Growth hormone and sex steroid administration in healthy aged women and men: a randomized controlled trial.

Division of Endocrinology and Metabolism, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
JAMA The Journal of the American Medical Association (Impact Factor: 30.39). 12/2002; 288(18):2282-92.
Source: PubMed

ABSTRACT Hormone administration to elderly individuals can increase lean body mass (LBM) and decrease fat, but interactive effects of growth hormone (GH) and sex steroids and their influence on strength and endurance are unknown.
To evaluate the effects of recombinant human GH and/or sex steroids on body composition, strength, endurance, and adverse outcomes in aged persons.
A 26-week randomized, double-blind, placebo-controlled parallel-group trial in healthy, ambulatory, community-dwelling US women (n = 57) and men (n = 74) aged 65 to 88 years recruited between June 1992 and July 1998.
Participants were randomized to receive GH (starting dose, 30 micro g/kg, reduced to 20 micro g/kg, subcutaneously 3 times/wk) + sex steroids (women: transdermal estradiol, 100 micro g/d, plus oral medroxyprogesterone acetate, 10 mg/d, during the last 10 days of each 28-day cycle [HRT]; men: testosterone enanthate, biweekly intramuscular injections of 100 mg) (n = 35); GH + placebo sex steroid (n = 30); sex steroid + placebo GH (n = 35); or placebo GH + placebo sex steroid (n = 31) in a 2 x 2 factorial design.
Lean body mass, fat mass, muscle strength, maximum oxygen uptake (VO(2)max) during treadmill test, and adverse effects.
In women, LBM increased by 0.4 kg with placebo, 1.2 kg with HRT (P =.09), 1.0 kg with GH (P =.001), and 2.1 kg with GH + HRT (P<.001). Fat mass decreased significantly in the GH and GH + HRT groups. In men, LBM increased by 0.1 kg with placebo, 1.4 kg with testosterone (P =.06), 3.1 kg with GH (P<.001), and 4.3 kg with GH + testosterone (P<.001). Fat mass decreased significantly with GH and GH + testosterone. Women's strength decreased in the placebo group and increased nonsignificantly with HRT (P =.09), GH (P =.29), and GH + HRT (P =.14). Men's strength also did not increase significantly except for a marginally significant increase of 13.5 kg with GH + testosterone (P =.05). Women's VO(2)max declined by 0.4 mL/min/kg in the placebo and HRT groups but increased with GH (P =.07) and GH + HRT (P =.06). Men's VO(2)max declined by 1.2 mL/min/kg with placebo and by 0.4 mL/min/kg with testosterone (P =.49) but increased with GH (P =.11) and with GH + testosterone (P<.001). Changes in strength (r = 0.355; P<.001) and in VO(2)max (r = 0.320; P =.002) were directly related to changes in LBM. Edema was significantly more common in women taking GH (39% vs 0%) and GH + HRT (38% vs 0%). Carpal tunnel symptoms were more common in men taking GH + testosterone (32% vs 0%) and arthralgias were more common in men taking GH (41% vs 0%). Diabetes or glucose intolerance occurred in 18 GH-treated men vs 7 not receiving GH (P =.006).
In this study, GH with or without sex steroids in healthy, aged women and men increased LBM and decreased fat mass. Sex steroid + GH increased muscle strength marginally and VO( 2)max in men, but women had no significant change in strength or cardiovascular endurance. Because adverse effects were frequent (importantly, diabetes and glucose intolerance), GH interventions in the elderly should be confined to controlled studies.

