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    RADIATION RESEARCH 169, 337343 (2008)0033-7587/08 $15.00 2008 by Radiation Research Society.All rights of reproduction in any form reserved.

    Influence of Electromagnetic Fields Emitted by GSM-900 CellularTelephones on the Circadian Patterns of Gonadal, Adrenal and

    Pituitary Hormones in Men

    Yasmina Djeridane,a Yvan Touitoua,1 and Rene de Sezeb

    a Faculte de Medecine Pierre et Marie Cur ie, Service de Biochi mie Medicale et Bio logie Moleculaire, INSERM U713, 75013, Paris, F rance; andb Unite de Toxicologie Experimentale et Predictive, INERIS, Parc technologique ALATA, 6055 0 Verneuil-en-Halatte, France

    Djeridane, Y., Touitou, Y. and de Seze, R. Influence of Elec-

    tromagnetic Fields Emitted by GSM-900 Cellular Telephones

    on the Circadian Patterns of Gonadal, Adrenal and PituitaryHormones in Men. Radiat. Res. 169, 337343 (2008).

    The potential health risks of radiofrequency electromag-

    netic fields (RF EMFs) emitted by mobile phones are cur-

    rently of considerable public interest. The present study in-vestigated the effect of exposure to 900 MHz GSM radiofre-

    quency radiation on steroid (cortisol and testosterone) andpituitary (thyroid-stimulating hormone, growth hormone,

    prolactin and adrenocorticotropin) hormone levels in 20

    healthy male volunteers. Each subject was exposed to RFEMFs through the use of a cellular phone for 2 h/day, 5 days/

    week, for 4 weeks. Blood samples were collected hourly duringthe night and every 3 h during the day. Four sampling sessions

    were performed at 15-day intervals: before the beginning of

    the exposure period, at the middle and the end of the exposure

    period, and 15 days later. Parameters evaluated included themaximum serum concentration, the time of this maximum,and the area under the curve for hormone circadian patterns.

    Each individuals pre-exposure hormone concentration wasused as his control. All hormone concentrations remained

    within normal physiological ranges. The circadian profiles of

    prolactin, thyroid-stimulating hormone, adrenocorticotropinand testosterone were not disrupted by RF EMFs emitted by

    mobile phones. For growth hormone and cortisol, there weresignificant decreases of about 28% and 12%, respectively, in

    the maximum levels when comparing the 2-week (for growth

    hormone and cortisol) and 4-week (for growth hormone) ex-posure periods to the pre-exposure period, but no difference

    persisted in the postexposure period. Our data show that the900 MHz EMF exposure, at least under our experimental con-

    ditions, does not appear to affect endocrine functions in men.2008 by Radiation Research Society

    INTRODUCTION

    Epidemiological studies and others (1, 2) have enabledinternational bodies such as the International Commission

    1 Address for correspondence: Faculte de Medecine Pierre et MarieCurie, Service de Biochimie Medicale et Biologie Moleculaire, INSERMU713, 91, Boulevard de lHopital, 75013, Paris, France; e-mail:[email protected].

    on Non-Ionizing Radiation Protection and the EuropeanCommission to establish recommendations for public ex-posure to EMFs to ensure a high level of safety (3). Theextensive use of mobile phones has been accompanied by

    public debate about possible adverse effects on humanhealth. However, there is experimental evidence to showthat 900 MHz EMFs do not affect levels of melatonin inhumans (4, 5) and rodents (69), 6-sulfatoxymelatonin inrats (10), cortisol in humans (5, 11), and some pituitaryhormones such as thyroid-stimulating hormone (TSH)growth hormone (GH), prolactin (PRL), luteotropic hormone (LH), follicle-stimulating hormone (FSH) and adrenocorticotropin (ACTH) in humans (7, 12). Other studiesusing rats report a decrease in the levels of the pituitaryhormones TSH, LH and FSH (13, 14) as well as testoster-one (14). The purpose of the present study was to examinethe effect of 900 MHz radiofrequency (RF) EMFs emittedby GSM mobile telephones on the circadian patterns osteroid (cortisol and testosterone) and pituitary (TSH, GHPRL and ACTH) hormones in healthy men.

