Oxandrolone Use Causes Dyslipidemia in Resistance-Training Practitioners

doi:10.21203/rs.3.rs-50105/v1

Download PDF

Research article

Oxandrolone Use Causes Dyslipidemia in Resistance-Training Practitioners

https://doi.org/10.21203/rs.3.rs-50105/v1

This work is licensed under a CC BY 4.0 License

Version 1

posted

You are reading this latest preprint version

Background: Several of young people and adults make use of anabolic-androgenic steroid (ASS), during resistance training. The purposes of this study were to compare blood and salivary parameters in male resistance training practitioners using oxandrolone with reference values, compare these with a control group in triplicate, and correlate salivary and blood parameters.

Methods: In this prospective analytical observational study, blood, saliva, and urine were collected from 22 individuals (oxandrolone group, OG, n = 11 and control group, CG, n = 11), and these samples were analyzed at three time points: before oxandrolone consumption, at cessation of oxandrolone use, and three months after cessation of oxandrolone use. Complete blood count, lipid profile, metabolites, and enzymes were analyzed from blood samples. Salivary flow, pH, triglycerides, urea, aspartate transaminase, alanine aminotransferase, phosphorus, and calcium were analyzed from saliva. Urinalysis was used for toxicological screening. Mann-Whitney U tests, chi-square analysis, Friedman's ANOVA, and Spearman’s correlation tests were performed, with significance p<0.05.

Results: We found a lower blood HDL level for the oxandrolone group (24 mg/dL) compared with the reference value (>40 mg/dL), as soon as its use ceased, and a return to normal HDL levels three months later (49 mg/dL, >40 mg/dL). We also found higher triglyceride level (177 mg/dL) in this group compared with the reference value (<175 mg/dL), three months after use.

Conclusions: Although there were distinct differences between the groups and timepoints, these did not show clinical relevance, as they were within typical values. There was no correlation between blood and salivary parameters, but it is clear that oxandrolone causes changes in the lipid profile of users.

Sports Medicine and Kinesiology

Orthopedics

Orthopedic Surgery

Oxandrolone

Blood

Saliva

Resistance Training

Anabolic Agents

Dyslipidemia

Approximately 75% of adults engage in physical activity in compliance with WHO guidelines [1]. One type of physical exercise chosen by young people and adults is resistance training, and its prevalence varies, for example, from 12 to 18% in gyms in the USA [2, 3]. Several of these individuals make use of anabolic-androgenic steroid (AAS), a synthetic testosterone analog with anabolizing activity [4–6]. These substances are used therapeutically in different dosages (for example 20 mg/day for 12 weeks) [7] for aesthetic purposes, ineffectively for weight maintenance [8], maintenance of skeletal muscles [9, 10], and sexual function [11]. In addition, AAS may be used for stabilization of body functionality, in fundamental movements like walking and squatting in individuals who need weekly hemodialysis [12] or who have hypogonadism [13].

Despite its therapeutic use, AAS are also indiscriminately used in supraphysiological doses (more than 600 mg/week) [14, 15] by many professional or recreational athletes aiming to increase sports performance [16–18], rapid gains in lean mass [13, 16–18, 19], and rapid loss of body fat [10], among other goals. Among several types of AAS, oxandrolone (OX) is one of the most used [23, 23–26]; high-frequency use (current and former users) made up 45.8% of one sample (n = 719; n = 329) in resistance-training practice (RTP) [27]. OX is used to increase performance [28–31], as well as to improve net protein balance and lean body mass in patients with serious burns [32, 33], Klinefelter Syndrome, metabolic diseases [34], oral pathologies, and HIV [33].

Several AAS side effects have been reported, such as hypercoagulability, venous thromboembolism, arterial thromboembolism, stroke, ligamentous injuries, disc herniation, arrhythmia, steatosis, renal failure, decreased testis volume, suppressed spermatogenesis, infertility, loss of libido, erectile dysfunction, and gynecomastia [35]. AAS have been shown to increase low-density lipoprotein (LDL), decrease high-density lipoprotein (HDL) [36–38], reduce luteinizing hormone (LH) [39, 40] and follicle-stimulating hormone (FSH) [37, 41, 42], decrease blood testosterone [43, 44], and increase alanine transaminase (ALT) and aspartate transaminase (AST) [45], as well as other liver enzymes [38]. In those using AAS, basal blood shows increased hemoglobin [18, 46], high hematocrit counts [47], and high inflammatory markers [48], including high white blood cell count [28], high neutrophil count [49], and high C-reactive protein (CRP) [50, 51]. These side-effects may result in costly treatment, and therefore a negative impact for public health [52].

While various biochemical parameters are evaluated in the blood, they are also measured from the saliva, a non-invasive method. Measurement of metabolites in the salivary fluid is considered a reliable method [53, 54]. Some substances can alter parameters, such as salivary flow reduction observed with use of hypoglycemic drugs [55], antidepressants, hypothyroidism, or contraceptives [56]. Other effects are also observed, such as increased pH from green tea consumption [57], decrease in salivary pH in crack cocaine users [58] and elevated alanine aminotransferase (ALT) [59] in patients with kidney disease [60]. Even though these studies evaluate different drugs and conditions, none has verified the salivary effect of OX. As far as we currently know, there are no studies that have aimed to verify and correlate blood and salivary effects in AAS users using a single AAS (confirmation by urine metabolite). Furthermore, many studies do not measure AAS used by urinalysis; doses are self-reported, but not compared with reference values [12, 30, 61–69].

Goals

The primary purpose of this study was to verify the effects of OX on blood and saliva compared with reference values, to compare parameters before, immediately after, and three months after volunteers had finished the OX cycle, and to correlate salivary and blood parameters.

Study Design

This is a prospective analytical observational study.

Ethical Procedures

The project was approved by the Ethics and Research Committee of the Pontifical Catholic University of Paraná under protocol number 2.556.109 and followed the STROBE Statement guideline. All participants signed an appropriate informed consent paperwork. The study was conducted with a high ethical standard, even when formal approval has been obtained.

Inclusion and exclusion criteria

Subjects were recruited through the dissemination of research on social networks, websites, WhatsApp, and the snowball technique. Information about volunteers from resistance-training programs was included in the study. Requirements were as follows: male, expressed intention of OX use, six months in AAS washout or never used AAS, and self-report of no drug treatment or history of cardiovascular, respiratory, hepatic, renal, musculoskeletal, or metabolic disorders [70, 71]. This study included individuals who participated in a resistance-training program in the six months before the beginning of the evaluations.

Those individuals who did not complete one or more stages of the study were excluded from the research. Other exclusion criteria were: any illness acquired during the training period and collections that interfered with the results; psychotropic drug use; consumption of more than 15 alcoholic beverages per week (≅ 30 g/day); fixed or mobile orthodontic braces, removable total or partial denture or fixed denture; and smoking. All of these factors can interfere with the production of saliva [72].

Sample selection

Thirty-seven male subjects were initially recruited by social networks via the snowball method [63, 73–76]. The researcher was approached by subjects (by telephone) who intended to use OX, while the 26 subjects in the CG contacted the researcher. Forty-four subjects attended a personal interview, during which it was explained that no one, at no time, would provide any AAS substance, and that information on the time of use or dosages was likewise not to be prescribed. Participants gave their consent to participate under these conditions. Sociodemographic data were provided in face-to-face interviews based on the criteria of the Brazilian Association of Research Companies (ABEP) from Brazil’s economic classification criterion [77], and information about age, weight, height, body mass index, total time (years) and frequency (days/week) of resistance-training practice, as well as training session time per week (minutes/day). In the end, 22 individuals remained in the study; reasons dropping out are shown in figure A.

