According to the results of the present study amongst all the evaluated hormones, only the mean serum level of DHEA-S in patients with RAS was significantly lower than the control group (p value = 0.002). In addition to DHEA-S, the mean serum level of testosterone was lower in the evaluation group although this difference was not significant (p value = 0.057).
Considering the effect of age on the mean serum level of sex hormones, our results revealed that only DHEA-S mean serum level was decreased by increase in the age of participants in patients with RAS (p value = 0.018).
The number of participants with abnormal range of testosterone and progesterone serum level was significantly more in patients with RAS (p value < 0.0001) (p value = 0.037).
Previous studies have shown some relationships between steroid concentration reduction and some autoimmune diseases including rheumatoid arthritis and systemic lupus erythematosus . Some similar studies reported androgen deficiency (DHT, DHEA-S, etc.) in patients with sjogren syndrom [12, 13], rheumatoid arthritis , and systemic lupus erythematosus [15, 16]. In addition, Forsblad-d’ Elia et al. prescribed 50mg oral DHEA daily for women with sjogren syndrome; they reported dry mouth symptom improvement . Taylor et al. concluded that acute stress can elevate the serum levels of DHEA-S as cortisol does . Anete Rejane et al. in an evaluation reported no significant difference in the salivary level of DHEA-S between patients with RAS and healthy controls . This result was confirmed for oral lichen planus patients in another study .
In the present study, the DHEA-S serum level was significantly lower in patients with RAS in comparison to the controls. Also in the RAS group, DHEA-S serum level was decreased by aging. This is noticeable since all the participants were premenopausal and other evaluated hormones did not show significant age related changes. DHEA-S is a precursor for androgens and estrogen. This steroid which is abundant in the human body is secreted by the adrenal cortex, CNS and gonads. The prohormones DHEA, DHEA-S which can be produced in the peripheral tissue play an important role in women’s health . IL-2 (Th1 secretion) increment and IL-6 and IL-10 reduction are the most prominent effects of this steroid. A fall in DHEA-S concentration can play an important role in the pathogenesis of some immunologic diseases .
Other previous evaluations assessed the menstrual cycle and its hormonal changes in patients with RAS. Some studies reported more frequent RAS lesions in the luteal phase in which progesterone increment plays an important role .
In accordance to what they assumed, the results of this study showed more abnormality in the progesterone and testosterone level of patients with RAS in comparison with healthy controls.
Some other evaluations did not reveal any relationship between the premenstrual phase and RAS. However, low level of progesterone has been reported in patients with mild and severe RAS [22–24]. Corpus luteam secretes progesterone during the second half of the menstrual cycle. This hormone is at its peak in the third week of menstrual cycle . Any abnormality in this hormone’s serum level can affect the immunologic function. Some studies reported more prevalent occurrence of RAS in the luteal phase ; they did not measure the serum level of this hormone. They just assessed the time association of RAS and menstrual cycle. However, in other studies decrease in the serum level of progesterone has been associated with more RAS [22–24]. Evaluating the serum level of progesterone in different phases of the menstrual cycle can reveal the exact role of progesterone changes and incidence of RAS.
There are some controversies about the role of testosterone in patients with auto-immune diseases. According to the literature testosterone has controversial effects on the systemic lupus erythematosus (SLE) complications in a different phase of disease . Also, another evaluation did not show noticeable SLE symptoms improvement by testosterone prescription . In the literature, there are some reports about the protective role of testosterone in SLE and Rheumatoid arthritis and Multiple sclerosis patients [28, 29]. In the present study, the mean serum level of testosterone in the healthy control group was more than patients with RAS; however, it was not significant (p value = 0.057). Increasing the sample size may reveal this difference more precisely. Testosterone is primarily secreted by the gonads and adrenal cortex in both sexes. Also, testosterone is synthesized from cholesterol in the brain (neurosteroid) . The proportion of its secretion changes by aging, in the fourth decade of a woman’s life, it is in half of its secretion amount . Testosterone can inhibit the effect of cyclooxygenase pathway of arachidonic acid metabolism by prostaglandin secretion inhibition. Testosterone reduction can decrease the regulatory T cells expansion, which is important in controlling auto reactive T cells and B cells expression .
Since the menopausal condition has a major effect on the level of sex hormones in this study we considered the similar non-menopause condition of all participants of both evaluated groups. The mean serum levels of FSH, LH, Prolactin, Testosterone, Estradiol and DHT have not shown any significant change by increasing the age of participants. However, DHEA-S has decreased in non-menopause participants of patients with RAS. Considering the decreasing effect of age on this hormone, in the control group, progesterone increased by aging which is challenging.
Evaluating a larger sample size of patients with RAS and assessing their sex hormones in different parts of the menstrual phase and even in postmenopausal women is recommended for future researches. Assessing these hormonal changes in males is also suggested. Revealing the effect of these hormones can introduce new methods of RAS prevention or treatment.