In addition, (De Giacomo et al., 2016) examined 88 patients with autism spectrum disorder aged 2 to 11 years, 81 were boys, and reported aggression towards caregivers to be present in 47% of patients in both verbal and non-verbal groups. Also the patients showed aggression towards other people and towards self but with insignificant difference.
Also it agrees with (S. Patel, Day, Jones, & Mazefsky, 2017) who studied 25 adolescents with ASD, aged 12 to 19 years and 24 controls and concluded that autistic patients had more significant levels of anger rumination.
(Mazefsky, Pelphrey, & Dahl, 2012) also mentioned that patients with autism are more likely to focus on negative thoughts and experiences, which can contribute to the occurrence of depression or hostile behaviors.
This can be highlighted at the time of adolescence leading to deterioration in autistic patients as reported by (Picci & Scherf, 2015) due to the hormonal variations and their accompanied mood changes.
In our study, there was a non-significant relationship between aggression and levels of FSH, LH and free testosterone. This is against the findings of (Sylvie Tordjman et al.
, 1997) who studied 9 patients with autism and found that the group that exhibited aggression against others had plasma testosterone concentration values higher than other subjects.
It is also against the results of the pilot study of (Anna Pivovarciova et al., 2014) who reported elevated level of testosterone in one of the three patients with autism and that patient showed aggressive behavior.
Inappropriate sexual behavior in adolescents with ASD is a relatively common problem, and is related to the lack of understanding of normal puberty, lack of appropriate sex education, medications and problems associated with their ASD (Beddows & Brooks, 2016).
Despite the high prevalence of increased sexual behaviors among autistic patients, there has been few epidemiological data (Deepmala & Agrawal, 2014).
The reason for the limited information could be related to the sensitive nature of the subject and for cultural and religious causes, as it is very distressing for the family (McLay, Carnett, Tyler-Merrick, & van der Meer, 2015). Although there is lack of an agreed upon definition, inappropriate sexual behavior can be used to describe acts that are excessive, in front of others or violating others privacy, aggressive or considered adult acts (McLay et al., 2015).
As regards inappropriate sexual behavior, our study showed that 40% of patients showed inappropriate sexual behavior, mainly in the form of masturbation among others. This can be compared to that of (David A Geier & Mark R Geier, 2006), who studied 16 children with autistic spectrum disorder aged ? 11 years, 14 of whom were males, and found that 4 patients (25%) suffered from aggression, 5 patients (31.25%) had inappropriate sexual behavior, mainly masturbation and 5 patients (31.25%) had both problems.
Inappropriate sexual behaviors in autistic children were reported by teachers who even related the severity of these symptoms to the level of functioning of autism, with more severe symptoms in lower functioning patients. They explained this by less understanding of social rules and privacy issues (Kalyva, 2010).
In stage 2 of our study we divided the patients into 2 groups according to their hormonal profile and behavioral disturbance into 10 patients who were suspected to have accelerated pubertal development and 25 patients not suspected to have these abnormalities. By comparing both groups we found that the first group were older, 3 patients were Tanner 2 stage as compared to the other group who were all Tanner 1. FSH SDS was high in 30% of the first group compared to 20% of the second group. Also the first group had higher free testosterone levels compared to the second group. Finally the first group had more prevalent behavioral problems as 80% were aggressive versus 36% in the second group, and 70% had inappropriate sexual behavior in the first group versus 24% in the second group.
We gave the 1st group of patients (10 patients) one leuprolide acetate depot (lupron®) 11.25 mg single IM injection each and followed them after 3 and 6 months.
Regarding the effect on hormones, there was a highly significant decrease in the level of FSH at 3 months which persisted at 6 months follow up.
However, there was a non-significant change in the levels of LH and free testosterone, despite 2 patients showing return of free testosterone near the baseline level after 6 months indicating washout of Lupron. This could be explained by the fact that most of our patients were prepubertal (91.4%) and thus the hypothalamic-pituitary-gonadal axis is still inactive.
There was no correlation between CARS score and levels of FSH, LH and free testosterone initially or after 6 months but there was a negative correlation between CARS score and free testosterone levels at 3 months.
As regards behavioral problems, there was insignificant change in the level of aggression during the follow up period, indicating poor response or the presence of other confounders affecting the level of aggression in the study population, or may be merely due to the small sample size.
