This retrospective study observed the clinical data in euthyroid and mild subclinical hypothyroidism postmenopausal women underwent MHT, compared endocrine hormone levels and metabolic status before and after MHT. In this study, there were no statistically significant differences in age, time of menopause, BMI and other baseline indexes among the three groups before medication, all participants used oral MHT with same potency of estrogen, the medication regiments among the three groups were comparable.
It had been consensus that MHT through exogenous supplementation of estrogen to reduce the level of FSH in serum, and maintain a certain E2 level to meet the needs of various organs in the body, so as to relieve menopausal symptoms[16]. In our study, the serum FSH decreased and E2 increased in all three groups comparing with the baseline, and no difference at follow-up between the three groups were noted, that is consistent with previous researches.
Previous studies had examined the effects of MHT on thyroid function in euthyroid postmenopausal women. In the study of Benencia et al[17], postmenopausal women used oral MHT showed serum TBG and tT4 increased at 3, 6 and 12 months, but within the normal range, serum TSH, fT4 and total triiodothyronine (tT3) levels did not change significantly and remained within the normal range. Ceresini et al.[18] reported serum TSH did not change significantly after 1 year estrogen therapy in euthyroid postmenopausal women. Marqusee et al.[19] revealed the administration of conjugated estrogen for 6 weeks increased serum TSH concentrations, but does not alter fT4 index values in postmenopausal women, moreover, serum TSH values remained within the normal range. For postmenopausal women with thyroid dysfunction, only a little study observed the effects caused by MHT. In a 48-week study, Arafah investigated the effects of oral MHT on thyroid function in postmenopausal women, in women with normal thyroid function, TBG and tT4 levels increased, fT4 and TSH levels did not change, in women with primary hypothyroidism in the meantime received L-T4 therapy, oral MHT produced a marked and sustained increase in TBG levels and a parallel increase in tT4 levels, however, in contrast to euthyroid women, the serum fT4 levels decreased significantly and the average serum TSH levels increased markedly, 40% patients had their L-T4 doses increased after their TSH levels had exceeded the predetermined limits set in the protocol [8, 20]. Our study found that after MHT, serum TSH increased and fT3, fT4 decreased in euthyroid women with a lower normal TSH level, serum TSH decreased and fT3, fT4 remained no change in euthyroid women with a upper normal TSH level, but all serum TSH, fT3 and fT4 levels were still within the normal range of reference values, this result is consistent with previous researches. In mild subclinical hypothyroidism postmenopausal women, serum fT3 level decreased significantly, while still within the normal range, serum TSH and fT4 showed no significant change before and after treatment. This study is the first one analyzed the effects of MHT on mild subclinical hypothyroidism postmenopausal women. The result suggested that MHT has no significant effect on thyroid function, does not lead to increased demand for thyroxine or aggravate the trend of clinical hypothyroidism for mild subclinical hypothyroidism postmenopausal women.
Consistent results from several large randomized controlled trials indicated that MHT produced significant increasing in HDL-C,TG levels, and reductions in LDL-C levels, also led to a decline in FPG levels and decreased the incidence of type 2 diabetes[21–24]. This study showed that MHT led to improvements of lipid parameters in euthyroid postmenopausal women, which is consistent with previous studies in portion of lipid indicators, while there was no significant changes of lipid parameters in mild subclinical hypothyroidism postmenopausal women before and after treatment. Possibly elevated TSH impairs the ability of MHT to improve lipid levels, further research is required. In this study, we found that MHT significantly decreased FPG, FINS and HOMA-IR in euthyroid postmenopausal women with low normal TSH range. However, there were no significant differences in between euthyroid women with upper normal TSH level or mild subclinical hypothyroidism women. Based on the present results, women with low normal TSH range showed more obvious within-group improvements in glucose and lipid metabolism after MHT.
There are several potential limitations to this study. First, the investigation was a retrospective analysis. Second, the sample size of women in group III was too small. Third, selection and recall bias existed in the recruitment of the participants. Given these limitations, further prospective studies with larger sample sizes and homogeneous hormone therapies are required.