Chronic THC use caused testicular shrinkage, hormone changes, and sperm DNA modifications in rhesus macaques, with partial but incomplete recovery after stopping use.
Reproductive endocrinologists, fertility specialists, and men concerned about cannabis effects on fertility.
59% testicular volume decreasewith chronic THC in macaques, recovering to only 73% of original volume after cessation
What the researchers found
THC caused 59% decrease in testicular volume, decreased testosterone and estradiol, increased FSH, and altered 23,558 CpG methylation sites in sperm DNA. After cessation, testicular volume recovered to 73% and hormones partially normalized.
Why it matters
This is the first study in primates showing that while THC damage to male reproductive health is partially reversible, some effects — particularly epigenetic changes in sperm — may persist after stopping use.
The numbers in context
6 adult male rhesus macaques (age 8-10). 59% decrease in testicular volume per 1 mg/7kg/day increase. Recovery to 73% of original volume. Testosterone increased 1.3 ng/mL after cessation. 23,558 differentially methylated CpGs in sperm.
How the study worked
Research animal study with chronic daily THC edible administration at medically/recreationally relevant doses followed by cessation, with testicular imaging, hormone assays, semen analysis, proteomics, and whole genome bisulfite sequencing.
Who was studied
6 adult male rhesus macaques (age 8-10 years) in a controlled research setting.
What this study cannot tell us
Small sample size (n=6). Rhesus macaques may not perfectly model human reproductive biology. Recovery period may need to be longer. Cannot determine if epigenetic changes affect offspring health.
How to read the evidence
Primate model with medically relevant dosing provides strong translational evidence, though small sample limits statistical power.
When this study was published
Recent primate study using contemporary relevant THC doses.
The bigger picture
With cannabis use increasing among reproductive-age men, these primate data provide the strongest evidence yet that THC affects male fertility through multiple mechanisms and that damage may not fully reverse after stopping use.
Replication
First primate cessation study; small sample (n=6) warrants larger replication.
Funding
Not specified in abstract
Conflicts of interest
Not specified in abstract
Questions still open
- Do the persistent sperm epigenetic changes affect offspring development?
- How long does complete recovery take, if it occurs at all?
Read the original research
Cessation of chronic delta-9-tetrahydrocannabinol use partially reverses impacts on male fertility and the sperm epigenome in rhesus macaques.
Fertility and sterility, 120(1), 163-174
Citation
Hedges, Jason C; Hanna, Carol B; Shorey-Kendrick, Lyndsey E; Boniface, Emily R; Bash, Jasper C; Rice-Stitt, Travis L; Burch, Fernanda C; D'Mello, Rahul; Morgan, Terry K; Lima, Ana Cristina; Terrobias, Juanito Jose D; Graham, Jason A; Mishler, Emily C; Jensen, Jared V; Hagen, Olivia L; Urian, J Wes; Spindel, Eliot R; Easley, Charles A; Murphy, Susan K; Lo, Jamie O. (2023). Cessation of chronic delta-9-tetrahydrocannabinol use partially reverses impacts on male fertility and the sperm epigenome in rhesus macaques.. Fertility and sterility, 120(1), 163-174. https://doi.org/10.1016/j.fertnstert.2023.02.034