The Possibly Reversible Isotretinoin Effect of Decreased Ovarian Reserve in Sprague-Dawley Albinos: Part I, Biochemical Analyses

Abstract

Background: The study aims to determine the detrimental effects of 7.5 mg/kg/day isotretinoin treatment on the anti-Mullerian hormone (AMH) levels in an experimental study to see whether the effects on ovarian reserve are reversible. Methods: Blood was sampled in 16 Sprague-Dawley albinos before any treatment to see baseline AMH levels. Then, the rats were randomly divided into 2 groups. Control group received only 1.0 ml soybean oil per oral for 30 days, whereas the study group received 7.5 mg/kg/day isotretinoin suspended in soybean oil. AMH levels were measured at the 30th day - immediately after the last medication - and on 60th day - 1 month after the last medication. Results: The mean values of AMH levels were 8.16 ± 1.47, 6.95 ± 1.87, 6.27 ± 0.71 and 8.20 ± 1.48, 6.56 ± 1.45, 7.07 ± 0.96 ng/ml before, immediately after and 1 month after the last medication in the control and isotretinoin treatment group, respectively. The mean AMH levels significantly decreased (p = 0.02) immediately after isotretinoin administration. The mean AMH levels 1 month after the last dose of isotretinoin therapy were higher than the levels immediately after the medication; however, the difference was not statistically significant. Conclusion: This study indicates that exposure to isotretinoin is responsible for decreased AMH levels in experimental rat model and this effect seems to be reversible.

Anti- Müllarian hormone (AMH) as an indicator of ovarian reserve in acne patients treated with isotretinoin

“…Furthermore, no statistically significant changes in AMH values 1 month after the last dose of isotretinoin relative to pretreatment values were found. These results indicate that after isotretinoin cessation, AMH concentrations increased, providing additional evidence for the first time in the literature, suggesting that the impact of isotretinoin on ovarian reserves could be reversible [13].…”

“…In contrast to previous research, Korkmaz et al [13] tested AMH values prior to drug administration, as well as AMH values immediately after and one month after the last dose of isotretinoin administration, to see whether there was any drug impact and how long it lasted. While there were no major differences between the groups, the isotretinoin treatment group's AMH values were slightly lower on the day immediately following the last dose (p = 0.02) than the pretreatment values.…”

“…According to Aksoy et al, [12], major variations in AMH [2.20 ng/ml (25th-75th percentile 1.14-4.07) vs. 1.31 ng/ml (0.32-2.28); p 0.001], total AFC [16 (14-18.25) vs. 12.5 (10-15); p 0.001], and total OV (ovarian volume) [23 ml (18-29) v Korkmaz et al [13] measured serum AMH levels before administering isotretinoin to all rats in their sample. The lack of a statistically significant difference between the study groups in terms of pre-isotretinoin AMH values resulted in two identical study groups with comparable ovarian reserves, except variations related to intrinsic rat ovarian function.…”

The Effect of Isotretinoin on Oocyte Maturation in Adolescent Female Rats

“…However, several clinical studies investigating the effects of isotretinoin on female fertility have been reported to reduce ovarian reserves [10-12]. Similar data have been reported in animal studies in which rats were treated with 7.5 and 15 mg/kg/day isotretinoin [13, 14]. However, these studies investigating the toxic effects of isotretinoin on reproductive organs are few [15, 16].…”

“…In a clinical study, it has been reported that systemic treatment with isotretinoin has no long-term side effects on fertility in humans [28]. However, in an animal study, the reversible effect of isotretinoin on the ovaries was examined [14]. In this study, basal AMH levels of blood samples of 16 Sprague-Dawley albinos were measured before isotretinoin administration, and then rats were randomly divided into 2 groups: 0 mg/kg/day (group 1) and 7.5 mg/kg/day (group 2).…”