A role for female reproductive factors in the pathogenesis of thyroid autoimmunity has been suggested. This study investigated the prospective association between parity, abortion, use of oral contraceptive pill (OCP), and use of hormone replacement therapy (HRT), and 11-year change in serum thyrotropin (TSH), as well as change in thyroid peroxidase autoantibody (TPOAb) status.
Methods:
A random sample of 4649 people aged 18–65 years participated in a population-based study in the period 1997–1998. In the study presented here, 1749 non-pregnant women with no history of thyroid disease were included who participated in the 11-year follow-up examination in the period 2008–2010. Gynecological exposures were reported in a self-administered questionnaire at baseline and follow-up. TSH and TPOAb were measured at baseline and follow-up. Increased TPOAb status during follow-up was defined as a TPOAb below the assay cutoff (<30 kIU/L) at baseline and a TPOAb ≥30 kIU/L at follow-up. Multiple linear regression models were used, adjusted for age, smoking status, and urinary iodine excretion.
Results:
An inverse association was found between the number of years on HRT and the risk (odds ratio) of increased TPOAb status during follow-up (0.735 [confidence interval 0.558–0.968], p = 0.03). However, this association was not statistically significant when applying the Bonferroni adjusted significance level. The remaining reproductive factors showed no statistically significant association with risk of increased TPOAb during follow-up. Furthermore, parity, abortions, use of OCP, HRT use, age at menarche, and being pre- or postmenopausal were not significantly associated with 11-year TSH change.
Conclusions:
No statistically significant association was found between the studied female reproductive measures and 11-year risk of TSH or TPO change. A possible protective role for HRT in the etiology of thyroid autoimmunity, however, deserves further research.
Get full access to this article
View all access options for this article.
References
1.
BrixTH, HegedusL. 2011. The complexity of the etiology of autoimmune thyroid disease is gravely underestimated. Thyroid, 21:1289–1292.
BrixTH, HansenPS, KyvikKO, HegedusL. 2009. Aggregation of thyroid autoantibodies in twins from opposite-sex pairs suggests that microchimerism may play a role in the early stages of thyroid autoimmunity. J Clin Endocrinol Metab, 94:4439–4443.
4.
KrassasGE, PoppeK, GlinoerD. 2010. Thyroid function and human reproductive health. Endocr Rev, 31:702–755.
5.
LaurbergP, AndersenSL, Bülow PedersenI, AndersenS, CarleA. 2013. Screening for overt thyroid disease in early pregnancy may be preferable to searching for small aberrations in thyroid function tests. Clin Endocrinol (Oxf), 79:297–304.
6.
MullerAF, DrexhageHA, BerghoutA. 2001. Postpartum thyroiditis and autoimmune thyroiditis in women of childbearing age: recent insights and consequences for antenatal and postnatal care. Endocr Rev, 22:605–630.
7.
Stagnaro-GreenA. 2004. Postpartum thyroiditis. Best Pract Res Clin Endocrinol Metab, 18:303–316.
8.
Bülow PedersenI, LaurbergP, KnudsenN, JorgensenT, PerrildH, OvesenL, RasmussenLB. 2006. Lack of association between thyroid autoantibodies and parity in a population study argues against microchimerism as a trigger of thyroid autoimmunity. Eur J Endocrinol, 154:39–45.
9.
FriedrichN, RosskopfD, BrabantG, VolzkeH, NauckM, WallaschofskiH. 2010. Associations of anthropometric parameters with serum TSH, prolactin, IGF-I, and testosterone levels: results of the study of health in Pomerania (SHIP). Exp Clin Endocrinol Diabetes, 118:266–273.
10.
SgarbiJA, KasamatsuTS, MatsumuraLK, MacielRM. 2010. Parity is not related to autoimmune thyroid disease in a population-based study of Japanese-Brazilians. Thyroid, 20:1151–1156.
11.
WalshJP, BremnerAP, BulsaraMK, O'LearyP, LeedmanPJ, FeddemaP, MichelangeliV. 2005. Parity and the risk of autoimmune thyroid disease: a community-based study. J Clin Endocrinol Metab, 90:5309–5312.