    MATERIALS AND METHODS

    Subjects

    Twenty healthy male volunteers who were 2032 years old participatedin this study. Their health status was ascertained by both clinical androutine biological examinations. The main exclusion criteria were nightor shift work, stressful work, frequent exposure to unusually high-inten-sity electromagnetic fields at any frequency (static, extremely low-frequency or RF), mobile phone use prior to entering the study and during

    the study other than that prescribed by the study, diseases of the ear, noseand throat, endocrine disorders, neuropsychiatric disease, unusual sleeppatterns, and recent transcontinental flight. The protocol was approved bythe Ethics Committee of Nmes University Hospital and was performedaccording to ethical guidelines dealing with research on biologicarhythms in humans (15).

    Exposure Parameters

    The phone tested was the Motorola 8200 cellular radiotelephone, whichoperates near 900 MHz and employs the GSM system (Global Systemfor Mobile communication), 217 Hz modulation frequency, 1/8 duty fac-tor, 2 W maximal peak power, corresponding to a time-averaged absorbedpower (specific absorption rate averaged over 10 g, SAR10g) in the tem

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    338 DJERIDANE, TOUITOU AND de SEZE

    FIG. 1. Experimental design.

    poral brain of about 0.3 W/kg. For each subject, exposure was on thesame side of the head for all sessions.

    Phone Exposure

    Volunteers used GSM phones for 2 h/day, 5 days/week, for 4 weeks. Eachsubject was exposed in our laboratory in either the 14:0016:00 h or 16:3018:30 h period. All the subjects were tested within a 3-month period. Fivegroups of four subjects were exposed at the same time during each session.During the exposure sessions, the attention of the volunteers and a correctusual listening position were maintained by TV projection of movies. Movieswere selected to avoid boring presentations, excessive suspense, dramatic

    killing, exciting sexuality, or depressing morbidity. For tests, the audio signalfrom the television set was distributed to four fixed telephones of the con-ventional commuted network. This enabled each subject to call a receivingtelephone from his own GSM handset to hear the movie soundtrack. Toreproduce the same behavioral conditions on all the sampling days, a shamexposure was also performed on the days of the first and the last blooddrawing sessions at the same times as the actual exposures. For sham ex-posure, the radiofrequency output on these days was switched to a 50

    non-emitting load instead of the antenna. In this case, movie sound was hearddirectly from the TV speakers.

    Sampling Protocol

    Volunteers went to the Clinical Research Center of the Hospital for thesampling sessions. They were there for 24 h and arrived at around 18:30

    h. After 15 min of rest, their blood samples were collected through anindwelling antecubital catheter hourly between 22:00 and 10:00 h andevery 3 h between 10:00 and 22:00 h, for a total of 17 samples over 24h. Volunteers had dinner at 20:00 h and went to bed at 22:45 h. Duringthe sampling sessions, volunteers were synchronized photically by a reg-ular light pattern (on at 07:00 h, off at 23:00 h). Night samplings wereperformed under moderate light (intensity less than 10 lux). Volunteersusually remained asleep during samplings, but arousal sometimes oc-curred depending on the depth of sleep and position of the catheterizedarm. Data acquisition occurred over four sessions. The first took placebefore the beginning of the listening sessions (pre-exposure period); thenext was performed at the middle of the 1-month listening period (secondweek of exposure period). The third took place at the end of the listeningperiod (fourth week of exposure period), and the last 15 days later eval-

    uated the retentivity of any potential effect or a rebound effect (postex-

    posure period).Figure 1 shows the experimental design.

    Biochemical Assays

    Serum levels of cortisol, testosterone, TSH, GH, PRL and ACTH wereassayed using commercial immunofluorometry (Delphia, Wallac, Fin-

    land). The intra-assay coefficients of variation were as follows: for cor-tisol, 2.2% at 400 ng/ml; for testosterone, 4.5% at 4 ng/ml; for TSH,

    4.5% at 1.05 IU/ml; for GH, 6% at 0.40 mIU/liter; for PRL, 7.4% at11.7 ng/ml; for ACTH, 6.2% at 20 pmol/liter.

    Variables

    The following variables were analyzed for each individual volunteerand for each of the four sampling sessions: the maximum of the 24-h

    serum concentrations, the time of this peak (closest integer clock time),and the area under the curve. The area under the curve was calculated

    with Prism v3.00 (GraphPad).

