ebook img

Neuroendocrine and behavioral effects of high-dose anabolic PDF

15 Pages·2003·0.08 MB·English
Save to my drive
Quick download

Preview Neuroendocrine and behavioral effects of high-dose anabolic

Psychoneuroendocrinology28 (2003)317–331 www.elsevier.com/locate/psyneuen Neuroendocrine and behavioral effects of high-dose anabolic steroid administration in male normal volunteers R.C. Daly ∗, T.-P. Su, P.J. Schmidt, M. Pagliaro, D. Pickar, D.R. Rubinow Behavioural EndocrinologyBranch, NationalInstitute ofMentalHealth, Building10,Room 3N238, 10Center DriveMSC1277, 20892-1277Bethesda, MD,USA Received22October 2001;received inrevisedform21 February2002;accepted 8 March2002 Abstract Objective: Despite widespread abuse of anabolic-androgenic steroids (AAS), the endocrine effects of supraphysiologic doses of these compounds remain unclear. We administered the AAS methyltestosterone (MT) to 20 normal volunteers in an in-patient setting, examined its effectsonlevelsofpituitary-gonadal,-thyroid,and-adrenalhormones,andexaminedpotential relationships between endocrine changes and MT-induced psychological symptoms. Method: Subjects received MT (three days of 40 mg/day, then three days of 240 mg/day) or placebo in a fixed sequence with neither subjects nor raters aware of order. Sampleswere obtained at theendsofthebaseline,high-doseMTandwithdrawalphases.Potentialrelationshipsbetween hormonal changes and visual analog scale measured mood changes were examined. Results: Significantdecreasesinplasmalevelsofgonadotropins,gonadalsteroids,sexhormonebinding globulin,freeT3andT4,andthyroidbindingglobulin(Bonferronit,p(cid:1)0.01foreach)were seenduringhigh-doseMT;freethyroxineandTSHincreasedduringhigh-doseMT,withTSH increases reaching significance during withdrawal. No significant changes in pituitary-adrenal hormones were observed. Changes in free thyroxine significantly correlated with changes in aggressiveness (anger, violent feelings, irritability) (r(cid:2)0.5,p(cid:2)0.02) and changes in total testosteronecorrelatedsignificantlywithchangesincognitiveclustersymptoms(forgetfulness, distractibility) (r(cid:2)0.52,p(cid:2)0.02). Hormonal changesdid not correlatewith plasma MT lev- els.Conclusions:Acutehigh-doseMTadministrationacutelysuppressesthereproductiveaxis and significantly impacts thyroid axis balance without a consistent effect on pituitary-adrenal ∗ Corresponding author.Tel.:+1-301-594-7377; fax:+1-301-402-2588. E-mailaddress: [email protected] (R.C. Daly). 0306-4530/03/$-seefrontmatterPublishedbyElsevierScienceLtd. doi:10.1016/S0306-4530(02)00025-2 318 R.C.Dalyetal./Psychoneuroendocrinology28(2003)317–331 hormones.MoodandbehavioraleffectsobservedduringAASusemayinpartreflectsecondary hormonal changes. Published by Elsevier Science Ltd. Keywords:Methyltestosterone;Anabolicsteroids;Aggression;Thyroid; Mood 1. Introduction Anabolic-androgenicsteroid(AAS)abusecanbeaccompaniedbyarangeofmood and behavioral disturbances, including irritability and aggression (Bahrke et al., 1990) and hypomania (Pope et al., 2000) and may represent a significant unrecog- nized public health problem (Pope et al., 2000). Despite an extensive literature on the psychotoxic effects of AAS, the mechanisms underlying these effects remain unknown.Methodologiclimitationsofpreviousstudiesexamininghormonalchanges during AAS use may