12.
VestergaardP, RejnmarkL, WeekeJ, HoeckHC, NielsenHK, RungbyJ, LaurbergP, MosekildeL. 2002. Smoking as a risk factor for Graves' disease, toxic nodular goiter, and autoimmune hypothyroidism. Thyroid, 12: 69–75.
13.
MassoudiMS, MeilahnEN, OrchardTJ, FoleyTPJr, KullerLH, CostantinoJP, BuhariAM. 1995. Prevalence of thyroid antibodies among healthy middle-aged women. Findings from the thyroid study in healthy women. Ann Epidemiol, 5:229–233.
14.
LaurbergP, JorgensenT, PerrildH, OvesenL, KnudsenN, Bülow PedersenI, RasmussenLB, CarleA, VejbjergP. 2006. The Danish investigation on iodine intake and thyroid disease, DanThyr: status and perspectives. Eur J Endocrinol, 155:219–228.
15.
KnudsenN, Bülow PedersenI, JorgensenT, LaurbergP, OvesenL, PerrildH. 2000. Goitre prevalence and thyroid abnormalities at ultrasonography: a comparative epidemiological study in two regions with slightly different iodine status. Clin Endocrinol (Oxf), 53:479–485.
16.
KnudsenN, Bülow PedersenI, JorgensenT, LaurbergP, OvesenL, PerrildH (2000) Comparative study of thyroid function and types of thyroid dysfunction in two areas in Denmark with slightly different iodine status. Eur J Endocrinol, 143:485–491.
17.
BjergvedL, JorgensenT, PerrildH, CarleA, CerqueiraC, KrejbjergA, LaurbergP, OvesenL, Bülow PedersenI, BankeRL, KnudsenN. 2012. Predictors of change in serum TSH after iodine fortification: an 11-year follow-up to the DanThyr study. J Clin Endocrinol Metab, 97:4022–4029.
18.
RasmussenLB, JorgensenT, PerrildH, KnudsenN, KrejbjergA, LaurbergP, Bülow PedersenI, BjergvedL, OvesenL. 2014. Mandatory iodine fortification of bread and salt increases iodine excretion in adults in Denmark—a 11-year follow-up study. Clin Nutr, 33:1033–1040.
19.
WHO UNICEF ICCIDD. 2007. Assessment of Iodine Deficiency Disorders and Monitoring Their Elimination. World Health Organization, Geneva.
20.
Bülow PedersenI, KnudsenN, JorgensenT, PerrildH, OvesenL, LaurbergP (2003) Thyroid peroxidase and thyroglobulin autoantibodies in a large survey of populations with mild and moderate iodine deficiency. Clin Endocrinol (Oxf), 58:36–42.
21.
Bülow PedersenI, KnudsenN, CarleA, VejbjergP, JorgensenT, PerrildH, OvesenL, BankeRL, LaurbergP. 2011. A cautious iodization program bringing iodine intake to a low recommended level is associated with an increase in the prevalence of thyroid autoantibodies in the population. Clin Endocrinol (Oxf), 75:120–126.
22.
VejbjergP, KnudsenN, PerrildH, LaurbergP, AndersenS, RasmussenLB, OvesenL, JorgensenT. 2009. Estimation of iodine intake from various urinary iodine measurements in population studies. Thyroid, 19:1281–1286.
23.
ZimmermannMB, AnderssonM. 2012. Assessment of iodine nutrition in populations: past, present, and future. Nutr Rev, 70:553–570.
24.
LaurbergP. 1987. Thyroxine and 3,5,3′-triiodothyronine content of thyroglobulin in thyroid needle aspirates in hyperthyroidism and hypothyroidism. J Clin Endocrinol Metab, 64:969–974.
25.
WilsonB, VanZA. 1967. The estimation of iodine in thyroidal amino acids by alkaline ashing. S Afr J Med Sci, 32:70–82.
26.
RasmussenLB, CarleA, JorgensenT, KnudsenN, LaurbergP, Bülow PedersenI, PerrildH, VejbjergP, OvesenL. 2008. Iodine intake before and after mandatory iodization in Denmark: results from the Danish Investigation of Iodine Intake and Thyroid Diseases (DanThyr) study. Br J Nutr, 100:166–173.