    Statistical Analysis

    To obtain high sensitivity in view of possible wide interindividual var-iations, subjects were their own controls, using the pre-exposure session

    for reference. The means SD for each variable (peak serum concen-tration, time of this peak, and area under the curve) were calculated foreach session, and the 2-week, 4-week and postexposure sessions were

    compared with the pre-exposure session. The non-parametric Friedmanstest was performed to evaluate whether and to what extent exposure af-

    fects hormone levels. The analysis factor was the period pre-exposure,2-week or 4-week exposure, or postexposure; when appropriate, the post

    hoc Dunns Multiple Comparison Test was performed for more precise

    comparison between specific periods. The Friedmans test was performed

    with Prism v3.00 (GraphPad). Reported differences are the relative dif-

    ferences expressed as percentages of the mean values for the 19 volun-

    teers at the time when the change was considered to the mean value of

    the 19 volunteers at the indicated period. When not otherwise mentioned,

    the reference period is the pre-exposure period.

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    339900 MHz ELECTROMAGNETIC FIELD AND CIRCADIAN HORMONE SECRETION

    FIG. 2. Circadian patterns of ACTH, cortisol and testosterone for each session. Each point is the mean hormone

    concentration standard error of the mean of 19 subjects shown before, during and after a 4-week exposure period.

    RESULTS

    One volunteer had to be excluded from the analysis be-cause his hormone profile indicated that he did not adhere tothe normal daytime schedule. Thus the total number of vol-unteers for the analysis was 19. All hormone profiles re-mained within normal physiological ranges; their circadianprofiles are presented in Figs. 2 and 3. For cortisol and GH,we observed a significant decrease in the maximum of the

    peak. For GH, this was correlated with a decrease in the areaunder the curve. No time of the peak in the serum hormoneconcentrations was significantly different over the 4-weeksampling period (Table 1 and Figs. 2, 3).

    ACTH

    ACTH concentrations showed a morning peak, with themaximum serum ACTH level occurring between 07:00 h

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    FIG. 3. Circadian patterns of TSH, GH and PRL for each session. Each point is the mean hormone concentration standard error of the mean of 19 (for TSH and GH) or 18 (for PRL) subjects shown before, during and after a4-week exposure period.

    and 08:00 h (Fig. 2). The only significant difference ap-peared in the Friedmans test for the area under the curve(P 0.043), a 10.1% increase when the intraindividualcoefficient of variation is 18%. Since the post test showsthat this difference mainly affects the comparison betweenthe pre-exposure and the postexposure sessions, we cannot

    consider this as an effect of the exposure. There was alsoa nonsignificant difference in the area under the curve aswell in the peak time: 1.2 h earlier for the 4-week exposuresession compared to the pre-exposure session, when theaverage intraindividual variation was 1.9 h. The largest dif-ference in the maximum was a nonsignificant 5.6% increase

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    341900 MHz ELECTROMAGNETIC FIELD AND CIRCADIAN HORMONE SECRETION

    TABLE 1

    Area under the Curve, Peak Time and Peak Value Analyzed by using the Friedmans Test over the

    Pre-exposure to Postexposure Periods

    Hormone Measurement Pre-exposure 2-week exposure 4-week exposure Postexposure

    ACTH Area under the cur ve (pmol/liter h) 441 191 482 227 470 195 490 212Peak time (h) 7.5 1.7 7.1 1.0 6.3 2.0 7.7 2.7

    Peak value (pmol/liter) 33

    14 35

    10 35

    10 33

    12Cortisol Area under the curve (ng/ml h) 1200 460 1100 310 1200 280 1200 330Peak time (h) 8.1 1.6 7.2 2.4 7.5 1.3 8.2 1.4Peak value (ng/ml) 98 30 88 24* 100 23 105 17

    Testosterone Area under the curve (ng/ml h) 123 36 125 36 125 35 135 23Peak time (h) 3.1 1.2 3.1 1.0 3.1 2.1 3.1 1.1Peak value (ng/ml) 4.9 1.4 5.0 1.0 5.0 1.2 5.2 0.9

    TSH Area under the curve (IU/ml h) 40 13 38 13 38 15 34 12Peak time (h) 1.0 2.8 0.3 2.9 1.3 3.2 0.0 3.2Peak value (IU/ml) 2.3 1.1 2.3 1.0 2.4 0.7 2.2 1.3