have restricted their interpretation and generalization. These limitationsincludethecommonemploymentofoutpatientstudysettings(withresult- antpotentialconfoundingbypoorcompliance,exercise,orco-morbidsubstanceuse), administration of comparatively low doses of AAS, subject choice (e.g. seriously medically ill subjects), and lack of placebo controls. The widespread abuse of AAS (Yesalis et al., 1993) plus their recent emergence as a potential therapy in such conditions as HIV-related hypogonadism (Rabkin et al., 2000) dictate that we better understand the physiologic consequences of supraphysiologic doses of AAS. Such understanding would also potentially contribute to our knowledge of the biological mechanisms underlying behavioral disturbances accompanying AAS abuse. While the endocrine effects of androgens are well described, the hormonal effects of the massive doses of anabolic steroids taken by abusers are not clearly defined, and the needforfurtherinvestigationsemployingmoresophisticatedbatteriesofneuroendocrine measures has recently been emphasized (Pope et al., 2000). AAS use impacts upon severalhormonalsystems,mostnotablythehypothalamic-pituitary-adrenal(HPA),hypo- thalamic-pituitary-thyroid (HPT) and hypothalamic-pituitary-gonadal (HPG) axes (Clericoetal.,1981;Ale´netal.,1985,1987;DeyssigandWeissel,1993).Perturbations in these hormonal axes in association with affective and behavioral changes in other psychiatric conditions are well documented and presumed to be pathophysiologically relevant. Thus, changes in endocrine function secondary to AAS administration could potentially contribute to AAS-induced psychiatric changes. For example, some authors havesuggestedthatAAS-inducedadversebehavioralresponsesmayarisepartlythrough theireffectsonglucocorticoidreceptors(BonsallandMichael,1989;AhimaandHarlan, 1992) or estrogen levels (Bahrke et al., 1996). In an effort to more clearly define the hormonal changes that occur during high- dose AAS use and to explore possible mechanisms underlying the accompanying adverse behavioral changes, we carried out a comprehensive battery of neuroendoc- rine hormone measures during MT administration in our previously described (Su et al., 1993) study group. We studied hormonal axes that are known to potentially R.C.Dalyetal./Psychoneuroendocrinology28(2003)317–331 319 influencemoodandbehaviorandthathavealsobeenpreviouslyreportedaschanging during AAS use. Two specific questions were posed in this study. First, what are the acute effects of supraphysiologic doses of MT on circulating levels of HPA, HPT and HPG axes hormones when administeredunder carefully controlled conditions tohealthy volun- teers?Second,areMT-inducedhormonalchangesassociatedwiththebehavioraland mood symptoms observed? 2. Methods 2.1. Subjects Subjectselectionandprotocolareaspreviouslydescribed(Suetal.,1993)andare summarized as follows: 23 medication-free male volunteers aged 18–42 underwent extensive medical screening, including urine testing for illicit drugs; three were excluded due to medical problems or a positive drug screen. The remaining 20 sub- jects had no significant current or past history of psychiatric disorder or AAS use andwerefreeofanycurrentorrecent(pasttwoyears)historyofalcoholorsubstance abuse, confirmed with a standardized psychiatric interview, the Schedule for Affect- ive