Skip to main content
NCBI home page
Medicine logoLink to Medicine
. 2023 Jun 16;102(24):e34074. doi: 10.1097/MD.0000000000034074

Women consuming oral contraceptives containing cyproterone acetate and ethinylestradiol show a higher risk of thyroid cancer than nonusers

Pei-Hsuan Lai a, Weishan Chen b,c, Chung Y Hsu d, Jen-Hung Wang e, Dah-Ching Ding a,f,*
PMCID: PMC10270523  PMID: 37327266

Abstract

This study explored whether the risk of thyroid cancer in Asian women is associated with consumption of oral contraceptives (Diane-35). We conducted a population-based, retrospective cohort study using the Taiwan National Health Insurance Research Database. From the database, 9865 women aged 18 to 65 years who were prescribed Diane-35 between 2000 and 2012 were included in the Diane-35 group, and 39,460 women who were not prescribed Diane-35 were included in the comparison group and were frequency-matched by age and index year. Both groups were followed until 2013 to calculate the incidence of thyroid cancer. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated using Cox proportional hazard model. The median (standard deviation) follow-up duration was 7.08 (3.63) and 7.04 (3.64) years in the Diane-35 and the comparison group, respectively. The incidence of thyroid cancer was 1.80-fold higher in the Diane-35 group than in the comparison group (2.72 vs 1.51 per 10,000 person-years). The cumulative incidence of thyroid cancer was significantly higher in the Diane-35 group than in the comparison group (log-rank test, P = .03). An elevated hazard ratio of thyroid cancer was observed in the Diane-35 group than in the comparison group (HR: 1.91, 95% CI: 1.10–3.30). In subgroup analysis, patients aged 30 to 39 years showed a higher hazard ratio of developing thyroid cancer after consuming Diane-35 than those in the comparison group (HR: 5.58, 95% CI: 1.84–16.91). The study provides evidence that women aged 30 to 39 years consuming Diane-35 are at increased risk of thyroid cancer. Nevertheless, a larger population with a longer follow-up may be necessary to confirm causality.

Keywords: Diane-35, oral contraceptives, thyroid cancer

1. Introduction

Oral contraceptives (OCs) are hormone-containing products used to prevent pregnancy. Inhibition of ovulation and prevention of sperm penetration into the cervix are the main mechanisms for avoiding pregnancy.[1] Prevention of ovulation is the main mechanism of contraceptives of combined oral contraceptives.

The most common forms of oral contraceptives are synthetic female hormones – estrogen (E) and progesterone (P). This type of pill is called a combined oral contraceptive. Another form of oral contraceptives, such as minipill, contains progestin alone. Diane-35 (Bayer Weimer GmbH und Co., Weimer, Germany) is a combined form of an oral contraceptive containing 2 mg cyproterone acetate and 0.035 mg ethinylestradiol. Indications for Diane-35 include acne, seborrhea, hirsutism, polycystic ovarian syndrome, and pregnancy prevention.[2] Oral contraceptives increase the risk of breast and cervical cancers and decrease the risk of ovarian, endometrial, and colorectal cancers.[3] However, the risk of developing thyroid cancer after oral contraceptives is inconclusive.[4–6]

Estrogen may play a role in the development and progression of certain types of thyroid cancer.[7] The thyroid gland expresses estrogen receptors (ERs), specifically ERα and ERβ. These receptors allow estrogen to bind and exert its effects on thyroid cells.[7] Thyroid cancer can be broadly classified into several types, including papillary thyroid carcinoma (PTC), follicular thyroid carcinoma (FTC), medullary thyroid carcinoma, and anaplastic thyroid carcinoma. Estrogen’s role in thyroid cancer has been studied primarily in PTC and FTC, which are the most common types.[8] Estrogen can promote cell proliferation, inhibit cell death (apoptosis), and stimulate angiogenesis (formation of new blood vessels) in thyroid cancer cells.[9] These effects are mediated through estrogen receptors and various signaling pathways. Studies have suggested that estrogen may contribute to the growth and progression of thyroid cancer. Higher levels of estrogen have been associated with larger tumor size, increased lymph node metastasis, and advanced disease stage in PTC and FTC.[10] Some studies have suggested that longer exposure to estrogen over multiple menstrual cycles may increase the risk of thyroid cancer.[11] Estrogen exposure may modify the impact of ionizing radiation, a known risk factor for thyroid cancer, potentially enhancing its carcinogenic effects.[12] Further research is needed to gain a better understanding of the precise relationship between estrogen exposure and the development of thyroid cancer.

