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.

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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.

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What are your experiences? We would love to hear more

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References

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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

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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