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14/03/2019 7:32 am
Androgen use, hipogonadism, IGF-1, tamoxifen and tendons
As some of you might know, I have been having tendon issues since beggining AAS use that have affected my life seriously. Doctor's diagnose have been tendinitis, which never convinced me since my symptoms have always been a lot closer to tendinosis.
For those that might not know, tendinosis is a pathological condition characterised by an abnormaly high ratio of type III collagen (the weaker less abundant one in healthy connective tissue) to type I (the stronger and normally more abundant one). There's sometimes a bit of inflamation on the surrounding tissues. A tendon affected by tendinosis may not get beyond the initial stage of healing (in which is supposed to be a higher than normal ratio of the mentioned types of collagen) after normal damage induced by everyday activities or exercise and thus will lose it's strength and may eventually rupture.
An ecography made after a recent relapse showed no inflamation in the tendons in the painfull area, and all the doctor could say was that there may be a muscular rupture in that area, but he couldn't really tell, and it would be needed a magnetic ressonance exam to be sure. I am planning on doing this soon.
I am more and more convinced that my AAS use has something to do with this, and I'm trying to put together a theory based on the various arguments I have found untill now.
Number one would be the direct impact AAS have on type III collagen synthesis, collagen fibrils dysplasia, and the consequent reduction on tendon tensile strength, rupture strength and the normal biomechanics of the extremities (1,2,3,4,5,6,7,8). In a nutshell, the use of AAS in order to heal tendon injuries or to simulate collagen synthesis and therefore building stronger tendons seems to a load of crap. That famous post on AAS and collagen synthesis which throws a bunch of percentage on collagen synthesis with no references whatsoever is at best extremely doubtfull.
This alterations in the type of collagen III to type I ratio could in itself lead to the development of what is known as tendinosis (see link posted above).
Number two would be the reduction in growth factors shown to stimulate the synthesis of type I collagen on connective tissue, such as GH (9), IGF-1 (10,11,12,13,14) and TGF-beta1 (15,16), all of which could potencialy help reversing this altered ratio of collagen types due to heavy androgen use.
This reduction could happen by various motives.
One would be the androgen induced hipogonadism in the PCT period. Testosterone levels have been shown to directly correlate with GH and other growth factors release (17,18,19,20,21,22) so the low testosterone could have a negative impact on some of the growth factors that could potencially reverse the damage done by androgens.
Another motive would be the use of tamoxifen during and after a steroid cycle.
tamoxifen has been linked to reduction in IGF-1 levels that range from 19% to 47%(23,26,27,28,29,30,31,32,33,34), and in GH response to GHRH (24,25,27). Since GH seems to be not only regulating both IGF-1 but also TGF levels, tamoxifen may also be contributing to the aggravation of the tendon issues initiated by AAS.
In my case, all the episodes of tendinosis happened either when using tamoxifen during PCT teraphy (so while hipogonadal), after usage of androgens that stimulate collagen type III production, or during tamoxifen use with AAS in order to combat gynecomasty.
If anyone wants to discuss this and try to debunk my theory or my interpretation of the research, please go ahead.
There's txt file attached with most abstracts from studies referenced here
References:
1-Stimulation of collagen synthesis by the anabolic steroid Stanozolol.
Falanga V, Greenberg AS, Zhou L, Ochoa SM, Roberts AB, Falabella A, Yamaguchi Y.
University of Miami School of Medicine, Department of Dermatology, Miami Veterans Affairs Medical Center, Florida, USA.
2-Collagen synthesis in postmenopausal women during therapy with anabolic steroid or female sex hormones.
Hassager C, Jensen LT, Podenphant J, Riis BJ, Christiansen C.
Department of Clinical Chemistry, Glostrup Hospital, University of Copenhagen, Denmark.
3-The effects of anabolic steroids on rat tendon. An ultrastructural, biomechanical, and biochemical analysis.
Inhofe PD, Grana WA, Egle D, Min KW, Tomasek J.
Department of Orthopaedic Surgery, University of Oklahoma College of Medicine,
Oklahoma City, USA.
