This study is aimed to investigate the metformin effect on the fertility of women treated with 131 I for thyroid cancer
One of the most common types of endocrine cancer, especially in young women, is thyroid cancer. More than 90% of all thyroid cancers are differentiated thyroid cancers (DTC), including papillary thyroid cancer (PTC) and follicular cancer. Papillary thyroid cancer is considered as indolent tumour as progression free survival is 10 years of 98%. As per current knowledge and basing on current literature most of the PTC are considered to be low incidence of recurrence or metastasis, however, there are more invasive/aggressive types with very specific pathological and molecular characteristics. The aggressive variants of PTC were strictly associated with higher rates of extrathyroid extension, multifocality, and nodal and distant metastasis. Thyroidectomy followed by radioactive iodine 131 (131I) therapy, in higher stages of PTC disease to ablate residual thyroid cancer or treat metastases, significantly increase survival Metformin (1,1-dimethylbiguanide) is an oral antihyperglycemic drug. Orally administered metformin is absorbed into the blood in 40-60% of the drug dose. Maximum blood levels are reached after approximately 2.5 hours for the immediate-release formulation and 7 hours for the prolonged-release tablets. It is not metabolised in the liver, however, it is excreted unchanged by the kidneys, mainly through the renal tubules. Metformin is used in patients with type 2 diabetes and prediabetes as well as in insulin resistant state and in women with polycystic ovary syndrome (PCOS). Metformin works by lowering level of glucose in the blood by lowering its production by the liver and increasing the sensitivity to insulin by muscle and fat tissue. It also has a beneficial effect on serum lipids by reducing the concentration of triglycerides, total cholesterol, LDL-cholesterol and VLDL. Additionally, this drug has also several other biological effects such as anti-inflammatory, anticancer, hepatoprotective, cardioprotective, otoprotective, radioprotective and radio-sensitising. Currently there is also a large evidential material for effectiveness of metformin therapy in re-establishing of reproductive functions and fertility in women with polycystic ovary syndrome. Having proved the metformin restore of ovulation in PCOS and has antioxidant properties there are indications that metformin can be a therapy which will helps to maintain ovary follicle number on acceptable level. At present, there are no performed studies concerned on the evaluation of the potential beneficial effect of metformin application impact on fertility parameters in the group of women treated with 131I. Therefore, the proposed study will assess the effect of metformin intervention on the indirect parameters of fertility of women treated with 131I for papillary thyroid cancer
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
160
Metformin will be used 3 times a day (3x500mg), starting in the first week with 1x1 tablet (1x500 mg for breakfast), in the second week, 2x1 tablet (500 mg for breakfast and 500 mg for dinner), from the 3rd week 3x1 tablet. (3x500mg with main meals). A gradual escalation of the dose is planned to the point of developing drug intolerance or toxicity that is unacceptable to the patient.
Patients qualified to receive 131I treatment
Department of Endocrinology, Diabetology and Internal Medicine, Medical Univeristy of Bialystok
Bialystok, Poland
Changes in AMH, Inhibin B and FSH levels due to the action of metformin
The primary endpoint will be to evaluate the effect of metformin on the difference in serum AMH, inhibin B and FSH concentration and the number of antral follicles, assessed in the study groups consisted of the women with papillary thyroid cancer, treated with 131I, comparing received results during the randomized, V3, V4, V5 and V6 visits
Time frame: 4 years
Assessment of the effect of metformin on the parameters of oxidative stress
To evaluate the metformin modulating impact on the concentrations of selected parameters of oxidative stress assessed in the study groups consisted of the women with papillary thyroid cancer, treated with 131I, comparing received results during the randomized, V3, V4, V5 and V6 visits
Time frame: 4 years
The evaluate of difference in serum concentration of selected parameters of apoptosis
To evaluate the effect of metformin on the difference in serum concentration of selected parameters of apoptosis between the study groups in women with papillary thyroid cancer, treated with 131I, comparing received results during the randomized, V3, V4, V5 and V6 visits
Time frame: 4 years
The evaluate of difference in expression in selected microRNA
To evaluate the effect of metformin on the difference of expression in selected microRNA between the study groups in women with papillary thyroid cancer, treated with 131I, between the randomized visit and V3, V4, V5 and V6 visit
Time frame: 4 years
Agnieszka Adamska, Assoc.Prof.
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