In Taiwan, the incidence of thyroid cancer increased from 8.09 to 14.5 per 1000,000 persons between 2002 and 2012.[13] In a previous study, we found that the risk of thyroid cancer (adjusted incidence rate ratio: 1.80) increased after the consumption of infertility medication (clomiphene, estrogen, and progesterone) in people in Taiwan.[14] The female gender is prone to thyroid cancer which suggests sex steroid hormones may be elaborated in the occurrence of thyroid cancer. A large pooled analysis showed a weak association between several menstrual and reproductive factors (later age at menarche, abortion, and parity) and thyroid cancer.[15] Therefore, exploring exogenous estrogen exposure may provide more information.

Diane-35 is the only combined form OC paid by National Health Insurance. Therefore, this study aimed to determine the association between Diane-35 and the risk of thyroid cancer. A population-based health insurance database was used to generate the data.

2. Materials and methods

2.1. Data source

In 1996, the Taiwanese government initiated a national program called the National Health Insurance program that aimed to improve national health and medical care in Taiwan. The medical records were stored in the National Health Insurance Research Database, which contains information on patient demographics, diagnoses, examinations, drug prescriptions, and operations from all medical care settings for > 99% of the 23 million Taiwanese individuals.

We analyzed data from the Longitudinal Health Insurance Database 2000, including all original claims data for 1 million beneficiaries randomly sampled from the registry of all beneficiaries enrolled in Taiwan’s National Health Insurance Program between January 1, 2000, and December 31, 2013. Disease diagnosis was coded using the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM). All data used in this study were anonymized before their use. Permission from the Taiwan National Health Insurance Department was required to access the raw data used in our study. The Research Ethics Committee at China Medical University and Hospital approved using NHRI-provided data for studies (institutional review board permit number: CMUH-104-REC2-115). The Research Ethics Committee at China Medical University and Hospital approved a waiver of informed consent. The study has been performed by the Declaration of Helsinki. All methods were carried out by relevant guidelines and regulations.

2.2. Study population

The case cohort comprised women administered Diane-35 (anaplastic thyroid carcinoa code G03HB) between 2000 and 2012. Diane-35 was paid by insurance with the indications of polycystic ovarian disease, hirsutism, or menstrual irregularities. We selected 4 individuals not consuming Diane-35 as the control cohort through frequency matching with the study cohort by age (in 5-years intervals) and index year. The index date of the Diane-35 users was set as the first prescription date, and that of the controls was set as a random date after enrollment. Patients aged < 18 and > 65 years, diagnosed with all cancer (ICD-9-CM code: 140-208) before the index date, and diagnosed with any cancer before or 1 year after the index date were excluded (Fig. 1).

Figure 1.

Figure 1.

Open in a new tab

Study flow chart. NHIRD = National Health Insurance Research Database.