Disorders and Schizophrenia—Lifetime (Spitzer and Endicott, 1979), adminis- tered by a psychiatrist (TPS). After complete description of the study, written infor- med consent was obtained. The protocol was approved by the NIMH Institutional Review Board. Subjects were paid for their participation according to the schedule of payment issued by the National Institutes of Health Normal Volunteer Office. Followingatwo-dayacclimatizationperiodonanNIMHinpatientunit,allsubjects received MT or placebo, administered as three capsules t.i.d. These were adminis- tered in a fixed sequence, with neither subjects nor raters aware of the order of the administration of active drug and placebo. The following sequential schedule was used for each subject: three days of placebo (‘baseline’ phase), three days of MT 40 mg/day (‘low dose’ phase), three days of MT 240 mg/day (‘high-dose’ phase), and three days of placebo (‘withdrawal’ phase). Subjects were informed that the purposeofthestudywas tounderstandpossible behavioralactionsofAASandwere toldtheywouldbeaskedquestionregardingtheirmoodandthinkingonadailybasis. 2.2. Outcome measures 2.2.1. Plasma hormones Blood samples were collected at 8:00 a.m. on the final day of the baseline, high- dose,andwithdrawalconditions.(Bloodsampleswerenotuniformlyobtainedduring the low dose condition and are, therefore, not considered further.) Blood was drawn viavenipunctureintopre-chilledheparinorEDTAcontainingtubesoniceandcentri- fuged at 3000 rpm for 15 min. Samples were then promptly frozen at (cid:3)70 °C; the specimens were stored for a maximum of one year and the assays performed in one batch as soon as the study was completed. 320 R.C.Dalyetal./Psychoneuroendocrinology28(2003)317–331 2.2.2. Urinary cortisol Twoconsecutive24hurinesampleswerecollectedforurinaryfreecortisol(UFC) on the final two days of the baseline, high-dose, and withdrawal conditions. Asdescribedpreviously(Suetal.,1993)visualanaloguescale(VAS)ratingswere completed daily at 10:00 a.m., 6:00 p.m., and 10:00 p.m. for a range of subjective mood and behavioral measures. The reliability and validity of such analogue scales in rating subjective feelings has been established (Canat et al., 1992). The highest of the three ratings recorded each day was selected and then averaged for the three days of that particular drug condition, i.e. baseline, high-dose and withdrawal con- ditions. Mood and behavioral ratings were measured during all four phases of the study (baseline, low dose, high-dose and withdrawal). As reported in our previous study(Suetal.,1993),behavioralratingsduringthehigh-doseandwithdrawalphases werecomparedwiththe baselinephaseusingposthoc pairedt-testswhere permitted byresultsofanalysisofvariancewithrepeatedmeasures(ANOVA-R).Sevensymp- toms showed substantial change from the baseline to the high-dose phase (p(cid:4)0.1) (Table 1), while sexual arousal was the only symptom that significantly increased during withdrawal. These symptoms fellwithin our three previously observed (Su et al., 1993)behavioral symptomclusters:‘activation’ symptomcluster(energy, sexual arousal,diminishedsleep),‘aggressiveness’symptomcluster(anger,violentfeelings, irritability),and‘cognitive’symptomcluster(distractibility).Clusterscoreswerecal- culated by averaging the means from each contributory symptom. Cluster score changes, and not individual symptom score changes, were correlated with hormonal changes in order to decrease the number of comparisons made. To diminish the likelihood that a significant correlation would represent the effect of a single symp- tom, the symptom of memory was also included (p (cid:2) 0.13) to constitute the cogni- tive cluster. 