Hashimoto’s and polycystic ovary syndrome (PCOS)

What’s the connection?

Hashimoto’s and PCOS are connected by more than one molecular mechanism and they share certain genetic components. As they have not been extensively studied together, not much is known how their combination can impact our overall health. One condition might trigger the other, and besides genes, can be triggered by the environment. It would be interesting to know more about how or why do Hashimoto’s and PCOS co-develop, and what can we do to prevent it.

What are your experiences? We would love to hear from you

Thyroid disorders may cause irregular menstrual cycles, problems with ovulation and fertility issues (1–3).

PCOS affects up to 12 in 100 females of reproductive age (4- 7). It is characterised by irregular menstrual cycles, either multiple ovulations in one cycle or no ovulation at all, hyperandrogenism [excessive levels of testosterone] and insulin resistance (6, 8, 9). PCOS can be very different from person to person, and can also cause different grade of metabolic or menstrual cycle irregularities (10, 11).

What’s the connection?

High levels of anti-TPO or anti-Tg antibodies, a hallmark of an autoimmune thyroid condition, are found in 1 in 3 of PCOS patients (12). If a person has either Hashimoto’s or PCOS, the chance to be diagnosed with the second condition increases up to ten fold (12, 13).

Five most commonly mutated genes or molecules in Hashimoto’s and PCOS

Hashimoto’s is the most common autoimmune disorder in adults, causing a wide range of health complications (14). It is, similar to PCOS, caused by mutations in a specific set of genes (15- 19). Several of these genes are common for both Hashimoto’s and PCOS: fibrillin 3 gene (FBN3), vitamin D receptor gene (VDR) (20- 22), TGFβ (23, 24), gonadotropin-releasing hormone receptor (GnRHR) (25) and CYP1B1 (26).

Some of these molecules regulate each other, like FBN3, which regulates TGFβ (27, 28), a molecule important for many bodily processes, including regulation of the immune response (28- 31). Low levels of TGFβ are found in both Hashimoto’s and PCOS, making it hard for our body to naturally control own immune system (23, 24, 28).

Gonadotropin-releasing hormone receptor (GnRHR) is regulating how much of luteinizing hormone (LH) and follicle stimulating hormone (FSH) our body produces. It also regulates insulin balance and its function depends on TSH levels (25).

CYP1B1 is an enzyme that metabolizes estrogens, regulates thyroxine (T4), free triiodothyronine (fT3), and free T4 (fT4) levels in the body (26).

Vitamin D deficiency and high estrogen-to-progesterone ratio is often found in PCOS, and can trigger or exacerbate autoimmune response (32, 33). To have an effect on different cells and tissues in our body, vitamin D needs a functional vitamin D receptor (VDR), and a non-functional VDR is making people more likelly to develop Hashimoto’s (34, 35).

Vitamin D supplementation is supposed to improve menstrual cycle and metabolic disturbances in women with PCOS (36), but this will probably help only people who have a functional vitamin D receptor.

The thymus connection

The connection between the viscious cycle of Hashimoto’s and PCOS goes beyond genes, and it might be caused by changes in the function of the entire organ, just like it is the case with thymus.

Thymus is an organ involved in regulating and preventing autoimmune response, and it does so even before our birth (14, 37, 38). High estrogen exposure before birth prevents the activity of thymus, and in many cases triggers development of autoimmune diseases (39- 41).

The role of sex hormones

Autoimmune disease problems start when sex hormone levels rise in our body for the first time, during puberty, and it continues until the end of our lives (42).

Increased estrogen-to-progesterone ratio, as seen in PCOS causes an autoimmune response, and a rise in anti-TPO and anti-Tg antibody levels (42- 44). Transient and reversible changes in the level of autoimmune response and antibody levels even happen in non-PCOS people during distinct phases of menstrual cycle (such as ovulation; 45). However, in the case of a high and a prolonged estrogen exposure, as is the case with PCOS, the chance of developing an autoimmune disease increases significantly (12, 44).

Common health issues in Hashimoto’s and PCOS

Hashimoto’s and PCOS go beyond it’s already complex hormone and autoimmune issues. Some of the shared health issues are: higher body mass index (BMI, 46) as well as changes in glucose and lipid metabolism: an increase in LDL-cholesterol and triglycerides; and a decrease in HDL-cholesterol (47, 48), insulin resistance and a higher chance of developing type 2 diabetes (8, 49).

What can help?

Metformin, a diabetes medicine that helps control blood sugar levels is frequently prescribed to patients with PCOS. One study has shown that a six month metformin treatment in PCOS and Hashimoto’s patients normalized TSH blood values, but it did not do much for fT3 and fT4 (50). More research is needed, but perhaps it can be a valid treatment strategy for some of us.

High estrogen levels seem to be the main culprit for development of Hashimoto’s thyroiditis in people diagnosed with PCOS.

What can you do to improve your health?

You might want to avoid estrogen rich foods (soy or flax seeds).

When at your doctor’s office, ask your doctor if it makes sense to check your vitamin D, estrogen, progesterone and SBGH blood serum levels. Perhaps this will give both of you an indication if there is an estrogen-driven cause to your Hashimoto’s, and might help with finding better treatment strategies.