Twenty-two subjects participated in all stages of the study: 11 OG and 11 CG (Table 1). Among OX users, all used an oral form, and dosages varied from 0.04 to 0.97 mg/kg (supplementary Table 2) (from 4 to 12 weeks, mean = 7.4 SD ± 2,2) (progressive or regressive), with no participant having a similar pattern of use. Nine (n = 9) individuals acquired AAS in drugstores, and two (n = 2) purchased the product via the Internet, ready to use and with registered trademarks.

Sample collection timepoints

Samples were collected and analyzed at three timepoints. For the OG, these timepoints were: T1, before drug use; T2, after OX use (mean of 7.4 SD 2.2 weeks); and T3, three months after use, as previously indicated [78]. Samples from the CG were collected at T1 in the same week as the OG, and T2 was collected eight weeks later, according to previous studies [79, 80]. The collection of CG T3 occurred three months after T2. Blood, saliva, and urine were all collected from 2 pm to 5 pm, from March to November of 2018.

Blood collection and analyses

Blood collection took place in the Biochemistry Laboratory at the School of Life Sciences located in the Pontifical Catholic University of Paraná. There was no indication of fasting. A nurse collected blood by radial artery puncture, and it was processed on the same day. Plasma biochemical analyses were performed on an AU480 Chemistry Analyzer (Beckman Coulter, Pasadena, CA), except for glucose measurement, which was performed using the Cobas Mira Plus device (Roche Diagnostic Systems, Basel, Switzerland). The reagents used were analysis-grade (Kovalent, São Gonçalo, Brazil). Hormones were measured on the UniCel DxI 800 Access Immunoassay System (Beckman Coulter, Pasadena, CA), and blood count on the Coulter LH 750 Hematology Analyzer (Beckman Coulter, Pasadena, CA). Blood counts included: erythrocytes, hemoglobin, hematocrit, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), red blood cell distribution width (RDW), leukocytes, basophils, eosinophils, band neutrophils, segmented neutrophils, lymphocytes, monocytes and platelets (Table 2). We also observed glucose, follicle-stimulating hormone (FSH), luteinizing hormone (LH), adrenocorticotropic hormone (ACHT), total testosterone, total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglycerides, estradiol, c-reactive protein (CRP), urea, amylase, albumin, calcium, creatinine, alkaline phosphatase (ALP), phosphorus and aspartate transaminase (AST) (Table 3).

Saliva collection and analyses

Saliva was collected by masticatory stimulation using a 1 cm sterile piece of rubber stimulator, with for 1 minute for oral self-cleaning and 5 minutes for chewing. All saliva produced was captured in an 80 ml universal collection flask and immediately assessed for pH with a digital pH-meter (Digimed, Analytical Instrumentation, model DM 20, São Paulo, Brazil). Sialometry was obtained by the gravimetry method. Samples were weighed with a precision analytical balance (Gehaka AG-200, São Paulo, Brazil). The calculated salivary flow is represented in mL per minute. For preparation and storage, samples were centrifuged at 2000 g for 5 minutes at room temperature to remove debris. The supernatant was separated and frozen until the time of analysis [81].

The equipment used for sialochemical analysis was the Cobas Mira Plus (Roche Diagnostic Systems, Basel, Switzerland). Bioclin reagents (Bioclin/Quibasa, Belo Horizonte, Brazil) were also used for analysis. The methodology followed was according to the manufacturer's recommendations. The sensitivity and method linearity are described in supplementary Table 1. Salivary variables evaluated were salivary flow, pH, triglycerides, urea, AST, alanine aminotransferase (ALT), phosphorus, and calcium (Table 4).

Urine collection and AAS Screening

Urine samples were self-collected and analyzed liquid chromatography system coupled to a quadrupole time-of-flight mass spectrometer (LC-QTOF) to quantify oxandrolone metabolites (OX) and testosterone for the three timepoints of the study (Table 5). We also to detect other AAS (Supplementary Text 1).

Statistical analysis

For statistical analysis, data normality was assessed using the Shapiro-Wilk test; where the data did not present a normal distribution, nonparametric statistics were used. Mann-Whitney U and chi-square tests were performed to compare anthropometric, demographic, blood, salivary, and urine variables between groups. On timepoints within groups, Friedman's ANOVA followed by the peer comparison test were made, with median compared to reference values. Spearman’s correlation test was used to calculate the relationship between blood, saliva, and urine testosterone. The p-value adopted was < 0.05. The software used was IBM SPSS 25.0 for Windows.

With relation to anthropometrics and sociodemographic characteristics, only schooling was different between groups (Table 1).

Table 1

Anthropometrics, training, and sociodemographic characteristics
Anthropometrics and Training characteristics	OG (n = 11) Mean (SD)		CG (n = 11) Mean (SD)
Age (year)	27,5(± 6,6)		23,7(± 2,8)
Weight (kg)	87,2(± 13,8)		76,0(± 10,9)
Height (m)	1,78(± 0,05)		1,76 (± 0,04)
BMI (kg/m²)	27,3(± 3,4)		24,4(± 2,6)
Total RT practice (year)	6,3(± 1,7)		5,2(± 3,4)
RT frequency (days/week)	4,7(± 1,0)		4,0(± 1,3)
Training session time (min)	67,7(± 31,4)		59,0(± 12,2)
Sociodemographic characteristics	n	%	n	%
Marital Status
Single	11	100	10	90,9
Married	0	0	1	9,1
Schooling
Complete higher education	4	36,4^A	0	0^B
Incomplete higher education	5	45,5^A	11	100^B
Complete secondary	2	18,2	0	0
Socioeconomic class
A	4	36,4	4	36,4
B1	2	18,2	5	45,5
B2	3	27,3	0	0
C1	2	18,2	2	18,2
Notes: Socioeconomic class is an average household income according to ABEP [77] A: 5.477,71 US$;B1: 2.446,97 US$; B2: 1.263,51 US$; C1: 698,68 US$; SD: Stand Deviation; RT = Resistance Training; BMI = Body Mass Index Uppercase letters: Chi-square p < 0,05. Values without letters mean no significant difference.

Concerning reference values, the OG presented a higher HDL level at T2, returning to normal levels at T3, and a triglyceride level that remained within a typical value range at T1 and T2, but went above this range at T3 (Table 3). For blood, salivary, and urinary testosterone variables, values found were in accordance with reference values (Tables 2, 4 and 5).

In comparisons between groups (OG X CG) at the three timepoints (T1, T2, and T3), significant increased OG blood values were found for: band neutrophils at T2, monocytes at T1, platelets at T1 and T2, LH at T1, and triglycerides at T2 and T3. In contrast, some variables showed a reduction in OG: total testosterone at T1 and T2, calcium at T3, and ALP at T1 and T2. For salivary metabolites, only the pH in OG was decreased, at T3. Moreover, OX urinary levels in OG increased at T2 but were then reduced at T3. Comparing HDL and triglycerides from the stratified oxandrolone group by instances of use per week, there were no significant differences (Supplementary Table 3).

When blood variables were compared between timepoints (T1 x T2; T2 x T3; T1 x T3) within each treatment group separately, OG showed: hemoglobin count reduced from T1 to T2; FSH increased from T1 to T3; HDL increased from T2 to T3; triglycerides increased from T1 and T2 to T3; estradiol increased from T1 and T2 to T3; calcium reduced from T1 and T2 to T3.