4-The effect of anabolic steroids on the biomechanical and histological properties of rat tendon.Miles JW, Grana WA, Egle D, Min KW, Chitwood J.
University of Oklahoma Health Sciences Center, Oklahoma City.
5-Anabolic steroid-induced tendon pathology: a review of the literature.Laseter JT, Russell JA.
Joe W. King Orthopedic Institute, Houston, TX 77030.
6-The effect of exercise and anabolic steroids on the mechanical properties and crimp morphology of the rat tendon.
Wood TO, Cooke PH, Goodship AE.
Comparative Orthopaedic Research Group, University of Bristol, England.
7-Tendon injuries induced by exercise and anabolic steroids in experimental mice.
Michna H.
8-Organisation of collagen fibrils in tendon: changes induced by an anabolic
steroid. I. Functional and ultrastructural studies.
Michna H.
9-Growth hormone influences the content and composition of collagen in the aorta from old rats.
Bruel A, Oxlund H.
Department of Connective Tissue Biology, Institute of Anatomy, University of
Aarhus, DK-8000, Aarhus, Denmark. [email protected]
10-Allampallam K, Chakraborty J, Robinson J. Effect of ascorbic acid and growth factors on collagen metabolism of flexor retinaculum cells from individuals with and without carpal tunnel syndrome. J Occup Environ Med 42(3):251-9, 2000.
11-Conti N A, Dahners L E. The effect of exogenous growth factors on the healing of ligaments. Trans Orthop Res Soc 18:60, 1993.
12-Letson A K, Dahners L E. The effect of combinations of growth factors on ligament healing. Clin Orthop 308;207-212, 1994.
13-Kurtz C A, Loebig T G, Anderson D D, DeMeo P J, Campbell P G. Insulin-like growth factor I accelerates functional recovery from Achilles tendon injury in a rat model. Am J Sports Med May-Jun;27(3):363-69, 1999.
14-Abrahamsson S O. Similar effects of recombinant human insulin-like growth factor I and II on cellular activities in flexor tendons of young rabbits: experimental studies in vitro. J Orthop Res Mar;15(2):256-62, 1997
15-Chang J, Thunder R, Most D, Longaker M T, Lineaweaver W C. Studies in flexor tendon wound healing: neutralizing antibody to TGF-beta1 increases postoperative range of motion. Plast Reconstr Surg Jan;105(1):148-55, 2000.
16-Chang J, Most D, Stelnicki E, Siebert J W, Longaker M T, Hui K, Lineweaver W C. Gene expression of transforming growth factor beta-1 in rabbit zone II flexor tendon wound healing: evidence for dual mechanisms of repair. Plast Reconstr Surg Sep;100(4):937-44, 1997.
17-Activation of the somatotropic axis by testosterone in adult men: evidence for a role of hypothalamic growth hormone-releasing hormone.Bondanelli M, Ambrosio MR, Margutti A, Franceschetti P, Zatelli MC, degli Uberti EC.Department of Biomedical Sciences and Advanced Therapies, Section of
Endocrinology, University of Ferrara, Ferrara, Italy.
18-Serum levels of insulin-like growth factor I and insulin-like growth factor-binding protein 1 correlate with serum free testosterone and sex hormone binding globulin levels in healthy young and middle-aged men.
Erfurth EM, Hagmar LE, Saaf M, Hall K.
Department of Internal Medicine, University of Lund, Sweden.
19-Low circulating levels of insulin-like growth factors and testosterone in chronically institutionalized elderly men.
Abbasi AA, Drinka PJ, Mattson DE, Rudman D.
Department of Medicine, Medical College of Wisconsin, Milwaukee.
20-Testosterone increases serum 1,25-dihydroxyvitamin D and insulin-like growth factor-I in hypogonadal men.
Hagenfeldt Y, Linde K, Sjoberg HE, Zumkeller W, Arver S.
Department of Clinical Chemistry I, Huddinge University Hospital, Sweden.
21-Chronic sex steroid exposure increases mean plasma growth hormone concentration and pulse amplitude in men with isolated hypogonadotropic hypogonadism.Liu L, Merriam GR, Sherins RJ.