  • Source
    • "The drug used was testosterone enanthate (Sheffield- Moore et al. 2011; Page et al. 2005; Ferrando et al. 2003; Blackman et al. 2002), oxandrolone (Schroeder et al. 2005; Schroeder et al. 2004; Schroeder et al. 2003a), testosterone undecanoate (Emmelot-Vonk et al. 2008; Wittert et al. 2003), oxymetholone (Schroeder et al. 2003b), and Androgel (Kenny et al. 2010). The administration method used was oral (6 articles), injection (4 articles), and transdermal gel (1 article). "
    [Show abstract] [Hide abstract]
    ABSTRACT: The objective of this study was to evaluate the effects of steroid anabolic androgenic hormones use on lean mass gain in elderly men through a systematic review with a meta-analysis of randomized controlled studies. We systematically searched PubMed database until 4th October 2013. We included randomized placebo-controlled trials (RCT) that studied testosterone replacement therapy in men over 60 years of age, with total testosterone levels ≤550 ng/dl, observing gains in weight, lean mass tissue and fat mass as outcome. We excluded duplicated studies, studies which mixed men and women, and studies using weak androgens such as dehydroepiandrosterone or androstenedione. The initial search yielded 2681 articles, of which 26 were selected for full text analysis. In the end, 11 studies were included. However, 3 studies were not included in the meta-analysis. Meta-analysis showed that mean weight increased (lean mass), ranging from 1.65 (95 % CI, 1.61-1.69) to 6.20 (95 % CI, 5.22-7.18) kg, although it was heterogeneous (I (2) = 98 %). Effect estimate was 3.59 [2.38-4.81]. Androgen therapy decreased fat mass; effect estimate was -1.78 [-2.57, -0.99] that analysis had also a high level of heterogeneity (I (2) = 81 %). The results suggest that testosterone replacement therapy is able to increase muscle mass in elderly men and that is affected by the time that the treatment is carried out and the method of administration of the drug.
    Journal of the American Aging Association 02/2015; 37(1):9742. DOI:10.1007/s11357-014-9742-0 · 3.45 Impact Factor
  • Source
    • "Whether high GSK3 activity and/or inactivation of PI3K/Akt in peripheral blood cells increase CVD or cancer risk or poor outcome of cancer remains to be investigated. The study first elucidates how GSK3 activity is released and how cells become insensitive as well as die early, explaining why the body cells reduce use of the hormones with age (Denckla 1974; Blackman et al. 2002). Overstimulation-caused PI3K/Akt/GSK3 insensitivity and high GSK3 activity are the fundamentals to propose the alternative death hormones hypothesis. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Aging is linked to decrease of the body cell use of growth hormone (GH) and thyroxine, whereas the decrease is via “death hormones” inhibition? This study proposes different viewpoints. Since interleukin 17 receptor C (IL17RC) is highly expressed in tissues from age-related macular degeneration (AMD) patients, IL17RC signaling pathways are explored to evaluate Wnts/vascular endothelial growth factor (VEGF) expression and complement activity, which are pathological factors in AMD. IL17RC overexpression or VEGF treatment was performed in two cell lines for up to two-day. Real-time Quantitative PCR, confocal microscopy, immune-blot, MTT assay, etc. measured downstream effects. IL17RC overexpression increases Wnts and VEGF that forms complexes with Wnt-signaling components. VEGF or the Wnt-signaling components interacting with C3 suggests alternative complement pathway activation. Moreover, IL17RC-overexpressed cells or VEGF-treated cells for two-day, which is overstimulation, increase PI3K/Akt/GSK3 insensitivity and GSK3 activity, and decrease growth/survival. High GSK3 activity associates with many chronic diseases including type II Diabetes. This study shows high GSK3 activity can result from PI3K/Akt overstimulation. Type II Diabetes shows insulin resistance that the body cells decrease insulin use. Possessing little sensitive PI3K/Akt for receptor activation, cells after overstimulation, although live, hardly respond to PI3K/Akt activators including GH, thyroxine and insulin. These results suggest an alternative explanation of the body cells declining hormone use since various kinds of cell signaling-induced overstimulation events almost always linked to PI3K/Akt, increase with age. Playing pathological roles in senescence and diseases, overstimulation eventually generates health problems. Electronic supplementary material The online version of this article (doi:10.1186/2193-1801-3-356) contains supplementary material, which is available to authorized users.
    SpringerPlus 07/2014; 3:356. DOI:10.1186/2193-1801-3-356
  • Source
    • "When GHRT is added to lipid management therapy with HMG CoA reductase inhibitors (statins), it may promote a synergistic effect (Monson et al., 2007). The reduction in atherosclerosis with use of GHRT has been assessed by several studies evaluating carotid IMT (Pfeifer et al., 1999; Leonsson et al., 2002; Murata et al., 2003; Colao et al., 2008). In addition, GHRT has demonstrated improvement in pro-inflammatory and other cardiovascular risk markers, including C-reactive protein, apolipoprotein B, and homocysteine levels (Sesmilo et al., 2000, 2001). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Deficiency of growth hormone (GH) in adults results in a syndrome characterized by decreased muscle mass and exercise capacity, increased visceral fat, impaired quality of life, unfavorable alterations in lipid profile and markers of cardiovascular risk, decrease in bone mass and integrity, and increased mortality. When dosed appropriately, GH replacement therapy (GHRT) is well tolerated, with a low incidence of side effects, and improves most of the alterations observed in GH deficiency (GHD); beneficial effects on mortality, cardiovascular events, and fracture rates, however, remain to be conclusively demonstrated. The potential of GH to act as a mitogen has resulted in concern over the possibility of increased de novo tumors or recurrence of pre-existing malignancies in individuals treated with GH. Though studies of adults who received GHRT in childhood have produced conflicting reports in this regard, long-term surveillance of adult GHRT has not demonstrated increased cancer risk or mortality.
    Frontiers in Endocrinology 06/2013; 4:64. DOI:10.3389/fendo.2013.00064
Show more