2.3. Assays Assays were performed by Smith Kline Beecham Clinical Laboratories (testosterone, sex hormone binding globulin (SHBG), and UFC), Hazelton Labora- tories (adrenocorticotropic hormone (ACTH), cortisol, β-endorphin, dehydroepiand- rosterone (DHEA), dihydrotestosterone (DHT), and estradiol), and NIH Clinical CenterLaboratories(thyroxine(T4),freethyroxine(FT4),thyroxinebindingglobulin (TBG), thyroidstimulating hormone(TSH),albumin,luteinizing hormone(LH), and follicle stimulating hormone (FSH)). Free testosterone levels were calculated by a formula using testosterone, SHBG, and albumin (Sodergard et al., 1982). Free MT levels were kindly measured by Dr Christine Ayotte employing gas chromatography/mass spectroscopy (Ayotte, 1994). (For description of assay methods and characteristics, see Table 2.) 2.4. Statistical analysis Data were examined in the following ways: hormone levels were examined by ANOVA-R,withtreatmentconditionasthewithinsubjectsvariable,forthebaseline, R.C.Dalyetal./Psychoneuroendocrinology28(2003)317–331 321 1 0.03(cid:2)0.13(cid:2)0.010.001(cid:2)0.04(cid:2)0.00(cid:2)0.080.01(cid:2)0.07(cid:2)0.06(cid:2)0.04 (cid:2) (cid:2) (cid:2) pp ppp ppp 3,p56,69,2,p24,09,83,8,p93,00,25, bp (cid:2)(cid:2)(cid:2)(cid:2)(cid:2)(cid:2)(cid:2)(cid:2)(cid:2)(cid:2)(cid:2) t, ttttttttttt s e s a ph ng se ati andhigh-do HighdoserMean(SD) 9.3(8.8)7.2(9.8)11.4(12.4)31.5(16.9)42.0(28.5)35.3(31.1)17.2(16.8)18.5(12.3)7.4(11.6)27.1(20.3)20.9(19.8) e n eli s a b n e e w et b 20) ng (cid:2)scores(n BaselineratiMean(SD) 4.6(4.7)3.8(4.6)5.4(6.9)24.8(20.7)37.5(30.8)27.3(29.8)9.5(11.4)14.6(9.9)5.4(8.9)23.9(18.4)14.6(12.5) er st u cl m o pt m s. dsy sters ating n u r a cl e m m al mpto mpto er uesc Table1EffectofMTonbehavioralsy aBehavioralsymptomsandsy CognitivesymptomclusterForgetfulnessDistractibilityActivationsymptomclusterEnergySexualarousalDisturbedsleepAggressivenesssymptomclustAngerViolentfeelingsIrritability aMeasuredbyvisualanalog(cid:2)bPairedt-test,df19. 322 R.C.Dalyetal./Psychoneuroendocrinology28(2003)317–331 Table 2 Assaycharacteristics Assay CV Sensitivity limit Normal range Intraassay (%) Inter assay(%) ACTH(Nicholson etal., 9 19 5–10pg/ml 5–80pg/ml 1984) Albumina (Rodkey, 3 3 (cid:1)0.1g/l 3.7–4.7 g/l 1965) β-Endorphin(Healyet 9 17 25–50pg/ml 52–64pg/ml al.,1983) Cortisol(Abrahametal., 2 7 0.7ug/dl 8–18ug/dl 1972b) Cortisol, urinaryfreeb 3 6 5 meq/l 9–95ug/24 h (Ruderetal.,1972) DHEA(Busterand 11 12 12.5–25ng/dl 160–1200ng/dl Abraham,1972) DHT(Abraham,1973) 6 13 10ng/dl 30–90ng/dl Estradiol(Abrahamet 6 12 5–12pg/ml (cid:1)10–58pg/ml al.,1972a) FSHc 2 5 1.0mIU/ml 1–8mIU/ml LHc 3 5 2.5mIU/ml 2–12mIU/ml SHBG(Khanetal., 4 8 6 nmol/l 8–49nmol/l 1982) T3d 3 8 15ng/dl 88–162 ng/dl T4e 3 4 1.05 ug/dl 5–10ug/dl FT4f 5 9 0.08 ng/dl 1.0–1.9 ng/dl TBGg 5 6 1.0ug/ml 12–28ug/ml Testosterone,freeh 1 pg/ml 80–280 pg/ml Testosterone,total 5 10 20ng/dl 225–900 ng/dl (Abraham,1973) TSHi 3 7 0.03 uIU/ml 0.4–4.6 uIU/ml a Spectrophotometricdetermination. bHPLC. c