22-Serum insulin-like growth factor-I and serum testosterone status of elderly men in an inpatient rehabilitation unit.
Kosasih JB, Abbasi AA, Rudman D.
Department of Physical Medicine & Rehabilitation, Medical College of Wisconsin, Milwaukee, USA.
23-Effect of low dose tamoxifen on the insulin-like growth factor system in healthy women.Bonanni B, Johansson H, Gandini S, Guerrieri-Gonzaga A, Torrisi R, Sandri MT, Cazzaniga M, Mora S, Robertson C, Lien EA, Decensi A.
24-Effect of tamoxifen on GH and IGF-1 serum level in stage I-II breast cancer patients.Mandala M, Moro C, Ferretti G, Calabro MG, Nole F, Rocca A, Munzone E, Castro A, Curigliano G.Division of Medical Oncology, European Institute of Oncology, Via Ripamonti 435, 20141-Milan, Italy. [email protected]
25-Inhibitory action on GHRH-induced GH secretion of chronic tamoxifen treatment in breast cancer.De Marinis L, Mancini A, Izzi D, Bianchi A, Giampietro A, Fusco A, Liberale I, Rossi S, Valle D.
Institute of Endocrinology, Catholic University School of Medicine, Rome, Italy.
[email protected]
26-Effect of tamoxifen on lipoprotein(a) and insulin-like growth factor-I (IGF-I) in healthy women.
Decensi A, Robertson C, Ballardini B, Paggi D, Guerrieri-Gonzaga A, Bonanni B, Manetti L, Johansson H, Barreca A, Bettega D, Costa A.
FIRC Chemoprevention Unit, European Institute of Oncology, Milan, Italy.
[email protected]
27-Effect of acute and chronic administration of tamoxifen on GH response to GHRH and on IGF-I serum levels in women with breast cancer.Corsello SM, Rota CA, Putignano P, Della Casa S, Barnabei A, Migneco MG, Vangeli V, Barini A, Mandala M, Barone C, Barbarino A.Institute of Endocrinology, Catholic University School of Medicine, Rome, Italy.
28-Enhancement of tamoxifen-induced suppression of insulin-like growth factor I gene expression and serum level by a somatostatin analogue.Huynh H, Pollak M.Department of Medicine, Lady Davis Research Institute, Jewish General Hospital,
Montreal,
29-In vivo inhibition of insulin-like growth factor I gene expression by tamoxifen.Huynh HT, Tetenes E, Wallace L, Pollak M.Department of Medicine, McGill University, Montreal, Quebec, Canada
30-Suppression of serum insulin-like growth factor-1 levels in breast cancer patients during adjuvant tamoxifen therapy.Friedl A, Jordan VC, Pollak M.Department of Pathology and Laboratory Medicine, University of Wisconsin, Madison
53792.
31-Influence of tamoxifen on plasma levels of insulin-like growth factor I and insulin-like growth factor binding protein I in breast cancer patients.Lonning PE, Hall K, Aakvaag A, Lien EA.
Department of Oncology, Haukeland University Hospital, Bergen, Norway.
32-tamoxifen reduces serum insulin-like growth factor I (IGF-I).
Pollak MN, Huynh HT, Lefebvre SP.McGill University, Montreal, Quebec, Canada.
33-ffect of tamoxifen on serum insulinlike growth factor I levels in stage I breast cancer patients.Pollak M, Costantino J, Polychronakos C, Blauer SA, Guyda H, Redmond C, Fisher B, Margolese R.
Department of Oncology, Jewish General Hospital, Montreal, Canada.
34-Effect of tamoxifen on plasma insulin-like growth factor I in patients with breast cancer.Colletti RB, Roberts JD, Devlin JT, Copeland KC.Department of Pediatrics, University of Vermont College of Medicine, Burlington 05405.
Topic starter
15/03/2019 6:50 am
Forgot the txt....
