Does ivermectin use lower sperm count?

Comment by InpharmD Researcher

There is little data on the effect of ivermectin on human fertility. A human study in patients with onchocerciasis found ivermectin to be associated with adverse effects on the sperm functions. Animal studies suggest sperm abnormalities may be seen with ivermectin use, especially at higher doses.

Background

A 2011 observational study was performed on 37 Nigerian patients with onchocerciasis to evaluate the effects of ivermectin on sperm function. Patients who were 28 to 57 years old and had normal sperm count at baseline were included in the study. The sperm function was examined by analysis of seminal fluid. Sperm counts, sperm motility, sperm morphology, sperm volume, sperm viscosity, and sperm liquefaction time were measured before and after the treatment with ivermectin (150 μg/kg body weight). A significant reduction in the mean sperm counts was reported (109.8 million/ml before vs. 89.1 million/ml after the treatment). Mean sperm motility was significantly reduced after ivermectin treatment (72% before vs. 41.9% after treatment). The mean of sperms with abnormal morphology was also increased post ivermectin treatment (25% before vs. 55.1% after treatment). No significant change was observed regarding the sperm viscosity, sperm volume, and sperm liquefaction time. Overall, it was concluded that caution should be exercised in the treatment of male onchocerciasis patients with ivermectin to avoid the adverse effects it has on the patients’ sperm functions; however, the study was limited due to lack of a meaningful measurement for a significant result. [1]

An animal study in 2008 examined the effect of ivermectin on male fertility in rats and evaluated its interaction with verapamil regarding different sperm parameters, weights and histopathological examination of the reproductive organs, and cytogenetic examination of germ cells. Adult male Wister rats were studied in four groups: Intraperitoneal (IP) physiological saline (2 ml/kg body weight) was given to group 1 once weekly and propylene glycol (2 ml/kg body weight) was used after one hour as a vehicle. Group 2 received IP saline once weekly and received ivermectin 1% (300 µg/kg body weight) after one hour. Group 3 received IP verapamil (3 mg/kg body weight) once weekly and propylene glycol after one hour. Group 4 received IP verapamil (3 mg/kg body weight) once weekly and IP ivermectin (300 µg/kg body weight) was given after one hour. [2]

The rat reproductive organ relative index weight (IW) for testis, epididymis, and accessory sex organ was examined and a slight reduction of IW was seen in the ivermectin group compared to the control group (1.1 ± 0.05 vs. 0.4 ± 0.02 vs. 0.95 ± 0.02 respectively in ivermectin group compared to 1.4 ± 0.05 vs. 0.54 ± 0.01 vs. 1.07 ± 0.06 respectively in the control group; p= 0.05). The use of ivermectin plus verapamil resulted in higher reduction rates in the weights of these organs. While administering ivermectin once weekly for eight weeks did not decrease mounting behavior compared to control significantly, the use of verapamil prior to ivermectin showed a significant decline in the mounting behavior in rats (p ≤ 0.05). Sperm motility percentage showed ivermectin alone did not decrease sperm motility significantly compared to the control group (74.1 ± 5.0 vs. 80.8 ± 1.5 respectively). Significant higher levels of sperm abnormalities were only seen in the verapamil and ivermectin-treated group. [2]

One 2017 in-vivo study examined the influences of ivermectin at the therapeutic dose of 0.56 mg/kg on the expression of testicular insulin-like growth factor binding protein-3 (IGFBP-3), heat-shock protein A1 (HSPA1) genes in the testes, and male rat fertility parameters. Injection of ivermectin, compared with the control, was associated with a significant decrease in serum testosterone level 1.78 ± 0.22 vs 2.28 ± 0.33 ng/mL, sperm cell count 186.25 ± 1.84 vs 321.25 ± 1.22 (x106/mL), sperm motility 67.50 ± 2.44 vs 90.00 ± 2.23 (%), and increase in sperm abnormalities 16.5 ± 1.16 vs 10 ± 0.6 (%), respectively (p ≤ 0.05); the rat reproductive organ relative index weight (I.W.; organ weight [gm]/body weight [gm]), designated by I.W. of testes (gm/100 mg b.wt), I.W. of epididymis (gm/100 gm b.wt), and I.W. of accessory sex organs (gm/100 gm b.wt) were also significantly reduced in the ivermectin group than the control, 1.07 ± 0.07 vs 1.55 ± 0.04, 0.59 ± 0.04 vs 0.74 ± 0.02, and 0.82 ± 0.06 vs 0.88 ± 0.04, respectively (p ≤ 0.05). Additionally, expression of IGFBP-3 and HASPA1 to 11.31 ± 1.50 and 6.68 ± 1.13 relative to the control were also significantly observed in the ivermectin-treated group, indicating the adverse effect of using drugs on male fertility and cellular protective mechanisms. Based on the study results, the authors concluded unfavorable effects of ivermectin on male fertility and potential alternations of the related genes in male rats. [3]

References:

[1] Idonije OB, Asika EC, Okhiai O, et al. Effects of Ivermectin therapy on the sperm functions of Nigerian onchocerciasis patients. Scholars Research Library. 2011, 3 (3):533-543.
[2] El-Nahas AF, El-Ashmawy IM. Effect of ivermectin on male fertility and its interaction with P-glycoprotein inhibitor (verapamil) in rats. Environ Toxicol Pharmacol. 2008;26(2):206-211. doi:10.1016/j.etap.2008.03.011
[3] El-Maddawy ZK, Abd El Naby WSH. Effects of ivermectin and its combination with alpha-lipoic acid on expression of IGFBP-3 and HSPA1 genes and male rat fertility. Andrologia. 2018;50(3):10.1111/and.12891. doi:10.1111/and.12891

Relevant Prescribing Information

Carcinogenesis, Mutagenesis, Impairment of Fertility:
Long-term studies in animals have not been performed to evaluate the carcinogenic potential of ivermectin. Ivermectin was not genotoxic in vitro in the Ames microbial mutagenicity assay of Salmonella typhimurium strains TA1535, TA1537, TA98, and TA100 with and without rat liver enzyme activation, the Mouse Lymphoma Cell Line L5178Y (cytotoxicity and mutagenicity) assays, or the unscheduled DNA synthesis assay in human fibroblasts.
Ivermectin had no adverse effects on the fertility in rats in studies at repeated doses of up to 3 times the maximum recommended human dose of 200 mcg/kg (on a mg/m2/day basis).
In a fertility study, oral doses of 0.1, 1 and 9 mg/kg/day ivermectin were administered to male and female rats. Mortality occurred at 9 mg/kg/day (1027X MTHD). The precoital period was generally prolonged at 9 mg/kg/day. No treatment-related effects on fertility or mating performance were noted at doses ≤ 1 mg/kg/day (68X MTHD).

References:

Ivermectin [prescribing information]. Parsippany, NJ: Edenbridge Pharmaceuticals, LLC; 2017.