Microparticleenzymeimmunoassay. dQuanticoat, KallestadDiagnostics,Chaska, MN. e Fluorescent polarizationimmunoassay(AXSYM,AbbottLaboratories, AbbottPark,IL). f GammaCoat, INCSTAR,Stillwater,MN. gIRMA, (Immophase,CorningMedical, Medford,MA). hCalculated—see Sodergardetal.,1982. iIRMA (MAIAClone, CIBACorningDiagnostics, E.Walpole, MA). high-dose and withdrawal phases. Where justified by the ANOVA, paired compari- sons were performed with post hoc Bonferroni t-tests. Spearman rank correlation coefficients were calculated both between behavioral cluster score changes and hor- monalmeasuresshowingsignificantchanges(betweenbaselineandhigh-dosephases on paired t-test (Bonferroni corrected p (cid:4) 0.05), and also between MT levels and hormonal changes. Additionally, subjects were divided into groups (n (cid:2) 7) showing R.C.Dalyetal./Psychoneuroendocrinology28(2003)317–331 323 the greatest and least change from baseline to high-dose condition in the activation, aggressiveness and cognitive symptom clusters. Hormone changes from baseline to high-dose condition were then compared between high symptom and low symptom groups using Student’s t-tests. The α-level of significance was p(cid:4)0.05 for analyses unless otherwise specified. Two-tailed t-tests were used. Data are presented as mean ± standard deviation (SD). 3. Results 3.1. Neuroendocrine effects 3.1.1. HPG axis (Table 3) Significant suppression of plasma levels of reproductive axis hormones was seen duringbothhigh-doseMTandwithdrawalconditionscomparedwithbaseline.Levels of gonadotropins also fell significantly during the high-dose condition, but returned to baseline values during the withdrawal condition. 3.1.2. HPT axis (Table 3) SignificantdecreasesinthelevelsofT3,T4andTBGwereseenduringbothhigh- dose and withdrawal conditions compared with baseline, while significant increases were seen in FT4 and TSH during the high-dose condition compared with baseline, Table 3 EffectsofMTon gonadaland thyroidaxishormones Hormones B(Mean±SD) HD (Mean±SD) W(Mean±SD) F p df Gonadalaxis Totaltestosterone 748.8(246.0) 290.4 (251.7)∗∗ 398.5(181.4)∗∗ 50.4 0.001 2,38 (ng/dl) Freetestosterone 203.6(57.3) 98.0 (87.8)∗∗ 132.2(52.7)∗∗ 23.8 0.001 2,38 (pg/ml) DHT(ng/dl) 139.2 (72.6) 54.5 (33.0)∗∗ 71.5(35.0)∗∗ 24.6 0.001 2,38 Estradiol(pg/ml) 41.8 (15.1) 25.8 (14.4)∗∗ 30.3(16.3)∗∗ 10.5 0.001 2,38 SHBG(nmol/l) 30.6 (9.6) 17.2 (6.4)∗∗ 16.8(6.8)∗∗ 53.7 0.001 2,38 FSH(mIU/ml) 8.8(1.1) 7.3(0.7)∗∗ 8.7(2.0) 9.7 0.001 2,38 LH(mIU/ml) 8.4(1.9) 5.4(1.6)∗∗ 9.2(2.5) 27.6 0.001 2,38 Thyroidaxis Triiodothyroxine 131.6 (17.9) 96.0 (9.6)∗∗ 107.4(11.3)∗∗ 83.6 0.001 2,38 (ng/dl) T4(ug/dl) 6.5(0.8) 5.8(1.0)∗∗ 6.0(1.0)∗ 7.6 0.005 2,38 TBG(ug/ml) 18.2 (2.9) 13.2 (3.5)∗∗ 14.2(3.2)∗∗ 48.0 0.001 2,38 TSH(uIU/ml) 1.9(1.0) 2.3(1.4)∗ 3.2(2.0)∗∗ 18.6 0.001 2,38 FT4(ng/dl) 1.2(0.2) 1.4(0.2)∗∗ 1.3(0.2)∗ 8.1 0.005 2,38 B,baseline;HD,high-dose;W,withdrawal;ANOVA-R,analysisofvariancewithrepeatedmeasures. AllBonferroni t-testp-valuesrepresent comparisonswith baseline(∗∗p(cid:1)0.01,∗p(cid:1)0.05). 324 R.C.Dalyetal./Psychoneuroendocrinology28(2003)317–331 with FT4 levels returning to baseline and TSH levels further increasing during the withdrawal condition. 3.1.3. HPA axis (Table 4) No significant changes were observed in HPA axis-related hormones during the high-dose condition,although therewasatrend forACTH levelsto risesignificantly during withdrawal. 