15/03/2019 7:41 am
i thought that its known fact some androgens increase collagens synthasis:
Recombinant human chorionic gonadotropin but not dihydroTestosterone alone stimulates osteoblastic collagen synthesis in older men with partial age-related androgen deficiency.
Meier C, Liu PY, Ly LP, de Winter-Modzelewski J, Jimenez M, Handelsman DJ, Seibel MJ.
Bone Research Program, ANZAC Research Institute, University of Sydney, Concord, NSW 2139, Australia.
Several randomized trials of androgen supplementation in older men have been undertaken. However, the relative contributions of testosterone (T) and estrogens on bone metabolism in aging men are controversial. Within the setting of two double-blind, placebo-controlled studies, we evaluated the effect of dihydrotestosterone (DHT) and recombinant human chorionic gonadotropin (rHCG) on bone turnover in healthy, community-dwelling older men with partial androgen deficiency (total T < or = 15 nmol/liter). In the first study, 35 men (age 68.3 +/- 6.8 yr; baseline T, 13.9 +/- 3.3 nmol/liter) were randomized to receive either daily transdermal DHT (n = 17) or placebo for 3 months. In the second study, 40 men (age 67.4 +/- 5.4 yr; baseline T, 11.4 +/- 2.2 nmol/liter) were randomized to receive either rhCG s.c. (n = 20), two injections weekly, or placebo for 3 months. The following parameters were measured before, monthly during, and 1 month after treatment: serum T, estradiol (E2), and LH; markers of bone formation, serum amino-terminal propeptide of type I procollagen (S-PINP) and osteocalcin; markers of bone resorption, serum carboxyterminal cross-linked telopeptide of type I collagen and urinary deoxypyridinoline. Compared with placebo, treatment with DHT significantly increased serum DHT and suppressed LH and T levels, whereas E2 concentrations and markers of bone turnover did not change. In contrast, rhCG therapy significantly increased both T and E2, with the increases in E2 being supraphysiological. At the same time, rhCG significantly increased S-PINP concentrations with peak levels after 1 month (Delta40%; P = 0.02 compared with placebo). In contrast, serum osteocalcin and carboxyterminal cross-linked telopeptide of type I collagen and urinary deoxypyridinoline levels did not change. The change in S-PINP levels correlated with the change in E2 levels (r = 0.59; P = 0.02) but not with a change in T. We conclude that in older men with partial age-related androgen deficiency, rhCG treatment stimulates osteoblastic collagen formation proportionally to increased E2 concentrations but does not alter markers of mature osteoblastic function or bone resorption. In contrast, treatment with a pure, nonaromatizable androgen (DHT) has no effect on bone turnover despite a 20-fold increase in serum levels. Bone resorption was not accelerated during unchanged (DHT) or increased (rhCG) E2 levels, suggesting that minimal E2 levels are needed to maintain stable resorption, although direct androgen receptor-mediated effects cannot be excluded. If androgen supplementation is required for aging men, aromatizable androgens with sufficient endogenous estrogenic activity may have the most beneficial effects on bone.
Topic starter
15/03/2019 8:28 am
i thought that its known fact some androgens increase collagens synthasis:Recombinant human chorionic gonadotropin but not dihydrotestosterone alone stimulates osteoblastic collagen synthesis in older men with partial age-related androgen deficiency.
Meier C, Liu PY, Ly LP, de Winter-Modzelewski J, Jimenez M, Handelsman DJ, Seibel MJ.
Bone Research Program, ANZAC Research Institute, University of Sydney, Concord, NSW 2139, Australia.
