title: Urinary paraben concentrations and ovarian aging among women from a fertility center.
abstract: BACKGROUND
  Parabens are preservatives commonly used in personal care products, pharmaceuticals, and foods. There is documented widespread human exposure to parabens, and some experimental data suggest that they act as estrogenic endocrine disruptors. As far as we are aware, no epidemiologic studies have assessed female reproductive health effects in relation to paraben exposure.
  
  
  OBJECTIVE
  We examined the association of urinary paraben concentrations with markers of ovarian reserve in a prospective cohort study of women seeking fertility treatment at Massachusetts General Hospital, Boston, Massachusetts.
  
  
  METHODS
  Measures of ovarian reserve were day-3 follicle-stimulating hormone (FSH), antral follicle count (AFC), and ovarian volume. Paraben concentrations [methylparaben (MP), propylparaben (PP), and butylparaben (BP)] were measured in spot urine samples collected prior to the assessment of outcome measures. We used linear and Poisson regression models to estimate associations of urinary paraben concentrations (in tertiles) with ovarian reserve measures.
  
  
  RESULTS
  Of the women enrolled in 2004-2010, 192 had at least one ovarian reserve outcome measured (mean age ± SD, 36.1 ± 4.5 years; range, 21.0-46.7 years). MP and PP were detected in > 99% of urine samples and BP in > 75%. We found a suggestive trend of lower AFC with increasing urinary PP tertiles [mean percent change (95% CI) for tertiles 2 and 3 compared with tertile 1, respectively, were -5.0% (-23.7, 18.4) and -16.3% (-30.8, 1.3); trend p-value (ptrend) = 0.07] as well as higher day-3 FSH with higher urinary PP tertiles [mean change (95% CI) for tertiles 2 and 3 compared with tertile 1 were 1.16 IU/L (-0.26, 2.57) and 1.02 IU/L (-0.40, 2.43); ptrend = 0.16]. We found no consistent evidence of associations between urinary MP or BP and day-3 FSH or AFC, or between urinary MP, PP, or BP and ovarian volume.
  
  
  CONCLUSIONS
  PP may be associated with diminished ovarian reserve. However, our results require confirmation in further studies.
authors.affiliation: Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts, USA.
authors.forename: Kristen W
authors.initials: KW
authors.lastname: Smith
authors.forename: Irene
authors.initials: I
authors.lastname: Souter
authors.forename: Irene
authors.initials: I
authors.lastname: Dimitriadis
authors.forename: Shelley
authors.initials: S
authors.lastname: Ehrlich
authors.forename: Paige L
authors.initials: PL
authors.lastname: Williams
authors.forename: Antonia M
authors.initials: AM
authors.lastname: Calafat
authors.forename: Russ
authors.initials: R
authors.lastname: Hauser
mesh_terms: D000328:Adult; D001900:Boston; D015331:Cohort Studies; D004781:Environmental Exposure / Q000032:analysis*; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D006801:Humans; D007247:Infertility, Female / Q000378:metabolism*; D016014:Linear Models; D010053:Ovary / Q000166:cytology / Q000187:drug effects* / Q000254:growth & development / Q000502:physiology; D010226:Parabens / Q000009:adverse effects / Q000032:analysis*; D011310:Preservatives, Pharmaceutical / Q000009:adverse effects / Q000032:analysis*; D011446:Prospective Studies; D014556:Urine / Q000737:chemistry*
chemical_list: D010226:Parabens; D011310:Preservatives, Pharmaceutical; C038091:butylparaben; D005640:Follicle Stimulating Hormone
references.citation: J Appl Toxicol. 2008 Jul;28(5):561-78
references.pmid: 18484575
references.citation: Int J Androl. 2010 Apr;33(2):385-93
references.pmid: 20002217
references.citation: Environ Health Perspect. 2012 Mar;120(3):464-70
references.pmid: 21900077
references.citation: Environ Health Perspect. 2010 May;118(5):679-85
references.pmid: 20056562
references.citation: J Chromatogr B Analyt Technol Biomed Life Sci. 2006 Nov 21;844(1):53-9
references.pmid: 16893688
references.citation: Reprod Toxicol. 2013 Jan;35:96-101
references.pmid: 22789395
references.citation: Environ Int. 2011 Jul;37(5):858-66
references.pmid: 21440302
references.citation: Crit Rev Toxicol. 2005 Jun;35(5):435-58
references.pmid: 16097138
references.citation: Environ Health Perspect. 2005 Nov;113(11):1530-5
references.pmid: 16263507
references.citation: Int J Androl. 2008 Apr;31(2):118-30
references.pmid: 18194284
references.citation: Environ Health Perspect. 2009 Apr;117(4):639-44
references.pmid: 19440505
references.citation: Menopause. 2008 Sep-Oct;15(5):857-61
references.pmid: 18427357
references.citation: Food Chem Toxicol. 2001 Dec;39(12):1225-32
references.pmid: 11696396
references.citation: Environ Health Perspect. 2011 Feb;119(2):252-7
references.pmid: 20876036
references.citation: J Vet Med Sci. 2002 Mar;64(3):227-35
references.pmid: 11999442
references.citation: Fertil Steril. 2008 Oct;90(4):911-40
references.pmid: 18929049
references.citation: Fertil Steril. 2001 Oct;76(4):666-9
references.pmid: 11591396
references.citation: Food Chem Toxicol. 2005 Jul;43(7):985-1015
references.pmid: 15833376
references.citation: Obstet Gynecol. 2011 Jul;118(1):63-70
references.pmid: 21691164
references.citation: Hum Reprod Update. 2003 Jul-Aug;9(4):359-72
references.pmid: 12926529
references.citation: Environ Health Perspect. 1998 Aug;106 Suppl 4:1051-8
references.pmid: 9703492
references.citation: Int J Toxicol. 2008;27 Suppl 4:1-82
references.pmid: 19101832
references.citation: Environ Health Perspect. 2012 Nov;120(11):1538-43
references.pmid: 22721761
references.citation: Environ Health Perspect. 2006 Dec;114(12):1843-6
references.pmid: 17185273
references.citation: Toxicol Appl Pharmacol. 1998 Nov;153(1):12-9
references.pmid: 9875295
references.citation: Environ Health Perspect. 2010 Jul;118(7):1039-46
references.pmid: 20308033
references.citation: Toxicol Sci. 2008 Nov;106(1):206-13
references.pmid: 18648085
references.citation: J Toxicol Environ Health A. 2005 Feb 27;68(4):239-51
references.pmid: 15799449
references.citation: Toxicol Mech Methods. 2010 Mar;20(3):105-11
references.pmid: 20163289
references.citation: Int J Dermatol. 1980 Nov;19(9):504-5
references.pmid: 6448825
references.citation: Fertil Steril. 2012 Jan;97(1):238-43
references.pmid: 22130324
references.citation: Annu Rev Physiol. 2005;67:285-308
references.pmid: 15709960
references.citation: Vital Health Stat 23. 2005 Dec;(25):1-160
references.pmid: 16532609
references.citation: Gynecol Endocrinol. 2005 Jul;21(1):33-7
references.pmid: 16048799
references.citation: J Steroid Biochem Mol Biol. 2002 Jan;80(1):49-60
references.pmid: 11867263
references.citation: Reprod Toxicol. 2010 Jun;29(3):306-16
references.pmid: 20132880