Table 2

Hemogram count (Group X Time)
		OG (n = 11)	CG (n = 11)
Hemogram variables
Variables	Times	Median	Median	Reference value [83]
Erythrocytes	T1	5,30^a	5,36^a	4,60–6,20 µL
	T2	5,07^a	5,20^b
	T3	5,12^a	5,47^ab
Hemoglobin	T1	15,90^a	15,70^ac	14,0–18,0 (g/dL)
	T2	15,60^b	15,80^b
	T3	15,60^ab	16,40^c
Hematocrit	T1	45,10^a	48,50^a	40,0–54,0 (mL/dL)
	T2	45,10^a	45,50^b
	T3	45,10^a	47,30^ab
MCV	T1	86,90^a	88,81^a	80,0–96,0 (fL)
	T2	86,80^a	87,82^ab
	T3	86,69^a	87,31^b
MCH	T1	29,51	29,77	26,0–34,0 (pg)
	T2	29,78	30,18
	T3	30,47	30,19
R.D.W.	T1	12,80	13,30	11,0–14,5 (%)
	T2	13,20	13,00
	T3	12,90	12,70
Leukocytes	T1	7.000,00^a	6.700,00^a	3.600–11.000 /µL
	T2	6.900,00^a	6.445,00^b
	T3	7.200,00^a	7.500,00^ac
Basophils	T1	0,00	0,00	0–100 /µL
	T2	44	46,00
	T3	0,00	0,00
Eosinophils	T1	146,00	138,00	50–400 /µL
	T2	124,00	164,00
	T3	216,00	97,00
Band neutrophils	T1	70,00^a	79,00^a	0–700 /µL
	T2	69,00^Aa	46,00^Bb
	T3	72,00^a	75,00^ac
Segmented neutrophils	T1	4.218,00^a	4.187,00^a	1.400–6.600 /µL
	T2	3.933,00^a	3.692,00^b
	T3	3.762,00^a	3.740,00^ab
Lymphocytes	T1	2.075,00	2.415,00	1.200–3.200 /µL
	T2	2.070,00	2.067,00
	T3	2.025,00	2.130,00
Monocytes	T1	490,00^Aa	232,00^Ba	300–900 /µL
	T2	504,00^a	516,00^b
	T3	574,00^a	497,00^b
Platelets	T1	268.000,00^Aa	212.000,00^Ba	150.000–450.000 /µL
	T2	269.000,00^Aa	207.000,00^Bb
	T3	238.000,00^a	211.111,00^ac

Table 3

Blood variables (Group X Time)
Blood variables
Glucose	T1	73,00	72,00	65–99 (mg/dL) [84]
	T2	86,00	83,00
	T3	85,00	81,00
FSH	T1	3,38^a	3,01^a	1,27–19,26 (mUI/mL) [85]
	T2	4,41^ab	4,91^b
	T3	4,36^b	4,78^b
LH	T1	4,26^A	3,00^B	1,24–8,62 (mUI/mL) [85]
	T2	3,35	4,70
	T3	5,22	4,35
ACHT	T1	22,00	16,00	< 46,0 (pg/mL) [86]
	T2	16,90	17,10
	T3	21,40	16,30
Total Testosterone	T1	358,45	414,23	175,00–781,00 (ng/dL) [85]
	T2	240,94^A	414,35^B
	T3	295,56^A	489,81^B
Total cholesterol	T1	183,00	154,00	< 190 (mg/dL) [87]
	T2	185,00	150,00
	T3	159,00	143,00
HDL	T1	47,00^ab	50,00^a	> 40 (mg/dL) [87]
	T2	24,00^a	45,00^a
	T3	49,00^b	47,00^a
LDL	T1	102,00^a	95,00^a	< 130 (mg/dL) [87]
	T2	111,00^a	91,00^ab
	T3	101,00^a	79,00^b
Triglycerides	T1	133,00^a	75,00^a	< 175 (mg/dL) [87]
	T2	91,00^Aa	69,00^Ba
	T3	177,00^Ab	90,00^Ba
Estradiol	T1	20,00^a	20,00^a	< 47 (pg/mL) [88]
	T2	23,00^a	21,00^ab
	T3	39,00^b	34,00^b
CRP	T1	0,67^a	0,32^a	< 5,00 (mg/L) [89]
	T2	0,56^a	0,53^b
	T3	0,70^a	0,51^ab
Urea	T1	42,00	39,00	17–43 (mg/dL) [88]
	T2	42,00	36,00
	T3	39,00	40,00
Amylase	T1	49,00	62,00	22–80 (U/L) [90]
	T2	52,00	67,00
	T3	53,00	57,00
Albumin	T1	4,90^a	4,90^ab	3,5–5,2 (g/dL) [85]
	T2	4,90^a	5,00^a
	T3	4,70^a	4,80^b
Calcium	T1	9,80^a	9,80^a	8,9–10,7 (mg/dL) [88]
	T2	9,60^a	9,50^b
	T3	9,30^Ab	9,70^Bab
Creatinine	T1	1,03	1,20	0,90–1,30 (mg/dL) [88]
	T2	1,12	1,06
	T3	1,03	1,01
ALP	T1	56,00^A	75,00^B	30–120 (U/L) [85]
	T2	49,00^A	69,00^B
	T3	57,00	68,00
Blood phosphorus	T1	3,60	3,80	2,7–4,5 (mg/dL) [91]
	T2	3,90	3,80
	T3	3,90	4,10
AST	T1	26,00	26,00	< 50 (U/L) [85]
	T2	27,00	25,00
	T3	26,00	23,00
ALT	T1	26,00	24,00	< 50 (U/L) [85]
	T2	34,00	24,00
	T3	28,00	24,00

Table 4

Salivary variables (Group X Time)
Saliva variables
Salivary flow	T1	0,82	1,11	> 0,7 ml/min [92]*
	T2	0,95	1,22
	T3	1,09	1,17
pH	T1	7,68	7,66	(6,1–8,0) [93]*
	T2	7,88	7,67
	T3	7,50^A	7,84^B
Triglycerides	T1	5,00	2,58	4,88 ± 0,21 (mg/dL) [94]*
	T2	2,58	2,58
	T3	2,58	2,58
Urea	T1	30,40	26,30	30,75 ± 9,63 (mg/dL) [95]*
	T2	23,40	20,90
	T3	25,90	22,40
AST	T1	14,00	12,00	20,8 ± 23,9 (U/L) [60]*
	T2	15,00	8,00
	T3	9,00	9,00
ALT	T1	3,00	2,00	8,67 ± 12,9 (U/L) [60]*
	T2	4,00	3,00
	T3	0,99	0,99
Phosphorus	T1	8,37	7,10	6,6 ± 5,1 (mg/dL) [94] *
	T2	10,96	5,67
	T3	5,70	6,73
Calcium	T1	0,48^a	0,53^ab	3,4 ± 2,7 (mg/dL) [96]*
	T2	0,35^a	0,23^a
	T3	0,51^a	0,38^b

Table 5

Urine variables (Group X Time)
Urine variables
Testosterone	T1	22,18	11,19	41.7 ± 34.8 (ng/mL) [97]*
	T2	12,89	13,55
	T3	19,15	12,83
OX	T1	0,00^a	0,00^a	(ng/mL)
	T2	31,35^Ab	0,00^Ba
	T3	0,00^ab	0,00^a
Uppercase letters represent differences in time between groups by Mann-Whitney U test.
Lowercase letters represent differences between the moments in both groups by Friedman's 2 × 2 comparison; Median values without letters mention the absence of any statistically significant difference
* The reference values for the saliva and urine variables were taken from studies, but there is no consensus on standardized methodologies

In the present study, there were no statistically significant correlations between blood, salivary, and urinary variables (Supplementary Table 4).

To our knowledge, this is the first study that evaluates blood and salivary parameters in OX users, with confirmation by urine metabolite quantification. Although there are differences between groups and timepoints, values of the dosed components were within the reference limits described in the literature. The main results show that there was no correlation among blood, saliva, and urine in OG. However, higher levels of inflammatory cells and lipids in OG are suggestive of inflammation and dyslipidemia.

Regarding education levels of the subjects, our results differ from previous studies [98], in which most subjects had completed high school, followed by higher education in progress. Our study showed that some of the subjects had completed higher education. However, the current research is in line with other studies, which revealed a higher prevalence of use among people with complete secondary and higher education, as well as those who are specialists in the profession, with aesthetic aspects as the primary motivation for use of AAS [99, 100]. Use of AAS does not depend on educational level; that is, having more or less education is not a determining factor for the use of AAS.

