Evaluation the Serum Level of Sex Hormones in Patients With Trigeminal Neuralgia

Background and Aim: In this study FSH, LH, Testosterone, Estrogen, Progesterone serum levels in women affected by trigeminal neuralgia have been evaluated. Materials and Methods: This study is a cross sectional study during 2017-2018 in which FSH, LH, Testosterone, Estrogen, Progesterone serum levels in women affected by trigeminal neuralgia, who had referred to Emam Reza clinic and Oral and Maxillofacial Disease Department of Shiraz Dental Faculty, have been evaluated. Twenty-six women with trigeminal neuralgia were recruited in trigeminal neuralgia(TN) group and 26 healthy women whom their age were matched with TN group were enrolled in the healthy control group. Data was analyzed by SPSS version 18. Results: Sex hormone serum level was not significantly different between patients with TN and healthy control group (P value ≥0.05). In spite of this finding, the serum level of FSH in non menopausal (P value=0.002) participants and progesterone in menopausal (P value=0.016) participants of TN and healthy control group, were significantly different. The serum level for both of these hormones were higher in patients with TN. In contrast to healthy control group, the sex hormone profiles of patients with TN, except LH did not follow the natural pattern changes based on menopausal status. Conclusion: In spite of no significant differences in sex hormonal profile of patients with TN and healthy controls, some hormonal disturbance in FSH and progesterone have been detected in TN patients in comparison between non-menopause and menopausal sex hormones profile.


Introduction
Trigeminal neuralgia is a neuropathic pain, causing sudden, brief, stabbing and recurring pain, limited to a small region of the face [1] . Trigeminal neuralgia onset is usually middle or old age, but it also affects young adults and children. Trigeminal neuralgia can reoccur and lasts for few seconds. The attack might begin with stimulation of trigger zone, located within the trigeminal nerve pathway [2]. Trigeminal neuralgia is a neuropathic pain with different etiologies, causing demyelization in trigeminal zone. Neurovascular compression, multiple sclerosis, tumor, and cysts, diabetes mellitus are the most popular causes [3]. In some studies, neuropathic and neurotropic role were described for sexual hormones, even the effect of hormones on the quality and rate of nerve conduction reported. These studies showed a higher incidence of peripheral neuropathy in menopausal women [4]. Peripheral sensory and autonomic neurons express estrogen receptors [5]. The nerve transmission speed is dependent on velocity and latency (the duration between applying a stimulation and wave form record on nerve conduction study). On the other hand, the degree of myelination can significantly affect velocity and latency in nerve conduction studies [6]. A study showed that sexual hormone replacement therapy were affective on faster velocity and shorter latency, an indication for possible association between sexual hormones and nerve myelination [7]. Another study investigated whether Estrogen(E2) has a proper recovery effect on nerve injury in mice. They reported that local injection of E2 can induce greater nerve conduction velocity and vascularity [8]. In a study by Akanksha Singh explored the relationship between estrogen serum level and progesterone and -peripheral motor nerve neuropathy in postmenopausal women by motor nerve conduction velocity. Their findings reported lower level of serum estrogen in postmenopausal women with peripheral neuropathy [9]. According to these information and higher prevalence of some neuropathic pains, such as burning mouth syndrome and trigeminal neuralgia in female with more variant sex hormone status, the hypothesis of possible relation between sex hormones and prevalence of trigeminal neuralgia can be evaluated.
To the best of our knowledge, there is no study on sex hormones in patient with trigeminal neuralgia; hence, in this study FSH, LH, Testosterone, Estrogen, Progesterone serum levels in women affected by trigeminal neuralgia who had referred to Oral and Maxillofacial Disease Department of Shiraz Dental School, were evaluated.