3.2. Correlations Aggressiveness clusterscore changes correlatedsignificantly with changes in FT4 levels (r (cid:2) 0.50,p (cid:2) 0.03) (i.e., increased changes in aggression with increases in FT4 during high-dose) (Fig. 1). Cognitive cluster score changes correlated signifi- cantly with changes in total testosterone (r (cid:2) 0.52,p (cid:2) 0.02) and at a trend level with changes in freetestosterone levels(r (cid:2) 0.43,p (cid:2) 0.06)(i.e. increased cognitive symptoms with blunted decreases in testosterone and free testosterone) (Table 5). Activation cluster score changes did not correlate significantly with changes in any hormonal levels. NosignificantcorrelationsbetweenplasmaMTlevelsandhormonalchangeswere observed.Specifically,MTlevelsdidnotcorrelatesignificantlywithchangesinFSH (r (cid:2) (cid:3)0.09, p (cid:2) 0.72), TBG (r (cid:2) 0.04, p (cid:2) 0.87), plasma cortisol (r (cid:2) (cid:3) 0.25, p (cid:2) 0.31) or urinary cortisol (r (cid:2) 0.10, p (cid:2) 0.68), LH (r (cid:2) 0.06, p (cid:2) 0.80), ACTH (r (cid:2) 0.03, p (cid:2) 0.89), GH (r (cid:2) (cid:3)0.03, p (cid:2) 0.90), estradiol (r (cid:2) (cid:3) 0.37, p (cid:2) 0.12), DHEA (r (cid:2) (cid:3)0.09, p (cid:2) 0.71), total testosterone (r (cid:2) (cid:3)0.01, p (cid:2) 0.97) or free testosterone (r (cid:2) (cid:3)0.24, p (cid:2) 0.31), SHBG (r (cid:2) 0.36, p (cid:2) 0.14), FT4 (r (cid:2) 0.03, p (cid:2) 0.91), free T3 (r (cid:2) 0.11, p (cid:2) 0.64) or T4 (r (cid:2) 0.39, p (cid:2) 0.09). Table 4 EffectsofMTon pituitary-adrenalhormones Hormones B (Mean±SD) HD(Mean±SD) W(Mean±SD) ANOVA-R F p df Plasma (n(cid:2)20) ACTH(pg/ml) 41.9 (21.6) 37.7 (14.9) 59.2 (51.9)∗ 3.7 (cid:1)0.05 2,38 DHEA(ng/dl) 1167(525) 962(420) 999(434) 2.4 0.1 2,38 Cortisol(ug/dl) 18.6 (4.8) 17.1 (3.7) 18.8 (4.7) NS β-Endorphin(pg/ml) 30.1 (7.7) 31.8 (8.7) 32.9 (15.3) NS Urine (n(cid:2)19) 24h Cortisol 78.11(30.2) 74.3 (35.7) 83.9 (37.9) NS (ug/dl) NS,non-significantforallthreetreatmentconditions.Bonferronit-testp-valuesrepresentcomparisons with baseline(∗p(cid:1)0.1). R.C.Dalyetal./Psychoneuroendocrinology28(2003)317–331 325 Fig.1. CorrelationofchangesinaggressionsymptomclusterscoreswithchangesinplasmaFT4follow- ingMTadministration(r(cid:2)0.5,p(cid:2)0.02).Aggressionclusterincludesenergy,sexualarousal,anddimin- ishedsleep. Table 5 Spearmancorrelationcoefficientsofchangesinbehavioral symptomclusterscoreswith changesinhor- monallevels duringMT administration Aggressivenesscluster Activationcluster Cognitive cluster Totaltestosterone 0.25 0.15 0.52∗∗ Freetestosterone 0.08 0.19 0.43∗ DHT 0.11 0.10 0.33 Estradiol 0.23 0.23 0.31 FSH 0.41 (cid:3)0.20 –0.002 LH 0.25 –0.08 –0.15 T4 0.23 0.15 0.09 FT4 0.50∗∗ 0.15 –0.02 ∗p(cid:1)0.1,∗∗p(cid:1)0.05. 3.3. Split group comparisons For the activation cluster, a significant difference in FT4 changes between sub- groups was observed—the high symptom and low symptom subgroup changes were 0.19 ± 0.12ng/dl and 0.06 ± 0.05ng/dl respectively (t (cid:2) 2.56,p (cid:2) 0.02). No other significant differences in hormonal changes between high symptom and low symp- tom subgroups were observed (data not shown). 