According to the WHO [101], low levels of HDL cholesterol, as well as high levels of triglycerides and LDL cholesterol, are important risk factors for cardiovascular disease. In fact, improving the lipid profile of individuals is the main preventive measure for cardiovascular diseases. [102]. In the present study, it was found that OX users had reduced levels of HDL cholesterol shortly after use of OX, returning to normal after three months. Despite HDL returning to normal, users had isolated hypertriglyceridemia three months after using OX. These data point to dyslipidemia in OX users.

Interestingly, in a previous study, OX was tested as a cholesterol-lowering drug. The authors proposed 7.5 mg/day for three months, followed by washout for two months, and showed that HDL decreased significantly in patients under these conditions. At the same time, they observed high cholesterol levels [103]. Another study focusing on subjects with metabolic syndrome used oral OX at doses of 10 mg/day for one week, and also found reductions in HDL levels, with marked increases in hepatic ketogenesis. This was due to increased influx of fatty acids into the liver. However, it is not possible to exclude the possibility that short-term administration of OX acts directly on the liver to stimulate the oxidation of fatty acids [104]. In a study aimed at treatment of Klinefelter syndrome with oral OX 0.06 mg/kg/day or placebo for two years, HDL was lowered [105]. In our study, the reduction in HDL was observed, but it was also observed that, immediately after cessation of OX use, HDL levels return to normal, despite differences between the research subjects. Meanwhile, triglyceride levels remained high, pointing to the action of OX on fat metabolism and negative impacts on the cardiovascular system.

Although anabolic steroids in high doses are used for short periods of time [106], many athletes abuse these anabolic steroids and self-administer doses up to 100- and even 1000-fold more than safe doses, producing circulating testosterone levels two to three orders of magnitude above the healthy male reference range, often for prolonged periods. The maximal anabolic dose of testosterone is not known, but almost certainly vastly exceeds 600 mg of testosterone a week [107]. Excess doses cause dyslipidemia secondary to drugs increasing total cholesterol, create no changes in triglycerides, and decrease HDL [108, 109]. In the present study, we were unable to determine the exact dose of OX used by the volunteers, but we suggest that they were supraphysiological doses, and that they caused a consistent effect of OX on HDL production.

OX has been used for therapeutic purposes in many different situations [78, 79, 110–112]. A study of HIV-infected men that was not controlled for antiretroviral intake treated with OX daily for 12 weeks and reduced HDL for all doses of OX studied [33]. In an animal model, OX elevated triglycerides, reduced HDL, decreased hepatic triglycerides, and elevated levels of non-esterified fatty acids produced by the liver, possibly leading to increased lipidic synthesis of hepatic triglycerides [113]. Additionally, OX may reduce blood triglycerides by further activation of the triglyceride lipase that results in hydrolysis of peripheral triglycerides. Once the intake of OX ceases, triglycerides increase [114]. For the purpose of comparison, we used in this study the reference values of the Brazilian population for triglycerides; the results indicate a significantly increased, almost borderline, risk for cardiovascular disease after ceasing OX use. According WHO classification, individuals who have triglyceride level higher than 180 mg/dl are risk groups for cardiovascular disease. In addition, the results found here for triglycerides were consistent with other studies; that is, increased lipolysis and liberation of free fatty acid with the use of OX [78, 79, 110–112]. However, three months after ending OX use, this variable was higher than the reference standards.

This contradictory result can perhaps be explained by the management of OX, including different doses, different monitoring times, the practice of resistance exercises, days of use, types of cycle, and other variables. Also, the short time of evaluation after use could be a variable. Washout of three or more months may take these parameters back to normal [78, 115]. Despite this, our research presents relevant methodological criteria that were used in the study: comparison with reference values and the detection of metabolite in urine, among others. Studies show that the AAS cycle (duration use) [116] can last from 10 to 12 weeks [4, 117–119], close to the timeframe of this study. It is important that we evaluated a single, isolated AAS. Other studies have not reported standardization in blood sample collection times [70, 120], in contrast to a previous study that reported collection between 10 and 12 a.m. [51].

Limitations of our study have to be considered. The results found in our study were different from the studies mentioned above, perhaps because they did not follow the subjects several months after ending the use of AAS. We did not make a standardized dose, or limit cycles, because OX is a controlled drug, and its prescription is provided only by physicians. Another limitation is that the subjects’ family history of atherosclerotic disease was unknown. Micronutrient and macronutrient intake, training intensity, and endurance also were not analyzed. The selection of subjects and randomness of groups would be necessary for subsequent studies.

This study showed, for the first time, reference values of saliva taken from previous research, for comparative purposes about what OX can change, as well as what implications this can have. Additionally, even though there is no consensus in the literature on these values, the use of salivary markers is a non-invasive method, cheaper than blood tests, and may facilitate future studies.

This study provides evidence that the use of oxandrolone promotes dyslipidemia when used in non-therapeutic doses.

AAS – Anabolic-androgenic steroid

OX – oxandrolone

RTP – resistance-training practice

LDL – low-density lipoprotein

HDL – high-density lipoprotein

LH – luteinizing hormone

FSH- follicle-stimulating hormone

ALT – alanine transaminase

AST – aspartate transaminase

CRP – C-reactive protein

ABEP - Brazilian Association of Research Companies

OG – oxandrolone group

CG – control group

MCV – mean corpuscular volume

MCH – mean corpuscular hemoglobin

RDW – red blood cell distribution width

ACHT – adrenocorticotropic hormone

Ethics approval and consent to participate:

The project was approved by the Ethics and Research Committee of the Pontifical Catholic University of Paraná under protocol number 2.556.109.

Consent for publication:

Not applicable

Availability of data and materials

All data generated or analyzed during this study are included in this published article.

Competing interests

The author declare that they have no competing interests

Funding

None

Author’s contributions

DLG performed most of the research and described their result appointments and as well drafting the manuscript. EP and TFO participated in the recruiting people as also reviewing the manuscript. TBDB, SEFO, LB, LCSB and JSJ was responsible for the clinical agenda, medicating contact with the participants. PM, FA, MHMC and RIW responsible by blood analysis. FT responsible for reviewing the manuscript. MMTB responsible saliva table. EARR, MFS and SACP supervising the clinical procedures. EC, YYG and SAI responsible by the statistical analysis. JAB did the oxandrolone reading sheets. ACBRJ as the group leader, gave the guidelines for the whole project execution. All authors have read and approved the manuscript.

Acknowledgements

The thank PUCPR which allowed us to conduct this work.