Several randomized trials of androgen supplementation in older men have been undertaken. However, the relative contributions of testosterone (T) and estrogens on bone metabolism in aging men are controversial. Within the setting of two double-blind, placebo-controlled studies, we evaluated the effect of dihydrotestosterone (DHT) and recombinant human chorionic gonadotropin (rhCG) on bone turnover in healthy, community-dwelling older men with partial androgen deficiency (total T < or = 15 nmol/liter). In the first study, 35 men (age 68.3 +/- 6.8 yr; baseline T, 13.9 +/- 3.3 nmol/liter) were randomized to receive either daily transdermal DHT (n = 17) or placebo for 3 months. In the second study, 40 men (age 67.4 +/- 5.4 yr; baseline T, 11.4 +/- 2.2 nmol/liter) were randomized to receive either rhCG s.c. (n = 20), two injections weekly, or placebo for 3 months. The following parameters were measured before, monthly during, and 1 month after treatment: serum T, estradiol (E2), and LH; markers of bone formation, serum amino-terminal propeptide of type I procollagen (S-PINP) and osteocalcin; markers of bone resorption, serum carboxyterminal cross-linked telopeptide of type I collagen and urinary deoxypyridinoline. Compared with placebo, treatment with DHT significantly increased serum DHT and suppressed LH and T levels, whereas E2 concentrations and markers of bone turnover did not change. In contrast, rhCG therapy significantly increased both T and E2, with the increases in E2 being supraphysiological. At the same time, rhCG significantly increased S-PINP concentrations with peak levels after 1 month (Delta40%; P = 0.02 compared with placebo). In contrast, serum osteocalcin and carboxyterminal cross-linked telopeptide of type I collagen and urinary deoxypyridinoline levels did not change. The change in S-PINP levels correlated with the change in E2 levels (r = 0.59; P = 0.02) but not with a change in T. We conclude that in older men with partial age-related androgen deficiency, rhCG treatment stimulates osteoblastic collagen formation proportionally to increased E2 concentrations but does not alter markers of mature osteoblastic function or bone resorption. In contrast, treatment with a pure, nonaromatizable androgen (DHT) has no effect on bone turnover despite a 20-fold increase in serum levels. Bone resorption was not accelerated during unchanged (DHT) or increased (rhCG) E2 levels, suggesting that minimal E2 levels are needed to maintain stable resorption, although direct androgen receptor-mediated effects cannot be excluded. If androgen supplementation is required for aging men, aromatizable androgens with sufficient endogenous estrogenic activity may have the most beneficial effects on bone.
Yes it is. Did you read the thread to the end?
15/03/2019 9:10 am
oh im sorry, i dont see anyone can disagree about AAS and tendones. but its intresting to read about relation between nolva and collagen synthasis.
15/03/2019 9:56 am
I guess you have seen this?
Part of the abstract:
quote:
The results suggest that high doses of AAS decrease the degradation and seem to increase the synthesis of type I collagen. Furthermore, high doses of AAS are suggested to enhance soft tissue collagen metabolism on the basis of increased type III collagen synthesis and elevated HP/LP ratio during the steroid administration period. Although the tissue-specific turnover of collagen of soft connective tissues remains unknown, the turnover of bone collagen seems not to change following the use of high doses of AAS, at least within the time interval of the present study.
I have an issue with the language here.
Do they meen it increases the type 3 collagen?
---------
Injury. 1998 Dec;29(10):769-73. Related Articles, Links
Ultrastructural analysis of ruptured tendon from anabolic steroid users.
Evans NA, Bowrey DJ, Newman GR.
Department of Orthopaedics, Cardiff Royal Infirmary, U.K.
Tendon rupture has been linked with anabolic steroid abuse on the basis of a small number of published case reports. Although experimental data from animal models suggest steroids alter the biomechanical properties of tendon, ultrastructural evidence to support this theory is lacking. Indeed, microscopic analysis of human tendon from steroid users has not previously been reported. In this study, specimens of ruptured human tendon from four patients were biopsied during surgical repair. Two of the subjects were anabolic steroid users, and two subjects were used as nonsteroid-user controls. Ruptured tendon from both groups was examined using electron microscopy. No differences in collagen fibril ultrastructure were seen. We conclude that anabolic steroids did not induce ultrastructural collagen changes that might predispose to tendon rupture in humans.
PMID: 10341901 [PubMed - indexed for MEDLINE]
Just two guys in each group, so I guess it doesn't say much
Topic starter
15/03/2019 10:34 am
oh im sorry, i dont see anyone can disagree about AAS and tendones.