27.
VickersAJ, AltmanDG. 2001. Statistics notes: analysing controlled trials with baseline and follow up measurements. BMJ, 323:1123–1124.
28.
WalshJP, BremnerAP, BulsaraMK, O'LearyP, LeedmanPJ, FeddemaP, MichelangeliV. 2005. Parity and the risk of autoimmune thyroid disease: a community-based study. J Clin Endocrinol Metab, 90:5309–5312.
29.
JorgensenKT, PedersenBV, NielsenNM, JacobsenS, FrischM. 2012. Childbirths and risk of female predominant and other autoimmune diseases in a population-based Danish cohort. J Autoimmun, 38:J81–J87.
30.
FriedrichN, SchwarzS, ThonackJ, JohnU, WallaschofskiH, VolzkeH. 2008. Association between parity and autoimmune thyroiditis in a general female population. Autoimmunity, 41:174–180.
31.
GreerLG, CaseyBM, HalvorsonLM, SpongCY, McIntireDD, CunninghamFG. 2011. Antithyroid antibodies and parity: further evidence for microchimerism in autoimmune thyroid disease. Am J Obstet Gynecol, 205:471–474.
32.
CarleA, Bülow PedersenI, KnudsenN, PerrildH, OvesenL, RasmussenLB, LaurbergP. 2014. Development of autoimmune overt hypothyroidism is highly associated with live births and induced abortions but only in premenopausal women. J Clin Endocrinol Metab, 99:2241–2249.
33.
BrixTH, HansenPS, KyvikKO, HegedusL. 2009. Aggregation of thyroid autoantibodies in twins from opposite-sex pairs suggests that microchimerism may play a role in the early stages of thyroid autoimmunity. J Clin Endocrinol Metab, 94:4439–4443.
34.
StriederTG, PrummelMF, TijssenJG, EndertE, WiersingaWM. 2003. Risk factors for and prevalence of thyroid disorders in a cross-sectional study among healthy female relatives of patients with autoimmune thyroid disease. Clin Endocrinol (Oxf), 59:396–401.
35.
EffraimidisG, TijssenJG, WiersingaWM. 2009. Discontinuation of smoking increases the risk for developing thyroid peroxidase antibodies and/or thyroglobulin antibodies: a prospective study. J Clin Endocrinol Metab, 94:1324–1328.
36.
FrankP, KayCR. 1978. Incidence of thyroid disease associated with oral contraceptives. Br Med J, 2:1531.
37.
KnudsenN, Bülow PedersenI, LaurbergP, PerrildH, OvesenL, JorgensenT. 2002. Low goitre prevalence among users of oral contraceptives in a population sample of 3712 women. Clin Endocrinol (Oxf), 57:71–76.
38.
PrummelMF, StriederT, WiersingaWM. 2004. The environment and autoimmune thyroid diseases. Eur J Endocrinol, 150:605–618.
PhillipsDI, LazarusJH, ButlandBK. 1990. The influence of pregnancy and reproductive span on the occurrence of autoimmune thyroiditis. Clin Endocrinol (Oxf), 32:301–306.
41.
LaurbergP, PedersenKM, VestergaardH, SigurdssonG. 1991. High incidence of multinodular toxic goitre in the elderly population in a low iodine intake area vs. high incidence of Graves' disease in the young in a high iodine intake area: comparative surveys of thyrotoxicosis epidemiology in East-Jutland Denmark and Iceland. J Intern Med, 229:415–420.
42.
LaurbergP, CerqueiraC, OvesenL, RasmussenLB, PerrildH, AndersenS, Bülow PedersenI, CarleA. 2010. Iodine intake as a determinant of thyroid disorders in populations. Best Pract Res Clin Endocrinol Metab, 24:13–27.
43.
ZoisC, StavrouI, SvarnaE, SeferiadisK, TsatsoulisA. 2006. Natural course of autoimmune thyroiditis after elimination of iodine deficiency in northwestern Greece. Thyroid, 16:289–293.