Rhodes RE, Janssen I, Bredin SSD, Warburton DER, Bauman A. Physical activity: Health impact, prevalence, correlates and interventions. Psychol Heal. 2017;32: 942–975. doi:10.1080/08870446.2017.1325486
Jampel JD, Murray SB, Griffiths S, Blashill AJ. Self-Perceived Weight and Anabolic Steroid Misuse among US Adolescent Boys. J Adolesc Heal. 2016;58: 397–402. doi:10.1016/j.jadohealth.2015.10.003
Ip EJ, Doroudgar S, Lau B, Barnett MJ. Anabolic steroid users’ misuse of non-traditional prescription drugs. Res Soc Adm Pharm. 2019;15: 949–952. doi:10.1016/j.sapharm.2018.07.003
Llewellyn’s W. Anabolics. 10th ed. Júpiter, FL: Molecular Nutrition; 2010.
Bahrke MS, Yesalis CE. Abuse of anabolic androgenic steroids and related substances in sport and exercise. Curr Opin Pharmacol. 2004;4: 614–620. doi:10.1016/j.coph.2004.05.006
Yesalis CE, Bahrke MS. Anabolic-Androgenic Steroids: Current Issues. Sport Med. 1995;19: 326–340. doi:10.2165/00007256-199519050-00003
Schroeder ET, Zheng L, Yarasheski KE, Qian D, Stewart Y, Flores C, et al. Treatment with oxandrolone and the durability of effects in older men. J Appl Physiol. 2004;96: 1055–1062. doi:10.1152/japplphysiol.00808.2003
Tran A, Suharlim C, Mattie H, Davison K, Agénor M, Austin SB. Dating app use and unhealthy weight control behaviors among a sample of U.S. adults: A cross-sectional study. J Eat Disord. 2019;7. doi:10.1186/s40337-019-0244-4
Neto WK, Gama EF, Rocha LY, Ramos CC, Taets W, Scapini KB, et al. Effects of testosterone on lean mass gain in elderly men: systematic review with meta-analysis of controlled and randomized studies. Age (Omaha). 2015;37. doi:10.1007/s11357-014-9742-0
Bhasin S, Woodhouse L, Storer TW. Proof of the effect of testosterone on skeletal muscle. J Endocrinol. 2001;170: 27–38. doi:10.1677/joe.0.1700027
Davis SR, Wahlin-Jacobsen S. Testosterone in women-the clinical significance. Lancet Diabetes Endocrinol. 2015;3: 980–992. doi:10.1016/S2213-8587(15)00284-3
Johansen KL, Painter PL, Sakkas GK, Gordon P, Doyle J, Shubert T. Effects of Resistance Exercise Training and Nandrolone Decanoate on Body Composition and Muscle Function among Patients Who Receive Hemodialysis: A Randomized, Controlled Trial. J Am Soc Nephrol. 2006;17: 2307–2314. doi:10.1681/asn.2006010034
Wu C, Kovac JR. Novel Uses for the Anabolic Androgenic Steroids Nandrolone and Oxandrolone in the Management of Male Health. Curr Urol Rep. 2016;17: 1–7. doi:10.1007/s11934-016-0629-8
Pope HG, Kouri EM, Hudson JI. Effects of supraphysiologic doses of testosterone on mood and aggression in normal men: A randomized controlled trial. Arch Gen Psychiatry. 2000;57: 133–140. doi:10.1001/archpsyc.57.2.133
Schmidt PJ, Berlin KL, Danaceau MA, Neeren A, Haq NA, Roca CA, et al. The effects of pharmacologically induced hypogonadism on mood in healthy men. Arch Gen Psychiatry. 2004;61: 997–1004. doi:10.1001/archpsyc.61.10.997
De M, Mendes Barbalho S, Pereira Barreiros F. The Use and Effect of Anabolic Androgenic Steroids in Sports. Artic Int J Sport Sci. 2015;2015: 171–179. doi:10.5923/j.sports.20150505.01
Barceloux DG, Palmer RB. Anabolic-Androgenic Steroids. Disease-a-Month. 2013;59: 226–248. doi:10.1016/j.disamonth.2013.03.010
Pope HG, Wood RI, Rogol A, Nyberg F, Bowers L, Bhasin S. Adverse health consequences of performance-enhancing drugs: An endocrine society scientific statement. Endocr Rev. 2014;35: 341–375. doi:10.1210/er.2013-1058
Cheung AS, Grossmann M. Physiological basis behind ergogenic effects of anabolic androgens. Mol Cell Endocrinol. 2018;464: 14–20. doi:10.1016/j.mce.2017.01.047
Hoffman JR, Ratamess NA. Medical issues associated with anabolic steroid use: are they exaggerated? J Sports Sci Med. 2006;5: 182–93. Available: http://www.ncbi.nlm.nih.gov/pubmed/24259990%0Ahttp://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC3827559
Hartgens F, Kuipers H. Effects of androgenic-anabolic steroids in athletes. Sport Med. 2004;34: 513–554. doi:10.2165/00007256-200434080-00003
Andrews MA, Magee CD, Combest TM, Allard RJ, Douglas KM. Physical Effects of Anabolic-androgenic Steroids in Healthy Exercising Adults: A Systematic Review and Meta-analysis. Curr Sports Med Rep. 2018;17: 232–241. doi:10.1249/JSR.0000000000000500
Guddat S, Fußhöller G, Beuck S, Thomas A, Geyer H, Rydevik A, et al. Synthesis, characterization, and detection of new oxandrolone metabolites as long-term markers in sports drug testing. Anal Bioanal Chem. 2013;405: 8285–8294. doi:10.1007/s00216-013-7218-1
Mavros Y, O’Neill E, Connerty M, Bean JF, Broe K, Kiel DP, et al. Oxandrolone augmentation of resistance training in older women: A randomized trial. Med Sci Sports Exerc. 2015;47: 2257–2267. doi:10.1249/MSS.0000000000000690
Kahn NN, Sinha AK, Spungen AM, Bauman WA. Effects of oxandrolone, an anabolic steroid, on hemostasis. Am J Hematol. 2006;81: 95–100. doi:10.1002/ajh.20532
Stanojcic M, Finnerty CC, Jeschke MG. Anabolic and anticatabolic agents in critical care. Curr Opin Crit Care. 2016;22: 325–331. doi:10.1097/MCC.0000000000000330
Pereira E, Moyses SJ, Ignácio SA, Mendes DK, Da Silva DS, Carneiro E, et al. Anabolic steroids among resistance training practitioners. PLoS One. 2019;14: 1–13. doi:10.1371/journal.pone.0223384
Hartgens F, Kuipers H. Effects of androgenic-anabolic steroids in athletes. Sport Med. 2004;34: 513–554. doi:10.2165/00007256-200434080-00003
Fink J, Schoenfeld BJ, Hackney AC, Matsumoto M, Maekawa T, Nakazato K, et al. Anabolic-androgenic steroids: procurement and administration practices of doping athletes. Phys Sportsmed. 2019;47: 10–14. doi:10.1080/00913847.2018.1526626
Westerman ME, Charchenko CM, Ziegelmann MJ, Bailey GC, Nippoldt TB, Trost L. Heavy Testosterone Use Among Bodybuilders: An Uncommon Cohort of Illicit Substance Users. Mayo Clin Proc. 2016;91: 175–182. doi:10.1016/j.mayocp.2015.10.027
Abrahin OSC, De Sousa EC. Esteroides anabolizantes androgênicos e seus efeitos colaterais: Uma revisão crítico-científica. Rev da Educ Fis. 2013;24: 669–679. doi:10.4025/reveducfis.v24.4.17580
Mavros Y, O’Neill E, Connerty M, Bean JF, Broe K, Kiel DP, et al. Oxandrolone augmentation of resistance training in older women: A randomized trial. Med Sci Sports Exerc. 2015;47: 2257–2267. doi:10.1249/MSS.0000000000000690
Grunfeld C, Kotler DP, Dobs A, Glesby M, Bhasin S. Oxandrolone in the treatment of HIV-associated weight loss in men: A randomized, double-blind, placebo-controlled study. J Acquir Immune Defic Syndr. 2006;41: 304–314. doi:10.1097/01.qai.0000197546.56131.40
Davis SM, Cox-Martin MG, Bardsley MZ, Kowal K, Zeitler PS, Ross JL. Effects of oxandrolone on cardiometabolic health in boys with klinefelter syndrome: A randomized controlled trial. J Clin Endocrinol Metab. 2017;102: 176–184. doi:10.1210/jc.2016-2904