2.3. Main outcome and covariates

The confirmation of thyroid cancer (ICD-9-CM code: 193) events was based on the registry of catastrophic illness, a sub-data set of the NHIRD. Each patient was followed until a diagnosis of thyroid cancer was confirmed, until the patient was censored for loss at follow-up, death, withdrawal from the insurance system, or to the end of the follow-up (December 31, 2013). The related comorbidities included hypertension (ICD-9-CM code 401–405), diabetes (ICD-9-CM code 250), hyperlipidemia (ICD-9-CM code 272), stroke (ICD-9-CM code 430–438), coronary heart disease (ICD-9-CM code 410–414), congestive heart failure (ICD-9-CM codes 398.91, 402.01, 402.11, 402.91, 404.01, 404.03, 404.11, 404.13, 404.91, 404.93, 425.4–425.9, and 428), chronic obstructive pulmonary disease (ICD-9-CM codes 491, 492, 493, and 496), endometriosis (ICD-9-CM code 617), and polycystic ovarian disease (PCOS, ICD-9-CM code 256.4) that occurred before the index date.

2.4. Statistical analysis

The chi-square test was used to test the difference in the distribution of categorical variables between the 2 groups. Student t test was used to assess the difference in mean age and mean follow-up time for thyroid cancer. The incidence rate was calculated as 10,000 person-years. Hazard ratios and 95% confidence intervals (CIs) were estimated using the Cox proportional hazard model. Age was included as a continuous variable in the Cox model to account for adjustment. We used the Kaplan–Meier method to plot the cumulative incidence curves and log-rank tests to examine differences between the 2 cohorts. Statistical analyses were performed using SAS version 9.4, and data were plotted using R version 4.0. Statistical significance was set at P < .05.

3. Results

A total of 49,325 subjects were included in this study; 9865 were Diane-35 users and 39,460 were Diane-35 nonusers. Table 1 presents the demographic and baseline clinical characteristics of the study population. The patients’ mean age was 33.5 ± 9.93 and 33.4 ± 10.3 years in the Diane-35 and comparison cohorts, respectively. The mean and standard difference of follow-up duration were 7.08 ± 3.63 and 7.04 ± 3.64 years for participants in the Diane-35 and comparison cohorts, respectively. The distribution of comorbidities in the Diane-35 and comparison groups was significantly different, such as hypertension (6.94% vs 5.84%), diabetes (2.97% vs 2.28%), hyperlipidemia (8.62% vs 5.94%), coronary heart disease (2.51% vs 1.82%), chronic obstructive pulmonary disease (5.26% vs 3.49%), endometriosis (12.0% vs 3.79%), and PCOS (7.73% vs 1.11%).

Table 1.

Baseline characteristics of women in Diane-35 and comparison cohorts.

Characteristics Diane-35 cohort Comparison cohort P
(n = 9865) (n = 39,460)
Age, yr
 18–29 4280 (43.4) 17120 (43.4) 1.00
 30–39 2718 (27.6) 10872 (27.6)
 40–49 2335 (23.7) 9340 (23.7)
 50–65 532 (5.39) 2128 (5.39)
Mean (SD) 33.5 (9.93) 33.4 (10.3) .40
Follow-up duration, years
 Mean (SD) 7.08 (3.63) 7.04 (3.64) .37
Comorbidity, n (%)
 Hypertension 685 (6.94) 2303 (5.84) <.0001
 Diabetes 293 (2.97) 899 (2.28) <.0001
 Hyperlipidemia 850 (8.62) 2342 (5.94) <.0001
 Stroke 23 (0.23) 102 (0.26) .65
 CAD 248 (2.51) 717 (1.82) <.0001
 CHF 52 (0.53) 183 (0.46) .41
 COPD 519 (5.26) 1376 (3.49) <.0001
 Endometriosis 1180 (12.0) 1496 (3.79) <.0001
 PCOS 763 (7.73) 439 (1.11) <.0001
Open in a new tab

CAD = coronary artery disease; CHF = congestive heart failure; COPD = chronic obstructive pulmonary disease, PCOS = polycystic ovarian disease.

Table 2 compares the incidence rates of thyroid cancer in both cohorts based on age stratification. After adjusting for age and comorbidities, the hazard ratio of thyroid cancer in participants in the Diane-35 cohort was 1.91 (95% CI = 1.10–3.30), higher than that in participants in the comparison cohort for all ages. Furthermore, for patients aged 30 to 39 years, Diane-35 users had a significantly higher hazard ratio of thyroid cancer (adjusted hazard ratios = 5.58; 95% CI = 1.84–16.91) than those not consuming Diane-35.