Materials and Methods
This study is a cross sectional study, performed during 2017-18. The women with confirmed trigeminal neuralgia who had referred to Emam Reza clinic and Oral and Maxillofacial Disease Department of Shiraz Dental Faculty were enrolled in this study. The protocol of this study which was conducted according to the ethical principles of Helsinki [10], was approved by the ethics committee of Shiraz University of Medical Sciences (IR.SUMS.REC.1396.S886).
A written informed consent was obtained from each participant. The participants who had any disease that could affect sex hormone serum level were excluded from the study. The blood samples were obtained by an expert nurse in day 3 of participant's menstruation of nonmenopausal women; the day of sampling for menopausal women was not a specific day. The blood sample was obtained after 2-4 hours after waking up. The serum level of FSH, LH, Testosterone, progesterone, estrogen was evaluated. Patients' demographic data including age, other systemic disease and menopausal situation were registered. Twenty-six women with trigeminal neuralgia were recruited in case group and 26 healthy women whom their age were matched with TN group were enrolled in the healthy control group. The participants in healthy control group were patients who had referred to Shiraz Dental School for routine dental evaluation. Data was analyzed by SPSS version 18. The pattern of hormonal changes in menopausal and non-menopausal participants were compared by Mann-Whitney test.

Results
In this study, the mean age of participants in TN group was 52.73 ± 15.83 years old and 49.93 ± 12.04 for the healthy group. The mean serum level of evaluated sex hormones in TN and healthy control groups are presented in table 1. Other statistical data and the P value for comparing the mean of both groups are also in table 1.     [11][12][13][14][15] while others did not confirm this role [16][17][18][19][20]. In a study, the relationship between peripheral motor nerve status, estrogen serum level and progesterone was evaluated by Motor Nerve Conduction Velocity(MNCV) in post-menopausal women. In spite of significant lower serum level of estrogen in post-menopausal patient with peripheral neuropathy, no significant effect was reported for progesterone [9]. In another study, higher levels of progesterone was accompanied with reduced optic nerve conduction velocity [16]. Also elevated level of progesterone was considered to be effective in reducing the nerve conduction velocity in an evaluation [17]. On the other hand, animal model evaluation did not consider noticeable influence of estrogen and progesterone therapy on nerve repair [21]. The findings of these studies are in accordance with what we have reported in our study, in menopause participants which are considerably more prone to neuropathies, where a significant higher level of progesterone was reported in patients with TN compared to healthy controls. On the other hand, some other studies showed a neuroprotective and neurotrophic properties for progesterone. This role was reported in electrophysiological alteration of diabetic induced neuropathy in rats [15,22]. This neuroprotective effect was also reported for estrogen in some studies. A study proposed the protective effect of estrogen against neural death mediated by estrogen receptors. Estrogen can also regenerate the damaged nerves or enhance the nerve velocity and vascularity [8,12]. Several neuroprotective mechanisms in the literature have been proposed; for example, progesterone can induce regeneration and nerve demyelination which plays an important role in pathogenesis of most neuropathies [22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40]. In damaged nerves, progesterone prevents secondary neural losses by reducing edema, inflammatory cytokines and reactive gliosis [41]. Some studies reported that estrogen treatment can increase vascular epithelial growth factor expression, which suggests the pro-angiogenic properties of estradiol [42]. In the result of present study, rather than confirming the neuroprotective role of progesterone and estrogen, an imbalance of sex hormones in patients with TN was shown.

Conclusions
In spite of no significant differences in sex hormonal profile of patients with TN and healthy controls, the serum level of FSH in non-menopause TN participants and progesterone in menopause TN patients were significantly higher. These findings confirmed the sex hormonal imbalance of TN patients.

Authors' contributions
Fateme Lavaee and Parisa Mohaghegh Zahed were involved in study design, patients' evaluation and data interpretation. Fateme Zarei and Maryam Shahrokhi Sardo were involved in data acquisition and preparing the manuscript. All the authors read and approved the manuscript.

Data Availability
The readers can access the data supporting the conclusions of the study by a request through an email to the corresponding author.

Funding Statement
The Vice-Chancellor of Shiraz University of Medical Sciences supported this research. (grant #

Availability of data materials
The datasets used and/or analyzed during the study are available from the corresponding author on reasonable request.

Ethical approval and consent to participate
An informed consent was taken from all the participants before the study. This study was approved by the ethics committee of Shiraz University of Medical Sciences.

Consent for publication
Not applicable