326 R.C.Dalyetal./Psychoneuroendocrinology28(2003)317–331 4. Discussion Several limitations of this study are notable. The duration of treatment with AAS was shorter and doses lower than those reported by some abusers (Porcerelli and Sandler,1998).Steroidabusingathletesmaycompriseadifferentbiologicalorbioso- cialgroupthanhealthyvolunteerswhohaveneverusedandrogens.Thestudydesign, byminimizing potentialconfoundssuch asexercise,co-morbid substanceabuse,and multiplesteroiduse,mayhavereducedtheimpactofimportantfactorsthatcontribute to AAS-induced psychological and hormonal changes. Correlational studies cannot establish causality, and multiple comparison analyses can lead to type 1 errors. This study is the first comprehensive examination of hormonal changes during and after high-dose AAS administration to drug naive normal volunteers in an in- patient setting. Inanearlierpublication(Suet al.,1993), wereportedthat behavioral effectsofMTwereseenevenunderthehighlycontrolledandtimelimitedconditions of this study; we also noted an association between increases in CSF 5HIAA levels andthedevelopmentofactivationsymptoms(Dalyetal.,2001).Inthecurrentreport, wedemonstrateacutesuppressiveeffectsofMTonthepituitary-gonadaland-thyroid axes. These effects were acute (occurring after only six days) and dramatic. Associ- ations were observed between some of the MT-induced changes in hormonal levels and the behavioral and mood symptoms observed. In the following sections, we examine the various endocrine effects of MT administration and attempt to interpret the associations seen between endocrine changes and psychological symptoms. 4.1. Pituitary-gonadal axis We observed decreases in SHBG and testosterone, consistent with the expected effects of androgen administration (Ale´n et al., 1987; Ruokonen et al., 1985; Small et al., 1984; Holma and Adlercreutz, 1976; Jones et al., 1977). We also observed suppression of gonadotropin levels, an effect reported in many (Clerico et al., 1981; Ale´n et al., 1985, 1987; Small et al., 1984), but not all (Hervey et al., 1976; Remes et al., 1977; Aakvaag and Stromme, 1974) studies. Additionally,subjectsshoweddecreasesinestradiollevelsfollowingMTadminis- tration, contrary to some earlier studies that reported increases in estradiol (Ale´n et al., 1985, 1987). The most likely explanation for this apparent difference is the use intheseearlierstudiesofandrogens(e.g.testosterone),whichmayundergoaromatiz- ation to estrogens; MT, a 17-alkylated androgen, does not undergo such metabolism (Dimick et al., 1961). Changes in testosterone levels have been suggested as influencing cognitive func- tioning through ‘activating effects’ (Hampson and Moffat, 1994; Van Goozen et al. (2000).Fewstudieshaveexaminedintra-subjectchangesincognitionaccompanying decreases in endogenous testosterone levels. Our findings of blunted decreases in testosterone being associated with increases in subjectively rated forgetfulness and distractibility (i.e. smaller decreases associated with increased symptoms) are para- doxical but consistent with prior literature suggesting a curvilinear relationship between one component of cognitive functioning—spatial performance—and circul-

Objective: Despite widespread abuse of anabolic-androgenic steroids (AAS), the Significant decreases in plasma levels of gonadotropins, gonadal steroids,
See more

The list of books you might like

Upgrade Premium
Most books are stored in the elastic cloud where traffic is expensive. For this reason, we have a limit on daily download.