Table 2.

Risk of thyroid cancer in women consuming Diane-35 than those in comparison group.

Groups N Event Person-years Incidence per 10,000 person-years HR (95% CI)
Crude Adjusted*
All ages
 Comparison group 39,460 42 277,754 1.51 1 (reference) 1 (reference)
 Diane-35 user 9865 19 69,804 2.72 1.80 (1.04–3.09) 1.91 (1.10–3.30)
Age 18–29
 Comparison group 17,120 16 116,032 1.38 1 (reference) 1 (reference)
 Diane-35 user 4280 3 29,212 1.03 0.74 (0.22–2.55) 0.86 (0.25–2.96)
Age 30–39
 Comparison group 10,872 6 71,980 0.83 1 (reference) 1 (reference)
 Diane-35 user 2718 7 18,041 3.88 4.66 (1.57–13.86) 5.58 (1.84–16.91)
Age 40–49
 Comparison group 9340 18 71,418 2.52 1 (reference) 1 (reference)
 Diane-35 user 2335 9 17,916 5.02 1.99 (0.89–4.42) 2.07 (0.92–4.64)
Age 50–65
 Comparison group 2128 2 18,323 1.09 1 (reference) 1 (reference)
 Diane-35 user 532 0 4634 0.00 - -
Open in a new tab
*

Model is adjusted by age and comorbidities listed in Table 1.

As shown in Figure 2, the cumulative incidence of thyroid cancer was significantly higher in the Diane-35 cohort than in the comparison cohort (log-rank test, P = .03).

Figure 2.

Figure 2.

Open in a new tab

Kaplan–Meier curves depict the cumulative incidence of thyroid cancer in the Diane-35 (dashed line) and comparison (solid line) cohorts matched by age and comorbidities.

4. Discussion

The results of the present study showed that the incidence of thyroid cancer was 1.80-fold higher in Diane-35 users than in women in the comparison group. An elevated risk of thyroid cancer was observed. Although only 19 thyroid cancer cases developed in Diane-35 users, the study model was valid. In subgroup analysis, the 30 to 39 years age group showed a higher risk of developing thyroid cancer after consuming Diane-35 than the comparison group.

The NIH-AARP Diet and Health Study found OC used for more than 10 years were inversely associated with the risk of thyroid cancer than never used.[16] Menopausal hormone therapy (MHT) was associated with an increased thyroid cancer risk compared with never users.[16] The previous meta-analysis included 6 cohort studies and 3 case-control studies that found no association between MHT and thyroid cancer risk.[17] MHT with E + P was associated with a decreased risk of thyroid cancer in a nationwide Swedish population-based cohort study.[18] Ever use or estrogen-only MHT among aged ≥ 45 years women were not associated with thyroid cancer.[19] In our study, a small population used Diane-35 as MHT. The MHT users (50–65 years) were not associated with thyroid cancer risk. Taken together, conflict data were noted regarding the association between MHT and thyroid cancer.

A prospective cohort study also showed that OC users had a higher incidence rate of thyroid cancer than nonusers.[20] OC use was not associated with the risk of thyroid cancer in a prospective cohort study.[19] The previous meta-analysis showed that oral contraceptives failed to alter the risk of thyroid cancer.[6] A systematic review also failed to find a correlation between OC and thyroid cancer risk.[21] Another matched case-control study (292 pairs) also showed that OC is not associated with the risk of thyroid cancer.[22] Conversely, a meta-analysis of studies suggested a protective effect of prolonged oral contraceptives on developing thyroid cancer.[4] A population-based, case-control study showed that OC use was associated with a reduced risk of thyroid cancer.[15] In a subgroup analysis of our study, patients aged 30 to 39 years showed a higher risk of developing thyroid cancer after consuming Diane-35 than those in the comparison group. Taken together, conflict data were noted regarding the association between OC and thyroid cancer.