Nieschlag E, Vorona E. Medical consequences of doping with anabolic androgenic steroids: effects on reproductive functions. Eur J Endocrinol. 2015;173: 47–58. doi:10.1530/EJE-15-0080
Andrews MA, Magee CD, Combest TM, Allard RJ, Douglas KM. Physical Effects of Anabolic-androgenic Steroids in Healthy Exercising Adults. Curr Sports Med Rep. 2018;17: 232–241. doi:10.1249/jsr.0000000000000500
Grevik N, Strahm E, Garle M, Lundmark J, Sthle L, Ekström L, et al. Long term perturbation of endocrine parameters and cholesterol metabolism after discontinued abuse of anabolic androgenic steroids. J Steroid Biochem Mol Biol. 2011;127: 295–300. doi:10.1016/j.jsbmb.2011.08.005
Carson P, Hong CJ, Otero-Vinas M, Arsenault EF, Falanga V. Liver enzymes and lipid levels in patients with lipodermatosclerosis and venous ulcers treated with a prototypic anabolic steroid (stanozolol): A prospective, randomized, double-blinded, placebo-controlled trial. Int J Low Extrem Wounds. 2015;14: 11–18. doi:10.1177/1534734614562276
Björkhem-Bergman L, Lehtihet M, Rane A, Ekström L. Vitamin D receptor rs2228570 polymorphism is associated with LH levels in men exposed to anabolic androgenic steroids. BMC Res Notes. 2018;11: 4–9. doi:10.1186/s13104-018-3173-4
Graham M, Davies B, Kicman A, Cowan D, Hullin D, Baker J. Recombinant Human Growth Hormone in Abstinent Androgenic-Anabolic Steroid Use: Psychological, Endocrine and Trophic Factor Effects. Curr Neurovasc Res. 2007;4: 9–18. doi:10.2174/156720207779940699
Rasmussen JJ, Selmer C, østergren PB, Pedersen KB, Schou M, Gustafsson F, et al. Former abusers of anabolic androgenic steroids exhibit decreased testosterone levels and hypogonadal symptoms years after cessation: A case-control study. PLoS One. 2016;11: 1–16. doi:10.1371/journal.pone.0161208
Venâncio DP, da Nóbrega ACL, Tufik S, de Mello MT. Avaliação descritiva sobre o uso de esteroides anabolizantes e seu efeito sobre as variáveis bioquímicas e neuroendócrinas em indivíduos que praticam exercício resistido. Rev Bras Med do Esporte. 2010;16: 191–195. doi:10.1590/s1517-86922010000300007
Gårevik N, Börjesson A, Choong E, Ekström L, Lehtihet M. Impact of single-dose nandrolone decanoate on gonadotropins, blood lipids and HMG CoA reductase in healthy men. Andrologia. 2016;48: 595–600. doi:10.1111/and.12488
Rasmussen JJ, Selmer C, østergren PB, Pedersen KB, Schou M, Gustafsson F, et al. Former abusers of anabolic androgenic steroids exhibit decreased testosterone levels and hypogonadal symptoms years after cessation: A case-control study. PLoS One. 2016;11: 1–16. doi:10.1371/journal.pone.0161208
Anabolic steroid abuse: Physiological and anaesthetic considerations. Anaesthesia. 2005;60: 685–692. doi:10.1111/j.1365-2044.2005.04218.x
Quaglio G, Fornasiero A, Mezzelani P, Moreschini S, Lugoboni F, Lechi A. Anabolic steroids: Dependence and complications of chronic use. Intern Emerg Med. 2009;4: 289–296. doi:10.1007/s11739-009-0260-5
Ööpik V, Timpmann S, Rips L, Olveti I, Kõiv K, Mooses M, et al. Anabolic Adaptations Occur in Conscripts During Basic Military Training Despite High Prevalence of Vitamin D Deficiency and Decrease in Iron Status. Mil Med. 2017;182: e1810–e1818. doi:10.7205/milmed-d-16-00113
Christou GA, Christou MA, Žiberna L, Christou KA. Indirect clinical markers for the detection of anabolic steroid abuse beyond the conventional doping control in athletes. Eur J Sport Sci. 2019;19: 1276–1286. doi:10.1080/17461391.2019.1587522
NT S. A review of the chemistry, biological action, and clinical applications of anabolic-androgenic steroids. Clin Ther. 2001;23: 1355–1390. Available: http://search.ebscohost.com/login.aspx?direct=true&db=cin20&AN=106844146&site=ehost-live
Severo CB, Ribeiro JP, Umpierre D, Da Silveira AD, Padilha MC, De Aquino Neto FR, et al. Increased atherothrombotic markers and endothelial dysfunction in steroid users. Eur J Prev Cardiol. 2013; 20: 195–201. doi:10.1177/2047487312437062
de Souza FR, Sales ARK, Dos Santos MR, Porello RA, Fonseca GWP da, Sayegh ALC, et al. Retrograde and oscillatory shear rate in young anabolic androgenic steroid users. Scand J Med Sci Sport. 2019;29: 422–429. doi:10.1111/sms.13332
Horwitz H, Andersen JT, Dalhoff KP. Health consequences of androgenic anabolic steroid use. J Intern Med. 2019;285: 333–340. doi:10.1111/joim.12850
Alhazmi N, Trotman CA, Finkelman M, Hawley D, Zoukhri D, Papathanasiou E. Salivary alkaline phosphatase activity and chronological age as indicators for skeletal maturity. Angle Orthod. 2019;89: 637–642. doi:10.2319/030918-197.1
Machado A, Maneiras R, Bordalo AA, Mesquita RBR. Monitoring glucose, calcium, and magnesium levels in saliva as a non-invasive analysis by sequential injection multi-parametric determination. Talanta. 2018;186: 192–199. doi:10.1016/j.talanta.2018.04.055
Hoseini A, Mirzapour A, Bijani A, Shirzad A. Salivary flow rate and xerostomia in patients with type I and II diabetes mellitus. Electron Physician. 2017;9: 5244–5249. doi:10.19082/5244
Castro-Silva II, Carvalho MAF, Basílio SR, Farias Júnior MVM, Maciel JAC. Relação Entre Alterações Salivares E Terapia Medicamentosa Em Adultos Jovens : Um Estudo Transversal Relation Between Salivary Alterations and Drug Therapy in Young Adults : a Cross - Sectional Study. Brazilian J Surg Clin Res. 2017;18: 17–24.
Kamalaksharappa SK, Rai R, Babaji P, Pradeep MC. Efficacy of probiotic and green tea mouthrinse on salivary pH. J Indian Soc Pedod Prev Dent. 2018. doi:10.4103/JISPPD.JISPPD_49_18
Woyceichoski IEC, Costa CH, de Araújo CM, Brancher JA, Resende LG, Vieira I, et al. Salivary buffer capacity, pH, and stimulated flow rate of crack cocaine users. J Investig Clin Dent. 2013. doi:10.1111/j.2041-1626.2012.00126.x
Rodrigues VP, Franco MM, Marques CPC, De Carvalho RCC, Leite SAM, Pereira ALA, et al. Salivary levels of calcium, phosphorus, potassium, albumin and correlation with serum biomarkers in hemodialysis patients. Arch Oral Biol. 2016;62: 58–63. doi:10.1016/j.archoralbio.2015.11.016
Alpdemir M, Eryilmaz M, Alpdemir MF, Topçu G, Azak A, Yücel D. Comparison of Widely Used Biochemical Analytes in the Serum and Saliva Samples of Dialysis Patients. J Med Biochem. 2018;37: 346–354. doi:10.1515/jomb-2017-0056
Parkinson AB, Evans NA. Anabolic androgenic steroids: A survey of 500 users. Med Sci Sports Exerc. 2006;38: 644–651. doi:10.1249/01.mss.0000210194.56834.5d
Rao A, Stahlman S, Hargreaves J, Weir S, Edwards J, Rice B, et al. Sampling Key Populations for HIV Surveillance: Results From Eight Cross-Sectional Studies Using Respondent-Driven Sampling and Venue-Based Snowball Sampling. JMIR Public Heal Surveill. 2017;3: e72. doi:10.2196/publichealth.8116