    GH Area under the curve (mIU/liter h) 102 61 84 60* 86 69 90 70Peak time (h) 1.5 2.1 1.5 2.1 1.5 2.0 1.5 2.1Peak value (m IU/liter) 29 14 23 15* 22 16* 25 17

    PRL Area under the curve (ng/ml h) 195 46 202 46 224 65 204 58Peak time (h) 4.2 3.9 4.1 4.7 4.6 3.0 5.0 4.7Peak value (ng/ml) 11 5 11 4 12 3 12 4

    Notes. Values are shown as means SD. Area under the curve: *P 0.013: 2-week exposure compared to pre-exposure for GH. Peak value: * P 0.025: 2-week exposure compared to pre-exposure for cortisol; *P 0.003: 2-week and 4-week exposure compared to pre-exposure for GH.

    for the 4-week exposure session, when the intraindividualcoefficient of variation was 20%.

    Cortisol

    The pattern of serum cortisol paralleled that of ACTH(Fig. 2). The largest change observed in the area under thecurve was a nonsignificant 6.2% decrease for the 2-weekexposure session. The largest difference in the average peaktime was a nonsignificant earlier peak time of0.8 h forthe 2-week exposure session compared with the averageintraindividual variation of 1.7 h. A significant differencein the maximum secretion of cortisol was found with theFriedmans test (P 0.025); the largest change was a 12%decrease for the 2-week exposure session compared to thepre-exposure session, but the post hoc Dunns MultipleComparison Test did not show any more significant differ-ence between those two periods. For comparison, the intra-individual variation was 12.8%.

    Testosterone

    The Friedmans test did not indicate a statistically sig-nificant effect of EMFs on testosterone secretion (Fig. 2).The largest difference in the area under the curve was anonsignificant 1% increase for the postexposure sessioncompared with an average intraindividual variation of 18%.The largest change in average peak time was a nonsignif-icant delay of 0.5 h for the 2-week exposure session com-pared with average intraindividual variations of 0.23 h. Thelargest change in peak testosterone levels was a nonsignif-icant 5% increase for the postexposure session, whereas therelative intraindividual variation was 27%.

    TSH

    The maximum peak TSH value was observed at around23:00 h. There was no significant difference in the areaunder the curve, the time of the peak, or the maximum (Fig3). The largest difference in the area under the curve wasa nonsignificant decrease of 12.6% for the postexposuresession, when the intraindividual coefficient of variationwas 16%. The largest difference in the peak time was anonsignificant earlier time peak of1.1 h on the postex-posure session, when the average intraindividual variationwas 2.8 h. The largest difference in the maximum was anonsignificant 13.1% decrease for the postexposure sessionwhen the intraindividual coefficient of variation was 24%

    GH

    The circadian rhythm of GH concentrations was clearlyvisible. The maximum serum GH level occurred during theearly night at around 01:00 h (Fig. 3). The largest differ-ence in the area under the curve was a decrease of 17.3%for the 2-week exposure session (P 0.013), when theintraindividual coefficient of variation was 31.1%. The largest difference in the nocturnal peak time was a nonsignif-icantly earlier time of 0.1 h for the 4-week exposure ses-sion. This difference cannot be significant with such a largeaverage intraindividual variation of 1.84 h. Significant dif-ferences (P 0.003) were observed in the values of themaximum for the 2-week exposure session (Dunn: difference in rank sum: 27; P 0.01) as for the 4-week exposuresessions compared to the pre-exposure session (Dunn: difference in rank sum: 24; P 0.05). The intensity of thisdecrease was about 27 to 29%, when the intraindividua

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    342 DJERIDANE, TOUITOU AND de SEZE

    coefficient of variation was 34.8%. This decrease was cor-related with a nonsignificant 12 to 17% decrease in the areaunder the curve.

    PRL

    One volunteer presented with stomach spasms for the4-week exposure session and was given metoclopramid,which is known to cause an increased secretion of PRL.Thus this volunteer was removed from the analysis, leaving18 volunteers for the analysis of PRL. There were no dif-ferences in PRL concentrations between the pre-exposedand exposed subjects (Fig. 3). The largest difference in thearea under the curve was a nonsignificant 9.3% increase onthe 4-week exposure session, when the intraindividual co-efficient of variation was 9%. The largest difference in thepeak time was a nonsignificant later time peak of 0.8 h inthe postexposure session, when the average of intraindivid-ual variation was 2.8 h. The largest difference in the max-

    imum was a nonsignificant 3.9% increase on the 4-weekexposure session, correlated to the increase in the area un-der the curve, when the intraindividual coefficient of vari-ation was 16%.