A Danish nationwide cohort showed progesterone was associated with an increased risk of thyroid cancer.[23] The Taiwanese population cohort also found that the risk of thyroid cancer (adjusted incidence rate ratio: 1.80) increased after the consumption of infertility medication (clomiphene, estrogen, and progesterone) in women.[14] Basic research showed progesterone influences thyroid function and growth by upregulating related genes in thyroid cells.[24] The previous research also found a common expression of progesterone receptor (PR) in thyroid tumor tissue.[25] Another study showed that PR status did not affect the outcome of thyroid cancer.[26] In our study, Diane-35 contained cyproterone acetate might affect the risk of thyroid cancer. Taken together, progesterone might be associated with thyroid cancer on the findings from epidemiological and basic research.

Regarding the duration of OC use, Wu and Zhu reported a significant inverse association between the longest and shortest duration of OC use and the risk of thyroid cancer. They also observed a linear relationship between the duration of OC use and thyroid cancer risk in a dose-response analysis.[27] Another study showed that OC use for 10 to 19 years decreased the risk of thyroid cancer.[28] In contrast, some studies failed to identify a trend for the duration of OC use.[5,15] Taken together, the longer the use of OC, the lower the risk of thyroid cancer.

OC use-thyroid cancer relationship is complex, and comparing studies is difficult because it depends upon the types of OCs used, the recency of use, and whether one is evaluating pre- or post-menopausal cancer risk.

In the present study, the distribution of PCOS in the 2 cohorts was significantly different. Few studies have attempted to identify cancer risk in patients with PCOS. A population-based cohort study reported that thyroid cancer risk was not affected by the presence of PCOS.[29] Nevertheless, PCOS tends to associate with an increased prevalence of autoimmune thyroid disease.[30] However, the relationship between chronic autoimmune thyroiditis and thyroid epithelial cancer remains controversial.[31] Therefore, the potential correlation between PCOS and thyroid cancer risk warrants further investigation. Moreover, in the present study, the obscure influence of the higher proportion of patients with PCOS in the Diane-35 user group should be interpreted carefully.

In our study, the proportions of diabetes, hypertension, and hyperlipidemia among women in the Diane-35 cohort were larger than those in the comparison cohort. OCs are reported that may be related to hypertension,[32] diabetes,[33] and hyperlipidemia.[34] A larger portion of PCOS was also noted in the Diane-35 cohort, which may be associated with hyperlipidemia.[35] Nevertheless, in our analysis, these comorbidities were adjusted, and found the association between Diane-35 use and thyroid cancer.

The biological plausibility of estrogen’s role in thyroid cancer stems from the fact that thyroid cells have estrogen receptors, which enable them to respond to estrogen signaling.[36] Estrogen can affect thyroid cell growth, proliferation, and survival through these receptors.[7] Moreover, estrogen metabolism enzymes, such as aromatase, are present in thyroid tissues, suggesting local estrogen production and modulation.[37]

Age is an important factor in the interaction between estrogen and thyroid cancer risk.[16] The incidence of thyroid cancer is higher in women than men, and this gender disparity is most prominent during the reproductive years. The age-specific incidence rates of thyroid cancer tend to peak in women in their 40s and 50s, which is a time of hormonal fluctuations and declining ovarian function.[38] However, in our study, women aged 30 to 39 taking Diane-35 had a higher risk of thyroid cancer but not other age groups compared with non-Diane-35 users (Table 2). This might be caused by the influence of adding OC hormone (exogeneous hormone) on the oncogenesis of the thyroid gland in women aged 30 to 39. Nevertheless, this phenomenon needs further exploration.