This disagrees with the case reported by (van der Weiden, Helmerhorst, & Eriksson, 2016) who reported marked improvement in the level of aggression in a young patient with autism after receiving GnRH analogues and the beneficial effect started to appear after 6 months of treatment.
Also there was no relation between the presence of aggression and levels of FSH, LH and free testosterone initially, after 3 months and after 6 months.
This is in agreement with the case presented by (van der Weiden et al., 2016) where the autistic patient with high levels of aggression had normal baseline levels of androgens.
However, it disagrees with the findings of (D. A. Geier & M. R. Geier, 2006) who reported that combined therapy with GnRH analogues and antiheavy metals was effective in decreasing aggressive behavior in 11 children with ASD and elevated androgens.
On the other hand, there was a highly significant improvement of inappropriate sexual behavior after 3 months of treatment which even persisted after 6 months, although the effect of Lupron should have disappeared by then.
Consequently, there was a significant improvement in the group who suffered both aggression and inappropriate sexual behavior also after 3 months and the effect persisted at 6 months follow up. This could explained by the relationship between inappropriate sexual behavior and aggression which was demonstrated initially.
This is also supported by the case published by (Eyuboglu, Eyuboglu, & Yilmaz, 2018) who showed significant improvement in deviant sexual behavior in a 13 years old male as well as aggressive behavior following GnRH analogue therapy for 3 months.
However, there was non-significant relationship between treatment with Lupron and the severity of autism by CARS and ATEC scores, initially and at 3 and 6 months follow up, indicating that its not a line of treatment for autism by itself but can improve associated symptoms.
On the other hand, (D. A. Geier & Geier, 2007) reported significant improvement in the overall functioning related to autism, with reduced ATEC scores and improved abnormal sexual behaviors following leuprolide therapy to 200 patients with ASD.
As for the anthropometric measures of our patients 88.6% of patients had normal height SDS for age, 5.7% had a low height SDS and 5.7% had a high height SDS for age.
Also 74.3% of patients had a normal BMI SDS, 17.1% had a low BMI SDS and 8.6% had a high BMI SDS.
As for bone age SDS, 74.3% of patients had a normal bone age SDS, 5.7% had a delayed bone age SDS and 20% had an advanced bone age SDS.
Our study agrees with those of (Abdul-Rasheed, 2016) who studied autistic patients with a mean age 7.28 years and reported normal height and BMI.
It also agrees with (Xiong et al., 2009) who studied autistic patients, 2 11 years old and reported normal height and BMI.
Moreover, it agrees with (Curtin, Bandini, Perrin, Tybor, & Must, 2005) who studied autistic patients aged 3 -18 years and reported normal BMI results compared to the normal population.
On the other hand, (Mraz, Dixon, Dumont-Mathieu, & Fein, 2009) reported increased height compared to CDC scores.
Further, (Whiteley, Dodou, Todd, & Shattock, 2004) studied autistic patients 2-12 years old and found elevated height and BMI but to insignificant levels.
Our study agrees with that of (Mills et al., 2007) who studied autistic patients 4-8 years who also found normal height and bone age, but we disagree with his results of higher BMI. Increased BMI could be explained by several factors as environmental or medications.
As 17.1% of our patients had a low BMI SDS, this agrees with (Mouridsen, Rich, & Isager, 2002) who studied autistic patients aged 2- 15 years and found reduced BMI levels.
Finally, (Wolf & Goldberg, 1986) studied a group of autistic patients aged 1-15 years and followed them up for 8- 24 years and reported that 63% had delayed bone age, 22% had advanced bone age and 15% had a normal bone age.
Although several studies have mentioned advanced growth rates among autistic children, most of those refer to early infancy while our patients were in the range of 6 till 11 years which is the time of slowing of growth rates in autism according to (Green, Dissanayake, & Loesch, 2015), which can explain that most of our patients had normal height SDS (88.6%)and normal BMI SDS (74.3%).
Also difference in physical growth can be related to several factors as parents height, diet, exercise, medications intake and their side effects.
Among those who received Lupron, there was no significant changes regarding height SDS, BMI SDS or bone age SDS during the follow up period of our study, indicating no adverse effects on growth.