (BMI)-matched healthy young men (age 21.39 ± 1.49 years). Standard regimen of testosterone esters (250 mg/3 weeks) was given to 208 patients. RESULTS MS was more prevalent in CHH (P<0.001) according to healthy controls. The patients had higher arterial blood pressure, waist circumference (WC), triglyceride (P<0.001 for all), fasting glucose (P=0.02), fasting insulin (P=0.004), homeostatic model assessment of insulin resistance (HOMA-IR) (P=0.002) and lower high density lipoprotein (HDL) cholesterol (P<0.001) levels. After 5.63±2.6 months of testosterone treatment, the BMI, WC (P<0.001 for both), systolic blood pressure (P=0.002) and triglyceride level (P=0.04) were increased and the total and HDL cholesterol levels were decreased (P=0.02 and P<0.001 respectively). CONCLUSIONS This study shows increased prevalence of MS and unfavorable effects of testosterone replacement in young patients with CHH. Long-term follow-up studies are warranted to investigate the cardiovascular safety of testosterone treatment in this specific population.
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3.
A new hormone replacement therapy containing a progestogen with anti-mineralocorticoid activity.
Stevenson, JC
The journal of the British Menopause Society. 2006;:8-10
Abstract
Drospirenone is a new progestogen in hormone replacement therapy, with anti-mineralocorticoid activity. This anti-mineralocorticoid activity counteracts water and sodium retention, helping to reduce the likelihood of fluid retention that some women experience with hormone replacement therapy. In a post hoc analysis of women with mild hypertension, estradiol (1 mg) plus drospirenone (2 mg) was found to lower blood pressure in mildly hypertensive women. The introduction of estradiol plus drospirenone may offer the opportunity to re-evaluate the contribution of the progestogen component of hormone replacement therapy.
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4.
Changes in prothrombin and activated partial thromboplastin time during replacement therapy with human recombinant growth hormone in growth hormone deficient adults.
Miljic, D, Miljic, P, Doknic, M, Pekic, S, Djurovic, M, Colovic, M, Popovic, V
Hormones (Athens, Greece). 2006;(3):187-91
Abstract
BACKGROUND In rodents, Growth Hormone (GH) has been shown to stimulate coagulation parameters, including Prothrombin Time (PT), activated Partial Thromboplastin Time (aPTT) and vitamin K dependent coagulation factors. However, there are no reports on the influence of GH replacement therapy on global coagulation tests in Growth Hormone Deficiency (GHD). OBJECTIVE The aim of this study was to investigate the effects of GH administration on basic coagulation parameters: PT, aPTT and fibrinogen concentrations in adult GHD patients before and during one year of GH replacement. DESIGN Twenty-one adult patients with severe GHD (mean age +/- SE: 38.6 +/- 2.8 years) were included in this hospital based, prospective, interventional study. All patients were treated with rhGH for 12 months (GH dose: 0.4 mg/day for male and 0.6 mg/day for female patients). IGF-1 concentrations were determined using RIA-INEP kits. Basic coagulation tests, i.e. aPTT and fibrinogen concentrations, were measured before and after 3, 6 and 12 months of treatment with rhGH. Control values were obtained from fourteen "healthy" subjects matched by age, sex and body mass index (BMI). RESULTS At baseline, we observed no significant differences in PT, aPTT and fibrinogen values between GHD and healthy subjects. IGF-1 concentrations increased significantly within 3 months of GH therapy (8.2 +/- 1.5 vs. 24.2 +/- 2.9 nmol/l, p <0.05) and remained stable thereafter. A significant increase in PT values, which was more pronounced in female subjects, was noted after 6 and 12 months of treatment with GH. aPTT values increased significantly after 12 months of treatment only in male patients (28.8 +/- 4.6 vs. 39.7 +/- 2.1 s.; p <0.05). No significant changes in fibrinogen concentrations were found during the study. CONCLUSIONS Twelve months of GH replacement therapy led to a significant increase in PT and aPTT values in adult GHD patients, while fibrinogen concentrations did not change. Changes in PT were more pronounced in female GHD patients, while an increase in aPTT values was observed only in male patients with GHD. The clinical significance of these changes needs further evaluation.
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5.
Treatment adherence in the Estonian postmenopausal hormone therapy (EPHT) trial [ISRCTN35338757].
Vorobjov, S, Hovi, SL, Veerus, P, Pisarev, H, Rahu, M, Hemminki, E
Maturitas. 2005;(3-4):286-95
Abstract
OBJECTIVE To investigate treatment adherence and factors related to non-adherence in the Estonian postmenopausal hormone therapy (EPHT) trial. METHODS A total of 1823 postmenopausal women aged 50-64 years were recruited into the EPHT trial from 1999 to 2001. They were randomised into the blind group receiving continuous orally administered postmenopausal hormone therapy (PHT) or a placebo and to a non-blind group receiving open-label PHT or no drugs. A woman was classified as non-adherent, if she had stopped treatment for at least 6-month period in treatment arms or used PHT for at least 6-month period in the control group. Adherence was calculated by the Kaplan-Meier method, and factors affecting adherence were studied with Cox proportional hazard modelling. RESULTS The rate of adherent women declined approximately 50% during the first year in all treatment arms. Less than 10% of the control group women started taking prescribed PHT. Older women, with lower education, with only one birth, never used oral contraceptives (OC), with lower physical activity or who were dissatisfied with the information received from the trial staff, were more likely to discontinue. In treatment arms, the two most often cited reasons for non-adherence were side-effects and woman's loss of interest in participation. Control group women started PHT due to the menopausal symptoms or on doctor's recommendation. CONCLUSIONS The adherence was similar to that found for PHT use in everyday life. Higher adherence was related to younger age, higher education, previous OC use, physical activity and satisfaction with received information.