The present study has several strengths. First, the database covered 1 million people sampled from the entire population (23 million) in Taiwan. Second, all medical records were accurately recorded using the National Health Insurance Research Database. Third, an age-matched method was applied to the comparison cohort, which was the primary confounding factor. Fourth, the effect of only 1 OC, which does not represent all forms of OC, was explored in this study. Finally, the cohort used in this study was the most suitable model for exploring the association between OC and thyroid cancer.

However, this study has several limitations. First, the database covers only 13 years, with a short follow-up duration (7.08 and 7.04 years in the Diane and comparison cohorts, respectively). Second, other confounding factors for thyroid cancer, such as lifestyle and behavioral factors (e.g., diet or exercise), were not recorded in the database. Third, comorbidities of thyroid cancer were identified using ICD-9-CM codes that may not always be precise. Therefore, these results should be interpreted cautiously due to their moderate statistical significance.

5. Conclusions

This nationwide, population-based, retrospective cohort study showed that consuming Diane-35 was associated with an increased risk of thyroid cancer. However, a larger population with a longer follow-up may be necessary to determine causality. Healthcare workers should counsel women who wish to use Diane-35 regarding their long-term potential health impact on the incidence of thyroid cancer.

Author contributions

Conceptualization: Dah-Ching Ding.

Data curation: Weishan Chen, Dah-Ching Ding.

Formal analysis: Weishan Chen, Dah-Ching Ding.

Funding acquisition: Weishan Chen.

Methodology: Pei-Hsuan Lai.

Software: Chung Y. Hsu.

Supervision: Chung Y. Hsu, Jen-Hung Wang.

Writing – original draft: Pei-Hsuan Lai, Weishan Chen, Dah-Ching Ding.

Writing – review & editing: Dah-Ching Ding.

Abbreviations:

CI
confidence intervals
E
estrogen
FTC
follicular thyroid carcinoma
ICD-9-CM
International Classification of Diseases, Ninth Revision, Clinical Modification
MHT
menopausal hormone therapy
OCs
oral contraceptives
P
progesterone
PCOS
polycystic ovarian disease
PR
progesterone receptor
PTC
papillary thyroid carcinoma

Oral contraceptives and thyroid cancer risk.

This study was partly supported by the China Medical University Hospital (DMR-110-105) and the Tseng-Lien Lin Foundation, Taichung, Taiwan.

The Research Ethics Committee at China Medical University and Hospital approved the use of NHRI-provided data for studies (institutional review board permit number: CMUH-104-REC2-115).

Informed consent was waived due to low risk of patient safety and approved by the committee.

The authors have no conflicts of interest to disclose.

The datasets generated during and/or analyzed during the current study are not publicly available, but are available from the corresponding author on reasonable request.

How to cite this article: Lai P-H, Chen W, Hsu CY, Wang J-H, Ding D-C. Women consuming oral contraceptives containing cyproterone acetate and ethinylestradiol show a higher risk of thyroid cancer than nonusers. Medicine 2023;102:24(e34074).

Contributor Information

Pei-Hsuan Lai, Email: pdeenbnbyy@gmail.com.

Weishan Chen, Email: sandy8121985@gmail.com.

Chung Y. Hsu, Email: hsucy63141@gmail.com.

Jen-Hung Wang, Email: jenhungwang2011@gmail.com.