I'm not sure you are understanding this, but AAS stimulated colagen is supposed to be mainly type III collagen, which should lead to weaker tendons.
Topic starter
15/03/2019 11:31 am
quote:
Originally posted by Qrios
[B]I guess you have seen this?
Part of the abstract:
I have an issue with the language here.
Do they meen it increases the type 3 collagen?
That's my interpretation of it.
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15/03/2019 12:05 pm
i would sure like to hear what nandi has to say about this
Topic starter
15/03/2019 12:36 pm
i would sure like to hear what nandi has to say about this
Me too...
Topic starter
15/03/2019 1:23 pm
Found an intesteresting study on tendon rupture:
In accordance with other studies, the proportion of type III collagen was increased in specimens of ruptured Achilles tendon.[8,10] Type III collagen is a major fibrillar collagen in compliant tissues such as skin and blood vessels,[2] and is found in normal tendons only in very small amounts.[11] Immunostaining of cultured nonwounded and wounded specimens of both normal and ruptured Achilles tendon with antibodies directed against type III collagen detected a significantly stronger staining reaction in the specimens of ruptured and tendinopathic tendon. This finding is in accordance with the study by Coombs et al.,[8] who used biochemical methods to determine the relative proportions of collagen types in normal and ruptured Achilles tendon.
From the present study, it appears that the physiologic proliferative response of tenocytes to trauma induces production of both types I and III collagen. However, the tenocytes from ruptured and tendinopathic tendons produce greater quantities of type III collagen. The presence of a reduced amount of type I collagen and an increased amount of type III collagen may result in the tendon being less resistant to stress, and thus at increased risk of rupture.[11] Indeed, in histochemical studies we have shown that there is no difference in staining ability for type III collagen between ruptured and tendinopathic tendon samples.[20] In this respect, therefore, tendinopathy can be considered a preliminary phase to tendon rupture. Only a small minority of patients with an Achilles tendon rupture report previous tendinopathic pain,[12,15,28] but practically all tendon samples from patients with an Achilles tendon rupture show severe degenerative changes.[12,13,20] At present, it is unclear what makes a degenerated tendon symptomatic, and therefore induce limitation of activities, or keeps it asymptomatic, thus allowing the degenerative process to continue and, eventually, result in a rupture after relatively minor stresses.[28]
The increased production of type III collagen (or a decreased production of type I collagen) may be an acquired feature of chronically injured tendons. It is also conceivable that tenocytes from some persons are primed to produce increased quantities of type III collagen or a decreased production of type I collagen.[17] Both instances probably coexist. It is possible that persons with an increased ability to produce type III collagen who, for occupational or athletic reasons, are exposed to repeated microtrauma to their tendons, produce more type III collagen than other persons, thus resulting in degeneration of their tendons, culminating in rupture. Also, it appears that the normal process of aging results in increased production of type III collagen,[10] and that other collagen types are produced in ruptured and tendinopathic Achilles tendons.[11,20]
15/03/2019 1:57 pm
Hi Mate,
Yup i agree here, I completely ruptured ther patella tendons from both !! knees about 6 months ago..i also blame this on my steroid history ..
But i am gonna start a GH cycle with some androgens in 3 weeks..
D.W.
Topic starter
15/03/2019 2:48 pm
Hi Mate,Yup i agree here, I completely ruptured ther patella tendons from both !! knees about 6 months ago..i also blame this on my steroid history ..
But i am gonna start a GH cycle with some androgens in 3 weeks..D.W.
Are you using the GH for connective tissue strengthening only? If so, what dosage are you using?
15/03/2019 3:49 pm
This might be of interest:
Acta Endocrinol (Copenh). 1991 Mar;124(3):278-82
Type I and III procollagen propeptides in growth hormone-deficient patients: effects of increasing doses of GH.
Topic starter
15/03/2019 4:33 pm
This might be of interest:Acta Endocrinol (Copenh). 1991 Mar;124(3):278-82Type I and III procollagen propeptides in growth hormone-deficient patients: effects of increasing doses of GH.
It is of interest. It is an argument against the use of GH against tendinosis though.