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6.
Significant differential effects of lower doses of hormone therapy or tibolone on markers of cardiovascular disease in post-menopausal women: a randomized, double-blind, crossover study.
Koh, KK, Han, SH, Shin, MS, Ahn, JY, Lee, Y, Shin, EK
European heart journal. 2005;(14):1362-8
Abstract
AIMS: We have previously reported that lower doses of hormone therapy (L-HT) and tibolone have different effects on markers of cardiovascular disease when compared with conventional doses of HT. The objective was to compare the effects of L-HT and tibolone on lipid profile, vasodilation, and factors associated with inflammation and haemostasis. METHODS AND RESULTS Forty-one women received a combination of micronized progesterone 100 mg with conjugated equine estrogen 0.3 mg vs. tibolone 2.5 mg alone daily in random order during 2 months with 2 months washout period. When compared with L-HT, tibolone significantly reduced total cholesterol (P<0.001), triglyceride (P<0.001), HDL cholesterol (P<0.001) levels, and triglyceride/HDL cholesterol ratios (P=0.004) except total cholesterol/HDL cholesterol ratios. Tibolone improved flow-mediated response to hyperaemia from baseline values (P<0.001) by a similar magnitude to L-HT. L-HT and tibolone did not increase high-sensitivity C-reactive protein relative to baseline values. L-HT reduced antithrombin III from baseline values (P=0.037), compared with tibolone showing no changes. However, there was no difference between either. In contrast, tibolone increased pro-thrombin fragment 1+2 (F1+2) from baseline values (P=0.002), compared with L-HT showing no changes. Tibolone significantly reduced plasma plasminogen activator inhibitor type 1 (PAI-1) antigen levels from baseline values (P=0.004), compared with L-HT showing no changes. The effects of L-HT and tibolone on F1+2 and PAI-1 were significantly different (P=0.045 and P=0.008, respectively). CONCLUSION Both tibolone and L-HT improved flow-mediated response by a similar magnitude and did not significantly increase high-sensitivity C-reactive protein. However, tibolone significantly reduced PAI-1, but increased F1+2 more than L-HT.
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7.
Vitamin A and iron supplementation is as efficient as hormonal therapy in constitutionally delayed children.
Zadik, Z, Sinai, T, Zung, A, Reifen, R
Clinical endocrinology. 2004;(6):682-7
Abstract
OBJECTIVE To assess the effect of nutritional supplementation on growth and puberty in constitutionally delayed children. PATIENTS One hundred and two boys, 13.6-15.5 years of age, who were referred because of short stature and delayed puberty. METHODS The boys were randomly allocated to one of the following treatment groups: oxandrolone therapy, 5 mg/day for 6 months (n = 15), testosterone depot, 100 mg monthly for 3 months (n = 15) or for 6 months (n = 20), nutritional programme (n = 17), oxandrolone and nutritional programme (n = 15) or passive observation (n = 20). Boys in the nutritional programmes received 12 mg/day iron and 6000 IU/week of vitamin A. Outcome measurements were of height, weight, pubertal signs, dietary intake, serum vitamin A, iron, GH and IGF-1. RESULTS Six months of vitamin A supplementation induced growth acceleration similar to that seen in the oxandrolone- and testosterone-treated children, and significantly greater than in the observation group (9.3 +/- 2.9 vs. 4.0 +/- 0.9 crn/yr, P < 0.001). Whereas in the vitamin A-supplemented group, puberty (increase in testicular volume ≥ 12 ml) was induced within 12 months. In all testosterone-treated patients, pubic hair was noted within 3 months and a testicular volume of ≥ 12 ml was observed 9-12 months after the initiation of therapy. No pubertal signs were noted in the observation group during this time. CONCLUSIONS Subnormal vitamin A intake is one of the aetiological factors in delayed pubertal maturation. Supplementation of both vitamin A and iron to normal constitutionally delayed children with subnormal vitamin A intake is as efficacious as hormonal therapy in the induction of growth and puberty.
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Effects of oral and transdermal 17 beta-estradiol combined with progesterone on homocysteine metabolism in postmenopausal women: a randomised placebo-controlled trial.