References

  • [1].Wentzensen N, de Gonzalez AB. The Pill’s gestation: from birth control to cancer prevention. Lancet Oncol. 2015;16:1004–6. [DOI] [PubMed] [Google Scholar]
  • [2].Feng W, Jia YY, Zhang DY, et al. Management of polycystic ovarian syndrome with Diane-35 or Diane-35 plus metformin. Gynecol Endocrinol. 2016;32:147–50. [DOI] [PubMed] [Google Scholar]
  • [3].National Cancer Institute. Oral Contraceptives and Cancer Risk. National Cancer Institute; 2018. Available at: https://www.cancer.gov/about-cancer/causes-prevention/risk/hormones/oral-contraceptives-fact-sheet. [Google Scholar]
  • [4].Mannathazhathu AS, George PS, Sudhakaran S, et al. Reproductive factors and thyroid cancer risk: meta-analysis. Head Neck. 2019;41:4199–208. [DOI] [PubMed] [Google Scholar]
  • [5].Sakoda LC, Horn-Ross PL. Reproductive and menstrual history and papillary thyroid cancer risk: the San Francisco Bay Area thyroid cancer study. Cancer Epidemiol Biomarkers Prev. 2002;11:51–7. [PubMed] [Google Scholar]
  • [6].Cao Y, Wang Z, Gu J, et al. Reproductive factors but not hormonal factors associated with thyroid cancer risk: a systematic review and meta-analysis. Biomed Res Int. 2015;2015:103515. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [7].Liu J, Xu T, Ma L, et al. Signal pathway of estrogen and estrogen receptor in the development of thyroid cancer. Front Oncol. 2021;11:593479. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [8].Eldien MMS, Abdou AG, Rageh T, et al. Immunohistochemical expression of ER-α and PR in papillary thyroid carcinoma. Ecancermedicalscience. 2017;11:748. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [9].Chimento A, De Luca A, Avena P, et al. Estrogen receptors-mediated apoptosis in hormone-dependent cancers. Int J Mol Sci. 2022;23:1242. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [10].Denaro N, Romanò R, Alfieri S, et al. The tumor microenvironment and the estrogen loop in thyroid cancer. Cancers. 2023;15:2458. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [11].Moleti M, Sturniolo G, Di Mauro M, et al. Female reproductive factors and differentiated thyroid cancer. Front Endocrinol. 2017;8:111. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [12].Bogović Crnčić T, Ilić Tomaš M, Girotto N, et al. Risk factors for thyroid cancer: what do we know so far? Acta Clin Croat. 2020;59:66–72. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [13].Chiang CJ, Lo WC, Yang YW, et al. Incidence and survival of adult cancer patients in Taiwan, 2002-2012. J Formos Med Assoc. 2016;115:1076–88. [DOI] [PubMed] [Google Scholar]
  • [14].Ding DC, Chen W, Wang JH, et al. Thyroid cancer risk in women with infertility and association with fertility medications in Taiwan: infertility and thyroid cancer. Cancer. 2019;99:1324. [DOI] [PubMed] [Google Scholar]
  • [15].Xhaard C, Rubino C, Cléro E, et al. Menstrual and reproductive factors in the risk of differentiated thyroid carcinoma in young women in France: a population-based case-control study. Am J Epidemiol. 2014;180:1007–17. [DOI] [PubMed] [Google Scholar]
  • [16].Schonfeld SJ, Ron E, Kitahara CM, et al. Hormonal and reproductive factors and risk of postmenopausal thyroid cancer in the NIH-AARP diet and health study. Cancer Epidemiol. 2011;35:e85–90. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [17].Wang P, Lv L, Qi F, et al. Increased risk of papillary thyroid cancer related to hormonal factors in women. Tumour Biol. 2015;36:5127–32. [DOI] [PubMed] [Google Scholar]
  • [18].Simin J, Tamimi R, Lagergren J, et al. Menopausal hormone therapy and cancer risk: an overestimated risk? Eur J Cancer. 2017;84:60–8. [DOI] [PubMed] [Google Scholar]
  • [19].Horn-Ross PL, Canchola AJ, Ma H, et al. Hormonal factors and the risk of papillary thyroid cancer in the California Teachers Study cohort. Cancer Epidemiol Biomarkers Prev. 2011;20:1751–9. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [20].Sungwalee W, Vatanasapt P, Kamsa-ard S, et al. Reproductive risk factors for thyroid cancer: a prospective cohort study in Khon Kaen, Thailand. Asian Pac J Cancer Prev. 2013;14:5153–5. [DOI] [PubMed] [Google Scholar]