Hill SA, Waring WS. Pharmacological effects and safety monitoring of anabolic androgenic steroid use: differing perceptions between users and healthcare professionals. Ther Adv Drug Saf. 2019;10: 204209861985529. doi:10.1177/2042098619855291
Fudala PJ, Weinrieb RM, Calarco JS, Kampman KM, Boardman C. An Evaluation of Anabolic-Androgenic Steroid Abusers Over a Period of 1 Year: Seven Case Studies. Ann Clin Psychiatry. 2003;15: 121–130. doi:10.1023/A:1024640410093
Lundholm L, Frisell T, Lichtenstein P, Långström N. Anabolic androgenic steroids and violent offending: Confounding by polysubstance abuse among 10365 general population men. Addiction. 2015;110: 100–108. doi:10.1111/add.12715
Anabolic-steroid use, strength training, and multiple drug use among adolescents in the United States. Pediatrics. 1995;96: 23–28.
Elliot DL, Cheong J, Moe EL, Goldberg L. Cross-sectional study of female students reporting anabolic steroid use. Arch Pediatr Adolesc Med. 2007;161: 572–577. doi:10.1001/archpedi.161.6.572
Ip EJ, Barnett MJ, Tenerowicz MJ, Kim JA, Wei H, Perry PJ. Women and anabolic steroids: An analysis of a Dozen users. Clin J Sport Med. 2010;20: 475–481. doi:10.1097/JSM.0b013e3181fb5370
Yesalis CE, Kennedy NJ, Kopstein AN, Bahrke MS. Anabolic-Androgenic Steroid Use in the United States. JAMA J Am Med Assoc. 1993;270: 1217–1221. doi:10.1001/jama.1993.03510100067034
Sader MA, Griffiths KA, McCredie RJ, Handelsman DJ, Celermajer DS. Androgenic anabolic steroids and arterial structure and function in male bodybuilders. J Am Coll Cardiol. 2001;37: 224–230. doi:10.1016/S0735-1097(00)01083-4
Rasmussen JJ, Schou M, Selmer C, Johansen ML, Gustafsson F, Frystyk J, et al. Insulin sensitivity in relation to fat distribution and plasma adipocytokines among abusers of anabolic androgenic steroids. Clin Endocrinol (Oxf). 2017;87: 249–256. doi:10.1111/cen.13372
Venâncio D, Nóbrega A. Avaliação descritiva sobre o uso de esteroides anabolizantes e seu efeito sobre as variáveis bioquímicas e neuroendócrinas em indivíduos que praticam exercício. Rev bras med …. 2010;16: 191–195. Available:http://bases.bireme.br/cgibin/wxislind.exe/iah/online/?IsisScript=iah/iah.xis&src=google&base=LILACS&lang=p&nextAction=lnk&exprSearch=551078&indexSearch=ID
Kirchherr J, Charles K. Enhancing the sample diversity of snowball samples: Recommendations from a research project on anti-dam movements in Southeast Asia. PLoS One. 2018;13: 1–17. doi:10.1371/journal.pone.0201710
Copeland J, Peters R, Dillon P. Anabolic-androgenic steroid use disorders among a sample of Australian competitive and recreational users. Drug Alcohol Depend. 2000;60: 91–96. doi:10.1016/S0376-8716(00)80011-3
Skåberg K, Nyberg F, Engström I. The development of multiple drug use among anabolic-androgenic steroid users: Six subjective case reports. Subst Abus Treat Prev Policy. 2008;3: 1–10. doi:10.1186/1747-597X-3-24
Etikan I. Sampling and Sampling Methods. Biometrics Biostat Int J. 2017;5: 215–217. doi:10.15406/bbij.2017.05.00149
ABEP AB de E de P. Critério de classificação econômica Brasil. 2018.
Hartgens F, Rietjens G, Keizer HA, Kuipers H, Wolffenbuttel BHR. Effects of androgenic-anabolic steroids on apolipoproteins and lipoprotein (a). Br J Sports Med. 2004;38: 253–259. doi:10.1136/bjsm.2003.000199
Ebenbichler CF, Sturm W, Gänzer H, Bodner J, Mangweth B, Ritsch A, et al. Flow-mediated, endothelium-dependent vasodilatation is impaired in male body builders taking anabolic-androgenic steroids. Atherosclerosis. 2001. doi:10.1016/S0021-9150(01)00465-8
Vilar Neto J de O, da Silva CA, Lima AB, Caminha J de SR, Pinto DV, Alves FR, et al. Disorder of hypothalamic–pituitary–gonadal axis induced by abusing of anabolic–androgenic steroids for short time: A case report. Andrologia. 2018;50: 1–4. doi:10.1111/and.13107
Fregoneze AP, De Oliveira Lira Ortega A, Brancher JA, Vargas ET, De Paula Meneses R, Bönecker MJS. Sialometric analysis in young patients with chronic renal insufficiency. Spec Care Dent. 2013. doi:10.1111/scd.12008
De Campos DR, Yonamine M, Alves MJDNN, Moreau RLDM. Determinação de esteróides androgênicos anabólicos em urina por cromatografia gasosa acoplada à espectrometria de massas. Rev Bras Ciencias Farm J Pharm Sci. 2005;41: 467–476. doi:10.1590/s1516-93322005000400009
Bick. Hematology: clinical and laboratory practice. Bick RL, editor. St Louis: Mosby Inc; 1993.
Oliveira JEP de, Júnior RMM, Vencio S. Diretrizes 2017-2018. 2018. Available: https://www.diabetes.org.br/profissionais/images/2017/diretrizes/diretrizes-sbd-2017-2018.pdf
Beckman Coulter I. Beckman Coulter, Inc. In: https://www.beckmancoulter.com/en/support [Internet]. 2020 [cited 25 Jan 2020]. Available: https://www.beckmancoulter.com/
Siemens Healthcare Diagnósticos S.A. Siemens Healthcare Diagnósticos. In: https://www.siemens-healthineers.com/br/support-documentation/online-services/document-library [Internet]. 2020 [cited 25 Jan 2020]. Available: https://www.siemens-healthineers.com/br
Brasileiro C. Normatização da Determinação Laboratorial do Perfil Lipídico Consenso Brasileiro para a Normatização da Determinação Laboratorial do Perfil Lipídico Recomendações para o atendimento do paciente no Laboratório clínico. Normatização da Determ Lab do Perf Lipídico Consenso Bras para a Normatização da Determ Lab do Perf Lipídico Recom para o atendimento do paciente no Laboratório clínico. 2017;1.13: 1–5.
Pierre G, Ciriades J. Manual de Patologia Clínica - Ciriades. Atheneu; 2009.
Pearson TA, Mensah GA, Alexander RW, Anderson JL, Cannon RO, Criqui M, et al. Markers of inflammation and cardiovascular disease: Application to clinical and public health practice: A statement for healthcare professionals from the centers for disease control and prevention and the American Heart Association. Circulation. 2003;107: 499–511. doi:10.1161/01.CIR.0000052939.59093.45
Basílio ILD, Matos APR, Parente GVU, Oliveira JM. Análise do líquido ascítico de pacientes portaores de doença hepática. Rev Saúde e Ciência. 2016;5: 23–36.
Wu AHB. Tietz Clinical Guide to Laboratory Tests. 2006. Available: https://books.google.com/books?hl=en&lr=&id=aQqjBQAAQBAJ&pgis=1
Couto JJA de M, Lopes FFF. A influência da faixa etária na velocidade do fluxo salivar em adultos. Rfo Upf. 2010;15: 135–138. Available: http://revodonto.bvsalud.org/scielo.php?script=sci_arttext&pid=S1413-40122010000200007&lng=es&nrm=iso
Adilson A, Lima S De, Antonia M, Figueiredo Z De, Maria S, Krapf R, et al. Salivary flow rate and pH after radiotherapy of the head and neck region. 2004; 50:287–293. Available:http://www.inca.gov.br/rbc/n_50/v04/pdf/artigo2.pdf