    DISCUSSION

    Radiofrequency-radiation exposure can be harmful be-cause of its ability to heat biological tissue (16). We studiedthe effects of 900 MHz GSM EMFs on the circadian pat-terns of serum steroid (cortisol and testosterone) and pitu-itary (TSH, GH, PRL, and ACTH) hormones in healthymale subjects from exposure levels that would not heat tis-

    sue. All hormones remained within the normal physiolog-ical range throughout and after exposure of healthy men toEMFs emitted by cellular phones 2 h/day, 5 days/week, for4 weeks. Also, exposure did not affect the serum levels ofany of the hormones tested. The hormone concentrationsremained within normal physiological ranges (1721). Inaddition, no significant effects were found on PRL, TSHand ACTH with respect to the dynamic characteristics ofthe circadian blood level profiles. The circadian hormonepatterns were in agreement with those reported in otherstudies (1721), but we found significant decreases of about28% and 12% in the peak secretion of GH and cortisol,respectively. For cortisol, the decrease was significant whencomparing the 2-week exposure session to the pre-exposuresession. Such a small decrease (12%) in the circadian am-plitude is unlikely to be indicative of a health risk. Inter-estingly, it has been shown elsewhere that salivary and se-rum cortisol levels in humans (5, 11) were independent ofthe EMF exposure. For GH, the decrease in the maximumlevel was correlated with a nonsignificant 12 to 17% de-crease in the area under the curve. Our data on the circadianprofiles of pituitary hormone concentrations are in agree-ment with those of de Seze et al. (12) and Mann et al. (7),who reported that 900 MHz EMFs did not affect daytime

    serum concentrations of the pituitary hormones ACTH,TSH, GH, PRL, LH and FSH. For the small changes ob-served in GH and cortisol, a counterbalanced exposure de-sign with 2 weeks of exposure in each phase would allowus to detect the extent to which the subjects acclimatizedto the exposure and whether exposure order could be a

    source of variability; however, this would have decreasedthe number of exposure sessions and the total exposure du-ration, which could have led to no effect. Thus further stud-ies are needed.

    Changes that could be considered biologically relevantare of the order of the average relative spontaneous varia-tion of an individuals value from one session to another.With 19 values, as in our study, such a change is of theorder of the standard deviation of values between individ-uals. This is also the amplitude of the difference that wouldbe needed to reach a power of 80% for this study. Theobserved changes are far below this value, which meansthat mobile phone exposure does not alter the blood con-

    centrations of most of the hormones studied.There are currently no data on the effects of RF EMFson reproductive function in men. In contrast to a study thatreported that 900 MHz RF EMFs induced a significant de-crease in total serum testosterone levels in rats (14), thepresent study found no difference. It is possible that thedifference in the effects observed in rodents and humansmay be because that animals detect and perceive magneticfields differently (22) or are not affected in the same way.

    In conclusion, our data indicate that mobile phones emit-ting 900 MHz EMFs do not induce any modification ofeither hormone concentrations or circadian patterns (nomodification of the shape of the curve: neither phase ad-

    vance nor phase delay), except for cortisol and GH, wherewe observe a significant decrease in the maximum of thepeak when comparing the 2-week (for growth hormone andcortisol) and 4-week (for growth hormone) exposure peri-ods to the pre-exposure period, but no difference persistedin the postexposure period. The results also suggest that the900 MHz EMF exposure, at least under our experimentalconditions, does not appear to affect human endocrine func-tions, which is in good agreement with the inconsistent re-sults obtained in some epidemiological studies (1, 2).Though our experiment was performed with a long durationof exposure, it cannot be ruled out that repetitive exposuresfor a year or more may have effects on humans, especially

    on young teenagers who use phones for several hours perday.

    ACKNOWLEDGMENTS

    This work has been funded by Motorola, Inc.

    Received: December 8, 2006; accepted: October 9, 2007

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