Lacut, K, Oger, E, Abalain, JH, Moineau, MP, Mottier, D, ,
Atherosclerosis. 2004;(1):173-80
Abstract
Mild hyperhomocysteinemia is a risk factor for both ischaemic heart disease and venous thromboembolism. The effects of transdermal estrogen replacement therapy (ERT) on homocysteine metabolism in postmenopausal women have scarcely been investigated. This clinical trial aimed to estimate the effects of combined hormone replacement therapy on the fasting total homocysteine levels according to the estrogen route of administration. We enrolled 196 postmenopausal women, who were randomly allocated to receive on a continuous basis either 1mg of 17 beta-estradiol orally (n = 63) or 50 microg transdermally (n = 68) per day, both combined with a daily intake of 100 mg progesterone, or placebo (n = 65) over a period of 6 months. Neither oral nor transdermal ERT significantly affected total plasma homocysteine levels or red-blood cell folate levels. However, oral ERT significantly decreased plasma vitamin B12 levels compared to placebo (mean relative variation difference over 6 months between oral ERT and placebo: -11.7% (95%CI, -21 to -2%) whereas transdermal ERT did not display any significant effects. Our data show that transdermal ERT as well as low dose of oral ERT does not significantly affect the homocysteine metabolism. This finding does not support a role for transdermal estrogen in the prevention of ischaemic heart disease in postmenopausal women.
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9.
Conventional glucocorticoid replacement overtreats adult hypopituitary patients with partial ACTH deficiency.
Agha, A, Liew, A, Finucane, F, Baker, L, O'Kelly, P, Tormey, W, Thompson, CJ
Clinical endocrinology. 2004;(6):688-93
Abstract
BACKGROUND Glucocorticoid therapy is associated with potentially serious side-effects, but there is no information available regarding glucocorticoid requirement in adult hypopituitary patients with partial ACTH deficiency. SUBJECTS Ten male adult hypopituitary patients with partial ACTH deficiency, baseline plasma cortisol > 200 nmol/l but a peak stimulated cortisol < 500 nmol/l and 10 matched healthy male control volunteers participated. DESIGN Patients were assigned, in a random order, to a cross-over protocol of treatment for 1 week with full dose hydrocortisone (10 mg twice daily), half-dose hydrocortisone (5 mg twice daily), or no treatment. All patients completed all three of the treatment limbs. MEASUREMENTS Following each treatment schedule, patients underwent an 11-h cortisol day curve (CDC), and the results were compared with those from the 10 control volunteers on no glucocorticoid treatment. RESULTS The integrated CDC values were significantly higher in patients taking a full dose of hydrocortisone compared to controls (P < 0.001). There was no significant difference in the integrated CDC between patients on half-dose (P = 0.37) or no hydrocortisone treatment (P = 0.13), compared to control subjects. Peak postabsorption cortisol values were higher in patients receiving full-dose hydrocortisone treatment compared to controls (P < 0.001). There was no significant difference in plasma sodium concentration, blood pressure or corticosteroid-binding globulin between patients on any treatment schedule and controls. CONCLUSION Adult patients with pituitary disease and partial ACTH deficiency have a cortisol secretory pattern comparable to that of healthy controls. Conventional full-dose replacement with 10 mg twice daily of hydrocortisone produces hypercortisolaemia, whereas half-dose produces a CDC that is not statistically different from that of healthy controls. The results suggest that current conventional glucocorticoid replacement overtreats patients with partial ACTH deficiency under normal unstressed physiological conditions.
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10.
Hormone replacement therapy, calcium and vitamin D3 versus calcium and vitamin D3 alone decreases markers of cartilage and bone metabolism in rheumatoid arthritis: a randomized controlled trial [ISRCTN46523456].
Forsblad d'Elia, H, Christgau, S, Mattsson, LA, Saxne, T, Ohlsson, C, Nordborg, E, Carlsten, H
Arthritis research & therapy. 2004;(5):R457-68
Abstract
This study aimed to evaluate the effects of hormone replacement therapy (HRT), known to prevent osteoporosis and fractures, on markers of bone and cartilage metabolism. Furthermore, we assessed whether changes in these markers corresponded to alterations in bone mineral density and radiographic joint destructions in postmenopausal women with rheumatoid arthritis. Eighty-eight women were randomized to receive HRT, calcium, and vitamin D3, or calcium and vitamin D3 alone, for 2 years. Bone turnover was studied by analyzing serum levels of C-terminal telopeptide fragments of type I collagen (CTX-I), C-terminal telopeptide of type I collagen (ICTP), bone sialoprotein, and C-terminal propeptide of type I procollagen (PICP) and cartilage turnover by urinary levels of collagen type II C-telopeptide degradation fragments (CTX-II) and cartilage oligomeric matrix protein (COMP) in serum. Treatment with HRT resulted in decrease in CTX-I (P < 0.001), ICTP (P < 0.001), PICP (P < 0.05), COMP (P < 0.01), and CTX-II (P < 0.05) at 2 years. Reductions in CTX-I, ICTP, and PICP were associated with improved bone mineral density. Of the markers tested, CTX-I reflected bone turnover most sensitively; it was reduced by 53 +/- 6% in the patients receiving HRT. Baseline ICTP (P < 0.001), CTX-II (P < 0.01), and COMP (P < 0.05) correlated with the Larsen score. We suggest that biochemical markers of bone and cartilage turnover may provide a useful tool for assessing novel treatment modalities in arthritis, concerning both joint protection and prevention of osteoporosis.