Al-Rawi NH, Shahid AM. Oxidative stress, antioxidants, and lipid profile in the serum and saliva of individuals with coronary heart disease: Is there a link with periodontal health? Minerva Stomatol. 2017;66: 212–225. doi:10.23736/S0026-4970.17.04062-6
Schützemberger E, Souza T, Petruccix E, Machado N, Armando J. Análise bioquímica do fluido salivar de indivíduos portadores de doença periodontal Biochemical analysis of saliva of subjects with periodontal disease. Rsbo. 2007;43.
Tiongco REG, Arceo ES, Rivera NS, Flake CCD, Policarpio AR. Estimation of salivary glucose, amylase, calcium, and phosphorus among non-diabetics and diabetics: Potential identification of non-invasive diagnostic markers. Diabetes Metab Syndr Clin Res Rev. 2019;13: 2601–2605. doi:10.1016/j.dsx.2019.07.037
Savkovic S, Lim S, Jayadev V, Conway A, Turner L, Curtis D, et al. Urine and Serum Sex Steroid Profile in Testosterone-Treated Transgender and Hypogonadal and Healthy Control Men. J Clin Endocrinol Metab. 2018;103: 2277–2283. doi:10.1210/jc.2018-00054
Silva GG, Brito A de F, Nogueira FR de S, Júnior JFCR, Ribeiro SLG, Oliveira CVC de, et al. Prevalência do uso de esteroides anabólicos androgênicos em praticantes de musculação de Teresina-PI. Rev Port Ciências do Desporto. 2017;2017: 115–124. doi:10.5628/rpcd.17.s4a.115
Frizon F, Macedo SMD, Yonamine M. Uso de esteróides andrógenos anabólicos por praticantes de atividade física das principais academias de Erechim e Passo Fundo/RS. Rev Ciencias Farm Basica e Apl. 2005;26: 227–232.
Salim O, Abrahin C, Stefanie N, Souza F, Corrêa De Sousa E, Kely J, et al. Prevalência do uso e conhecimento de esteroides anabolizantes androgênicos por estudantes e professores de educação física que atuam em academias de ginástica. Rev Bras Med Esporte. 2013;19: 27–30.
Paul O. Prevention of cardiovascular disease. Prev Med (Baltim). 2007;2: 473–479. doi:10.1016/0091-7435(73)90043-1
Hero C, Karlsson SA, Franzén S, Svensson A-M, Miftaraj M, Gudbjörnsdottir S, et al. Adherence to lipid- lowering therapy and risk for cardiovascular disease and death in type 1 diabetes mellitus : a based study from the Swedish National Diabetes Register. 2020; 1–9. doi:10.1136/bmjdrc-2019-000719
Cheung MC, Albers JJ, Wahl PW, Hazzard WR. High density lipoproteins during hypolipidemic therapy. A comparative study of four drugs. Atherosclerosis. 1980;35: 215–228. doi:10.1016/0021-9150(80)90121-5
Vega GL, Clarenbach JJ, Dunn F, Grundy SM. Oxandrolone enhances hepatic ketogenesis in adult Men. J Investig Med. 2008;56: 920–924. doi:10.2310/JIM.0b013e318189153d
Davis SM, Cox-Martin MG, Bardsley MZ, Kowal K, Zeitler PS, Ross JL. Effects of oxandrolone on cardiometabolic health in boys with klinefelter syndrome: A randomized controlled trial. J Clin Endocrinol Metab. 2017;102: 176–184. doi:10.1210/jc.2016-2904
Graham MR, Davies B, Grace FM, Kicman A, Baker JS. Anabolic steroid use: Patterns of use and detection of doping. Sport Med. 2008;38: 505–525. doi:10.2165/00007256-200838060-00005
Storer TW, Magliano L, Woodhouse L, Lee ML, Dzekov C, Dzekov J, et al. Testosterone dose-dependently increases maximal voluntary strength and leg power, but does not affect fatigability or specific tension. J Clin Endocrinol Metab. 2003. doi:10.1210/jc.2002-021231
Souza FR de, Dos Santos MR, Porello RA, Fonseca GWP da, Sayegh ALC, Lima TP, et al. Diminished cholesterol efflux mediated by HDL and coronary artery disease in young male anabolic androgenic steroid users. Atherosclerosis. 2019;283: 100–105. doi:10.1016/j.atherosclerosis.2019.02.006
Faludi A, Izar M, Saraiva J, Chacra A, Bianco H, Afiune Neto A, et al. Atualização Da Diretriz Brasileira De Dislipidemias E Prevenção Da Aterosclerose - 2017. Arq Bras Cardiol. 2017;109. doi:10.5935/abc.20170121
Arazi H. Effects of longitudinal abuse of anabolic steroids on liver enzymes activity and lipid profiles of male bodybuilders. Prog Nutr. 2018;20: 323–328. doi:10.23751/pn.v20i3.5287
Vanbberg P, Atar D. Androgenic Anabolic Steroid Abuse and the Cardiovascular System. 1st ed. In: Thieme D, Hemmersbach P, editors. Doping in Sports, Handbook of Experimental Pharmacology. 1st ed. Berlin Heidelberg: Springer Berlin Heidelberg; 2010. pp. 411–457. doi:10.1007/978-3-540-79088-4
Sullivan ML, Martinez CM, Gennis P, Gallagher EJ. The cardiac toxicity of anabolic steroids. Prog Cardiovasc Dis. 1998. doi:10.1016/S0033-0620(98)80019-4
Rosca AE, Stancu CS, Badiu C, Popescu BO, Mirica R, Căruntu C, et al. Lipid profile changes induced by chronic administration of anabolic androgenic steroids and taurine in rats. Med. 2019;55. doi:10.3390/medicina55090540
Glueck CJ, Ford S, Steiner P, Fallat R. Triglyceride removal efficiency and lipoprotein lipases: Effects of oxandrolone. Metabolism. 1973;22: 807–814. doi:10.1016/0026-0495(73)90051-6
Glazer G. Atherogenic Effects of Anabolic Steroids on Serum Lipid Levels: A Literature Review. Arch Intern Med. 1991;151: 1925–1933. doi:10.1001/archinte.1991.00400100013003
Herlitz LC, Markowitz GS, Farris AB, Schwimmer JA, Stokes MB, Kunis C, et al. Development of Focal Segmental Glomerulosclerosis after Anabolic Steroid Abuse. J Am Soc Nephrol. 2010;21: 163–172. doi:10.1681/asn.2009040450
Westlye LT, Kaufmann T, Alnæs D, Hullstein IR, Bjørnebekk A. Brain connectivity aberrations in anabolic-androgenic steroid users. NeuroImage Clin. 2017;13: 62–69. doi:10.1016/j.nicl.2016.11.014
Pereira E, Moyses SJ, Ignácio SA, Mendes DK, Da Silva DS, Carneiro E, et al. Prevalence and profile of users and non- users of anabolic steroids among resistance training practitioners. BMC Public Health. 2019;14: 1–8. doi:10.1371/journal.pone.0223384
Smit DL, de Ronde W. Outpatient clinic for users of anabolic androgenic steroids: An overview. Neth J Med. 2018;76: 167–175.
Schwingel PA, Cotrim HP, Salles BR, Almeida CE, Dos Santos CR, Nachef B, et al. Anabolic-androgenic steroids: A possible new risk factor of toxicant-associated fatty liver disease. Liver Int. 2011;31: 348–353. doi:10.1111/j.1478-3231.2010.02346.x

Complementarymethodology.docx

Download PDF

Version 1

posted

You are reading this latest preprint version

Oxandrolone Use Causes Dyslipidemia in Resistance-Training Practitioners

Status:

Version 1

Abstract

Figures

Background

Goals

Methods

Study Design

Ethical Procedures

Inclusion and exclusion criteria

Sample selection

Sample collection timepoints

Blood collection and analyses

Saliva collection and analyses

Urine collection and AAS Screening

Statistical analysis

Results

Discussion

Conclusions

Abbreviations

Declarations

Ethics approval and consent to participate:

Consent for publication:

Availability of data and materials

Competing interests

Funding

Author’s contributions

Acknowledgements

References

Supplementary Files

Status:

Version 1