  • [21].Peterson E, De P, Nuttall R. BMI, diet and female reproductive factors as risks for thyroid cancer: a systematic review. PLoS One. 2012;7:e29177. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [22].Mack WJ, Preston-Martin S, Bernstein L, et al. Reproductive and hormonal risk factors for thyroid cancer in Los Angeles County females. Cancer Epidemiol Biomarkers Prev. 1999;8:991–7. [PubMed] [Google Scholar]
  • [23].Lindquist S, Kjær SK, Albieri V, et al. Fertility drugs and incidence of thyroid cancer in a Danish nationwide cohort of 146 024 infertile women. Hum Reprod. 2022;37:838–47. [DOI] [PubMed] [Google Scholar]
  • [24].Bertoni APS, Brum IS, Hillebrand AC, et al. Progesterone upregulates gene expression in normal human thyroid follicular cells. Int J Endocrinol. 2015;2015:864852. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [25].Sturniolo G, Zafon C, Moleti M, et al. Immunohistochemical expression of estrogen receptor-α and progesterone receptor in patients with papillary thyroid cancer. Eur Thyroid J. 2016;5:224–30. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [26].Hershman JM. Estrogen and progesterone receptors in papillary thyroid cancers do not affect outcome. Clin Thyroidol. 2015;27:155–7. [Google Scholar]
  • [27].Wu L, Zhu J. Linear reduction in thyroid cancer risk by oral contraceptive use: a dose-response meta-analysis of prospective cohort studies. Hum Reprod. 2015;30:2234–40. [DOI] [PubMed] [Google Scholar]
  • [28].Cordina-Duverger E, Leux C, Neri M, et al. Hormonal and reproductive risk factors of papillary thyroid cancer: a population-based case-control study in France. Cancer Epidemiol. 2017;48:78–84. [DOI] [PubMed] [Google Scholar]
  • [29].Yin W, Falconer H, Yin L, et al. Association between polycystic ovary syndrome and cancer risk. JAMA Oncol. 2019;5:106–7. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [30].Romitti M, Fabris VC, Ziegelmann PK, et al. Association between PCOS and autoimmune thyroid disease: a systematic review and meta-analysis. Endocr Connect. 2018;7:1158–67. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [31].Kebebew E, Treseler PA, Ituarte PH, et al. Coexisting chronic lymphocytic thyroiditis and papillary thyroid cancer revisited. World J Surg. 2001;25:632–7. [DOI] [PubMed] [Google Scholar]
  • [32].Afshari M, Alizadeh-Navaei R, Moosazadeh M. Oral contraceptives and hypertension in women: results of the enrolment phase of Tabari Cohort Study. BMC Womens Health. 2021;21:224. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [33].Kjos SL, Peters RK, Xiang A, et al. Contraception and the risk of type 2 diabetes mellitus in Latina women with prior gestational diabetes mellitus. JAMA. 1998;280:533–8. [DOI] [PubMed] [Google Scholar]
  • [34].Guedes JVM, Nunes NR, Ferreira LGR, et al. Evaluation of lipid profile, high-sensitivity C-reactive protein and D-dimer in users of oral contraceptives of different types. J Bras Patol Med Lab. 2018;54:14–20. [Google Scholar]
  • [35].Kim JJ, Choi YM. Dyslipidemia in women with polycystic ovary syndrome. Obstet Gynecol Sci. 2013;56:137–42. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [36].Derwahl M, Nicula D. Estrogen and its role in thyroid cancer. Endocr Relat Cancer. 2014;21:T273–83. [DOI] [PubMed] [Google Scholar]
  • [37].Marina D, Rasmussen AK, Buch-Larsen K, et al. Influence of the anti-oestrogens tamoxifen and letrozole on thyroid function in women with early and advanced breast cancer: a systematic review. Cancer Med. 2023;12:967–82. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [38].Du L, Zhao Z, Zheng R, et al. Epidemiology of thyroid cancer: incidence and mortality in China, 2015. Front Oncol. 2020;10:1702. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Medicine are provided here courtesy of Wolters Kluwer Health

RESOURCES