What are your experiences? We would love to hear more

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1. Dittrich R, et al. Thyroid hormone receptors and reproduction, 2011

2. Krassas GE, et al. Thyroid function and human reproductive health, 2010

3. Unuane D, et al. Endocrine disorders and female fertility, 2011

4. Knochenhauer ES, et al. Prevalence of the polycystic ovary syndrome in unselected black and white women of the southeastern United States: a prospective study,1998

5. Diamanti-Kandarakis E, et al. A survey of the polycystic ovary syndrome in the Greek island of Lesbos: hormonal and metabolic profile, 1999

6. Rotterdam ESHRE/ASRM-Sponsored PCOS consensus workshop group. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS), 2004

7. March WA, et al. The prevalence of polycystic ovary syndrome in a community sample assessed under contrasting diagnostic criteria, 2010

8. Dunaif A. Insulin resistance and the polycystic ovary syndrome: mechanism and implications for pathogenesis, 1997

9. Wehr E, et al. Subcutaneous adipose tissue topography and metabolic disturbances in polycystic ovary syndrome, 2009

10. Carmina E et al. Diagnosis, phenotype, and prevalence of polycystic ovary syndrome, 2006

11. Adams J, et al. Prevalence of polycystic ovaries in women with anovulation and idiopathic hirsutism, 1986

12. Janssen OE, et al. High prevalence of autoimmune thyroiditis in patients with polycystic ovary syndrome,2004

13. Ganie MA, et al. High prevalence of polycystic ovary syndrome characteristics in girls with euthyroid chronic lymphocytic thyroiditis: a case-control study, 2010

14. Hollowell JG, et al. Serum TSH, T4, and thyroid antibodies in the United States population (1988 to 1994): National Health and Nutrition Examination Survey (NHANES III), 2002

15. Dittmar M, et al. Increased familial clustering of autoimmune thyroid diseases, 2011

16. Hansen PS, et al. The relative importance of genetic and environmental effects for the early stages of thyroid autoimmunity: a study of healthy Danish twins, 2006

17. Kosova G, et al. Genetics of the polycystic ovary syndrome, 2013

18. Legro RS, et al. Evidence for a genetic basis for hyperandrogenemia in polycystic ovary syndrome,1998

19. Ehrmann DA, et al. Effects of race and family history of type 2 diabetes on metabolic status of women with polycystic ovary syndrome, 2005

20. Wehr E, et al. Association of FTO gene with hyperandrogenemia and metabolic parameters in women with polycystic ovary syndrome, 2010

21. Wojciechowski P, et al. Impact of FTO genotypes on BMI and weight in polycystic ovary syndrome: a systematic review and meta-analysis, 2012

22. Mahmoudi T. Genetic variation in the vitamin D receptor and polycystic ovary syndrome risk, 2009

23. Raja-Khan N, et al. A variant in the fibrillin-3 gene is associated with TFG-b and inhibin B levels in women with polycystic ovary syndrome, 2010

24. Akinci B, et al. Hashimoto’s thyroiditis, but not treatment of hypothyroidism, is associated with altered TGF-b1 levels, 2008

25 Li Q, et al. Common genetic variation in the 30-untranslated region of gonadotropin-releasing hormone receptor regulates gene expression in cells and is associated with thyroid function, insulin secretion as well as insulin sensitivity in polycystic ovary syndrome patients, 2011

26 Zou S, et al. Common genetic variation in CYP1B1 is associated with concentrations of T4, FT3 and fT4 in the sera of polycystic ovary syndrome patients, 2013

27. Charbonneau NL, et al. Fine tuning of growth factor signals depends on fibrillin microfibril networks. Birth Defects Research. Part C, 2004

28. Raja-Khan N, et al. The role of TGF-b in polycystic ovary syndrome, 2014

29. Shi Y et al. Mechanisms of TGF-b signaling from cell membrane to the nucleus, 2003

30. Kaartinen V et al. Fibrillin controls TGF-b activation, 2003

31. Govinden R et al. Genealogy, expression, and cellular function of transforming growth factor-b, 2003

32. Petŕıkova J et al. Ovarian failure and polycystic ovary syndrome, 2012

33. Szodoray P, et al. The complex role of vitamin D in autoimmune diseases, 2008

34. Stefanić M, et al. Association of vitamin D receptor gene 30-variants with Hashimoto’s thyroiditis in the Croatian population,2008

35. Kivity S, et al. Vitamin D and autoimmune thyroid diseases, 2011

36. Lerchbaum E, et al. Vitamin D and fertility: a systematic review, 2012

37. Weetman AP. Immunity, thyroid function and pregnancy: molecular mechanisms, 2010

38. Sakaguchi S, et al. Regulatory T cells and immune tolerance, 2008

39. Palmer JR, et al. Infertility among women exposed prenatally to diethylstilbestrol, 2001

40. West LJ. Defining critical windows in the development of the human immune system, 2002

41. Noller KL, et al. Increased occurrence of autoimmune disease among women exposed in utero to diethylstilbestrol, 1998

42. Quintero OL, et al. Autoimmune disease and gender: plausible mechanism for the female predominance of autoimmunity, 2011

43. Arduc et al. High prevalence of Hashimoto’s thyroiditis in patients with polycystic ovary syndrome: does the imbalance between estradiol and progesterone play a role? 2015

44. Petŕıkova J, et al. Polycystic ovary syndrome and autoimmunity, 2010

45. Hughes GC. Progesterone and autoimmune disease, 2012

46. Strowitzki T, et al. The degree of cycle irregularity correlates with the grade of endocrine and metabolic disorders in PCOS patients, 2010

47. Åsvold BO, et al. The association between TSH within reference range and serum lipid concentrations in a population-based study. The HUNT study, 2007

48. Park HT, et al. Thyroid stimulating hormone is associated with metabolic syndrome in euthyroid postmenopausal women, 2009

49. Cobin RH. Cardiovascular and metabolic risks associated with PCOS, 2013

50. Taghavi SM, et al. Metformin decreases thyrotropin in overweight women with polycystic ovarian syndrome and hypothyroidism, 2011