Kimberly S Ryan1, Shruthi Mahalingaiah2,3, Lily R Campbell4, Victoria H J Roberts5, Juanito Jose D Terrobias5, Chelsey S Naito5, Emily R Boniface1, Laura M Borgelt6, Jason C Hedges7, Carol B Hanna5, Jon D Hennebold1,5, Jamie O Lo1,5. 1. Department of Obstetrics and Gynecology, Division of Maternal Fetal Medicine, Oregon Health & Science University, Portland, Oregon. 2. Department of Environmental Health, Harvard T. H. Chan School of Public Health, Boston, Massachusetts. 3. Massachusetts General Hospital Fertility Center, Department of Obstetrics, Gynecology, and Reproductive Biology, Division of Reproductive Endocrinology and Infertility, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts. 4. Department of Biology, Boston University, Boston, Massachusetts. 5. Division of Reproductive and Developmental Sciences, Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, Oregon. 6. Department of Clinical Pharmacy and Family Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado. 7. Department of Urology, Oregon Health & Science University, Portland, Oregon.
Abstract
OBJECTIVE: To determine the dose-dependent effect of contemporary marijuana exposure on female menstrual cyclicity and reproductive endocrine physiology in a nonhuman primate model. DESIGN: Research animal study. SETTING: Research institute environment. ANIMALS: Adult female rhesus macaques (6-12 years of age; n = 8). INTERVENTIONS: Daily delta-9-tetrahydrocannabinol (THC) edible at medically and recreationally relevant contemporary doses. MAIN OUTCOME MEASURES: Menstrual cycle length (MCL), anti-Müllerian hormone, prolactin, basal follicle-stimulating hormone (FSH), estradiol (E2) and progesterone, luteinizing hormone (LH), and thyroid-stimulating hormone. RESULTS: The average before THC weight was 6.9 kg (standard deviation, 0.8), and at the highest THC dosing, the average weight was 7.2 kg (standard deviation, 0.8). With increasing THC dosing, MCL and FSH concentrations increased, while basal E2 concentration was stable. The average MCL concentration increased 4.0 days for each mg/7 kg/day of THC (95% CI, 1.4-6.6 days). Follicle-stimulating hormone concentration increased significantly with increasing THC dose, 0.34 ng/mL for each mg/7 kg/day of THC (95% CI, 0.14-0.57 ng/mL). No significant trends were observed between THC dosing and average basal progesterone, anti-Müllerian hormone, prolactin, LH, or thyroid-stimulating hormone concentrations. CONCLUSIONS: In rhesus macaques, a dose response toward increased MCL and basal FSH concentrations but plateau of basal E2 and LH concentrations was observed with increasing THC dosing, suggesting ovulatory dysfunction. Further studies are needed to determine the effects of a longer duration of exposure and whether the significant increase in MCL and FSH concentrations results in reduced fecundity.
OBJECTIVE: To determine the dose-dependent effect of contemporary marijuana exposure on female menstrual cyclicity and reproductive endocrine physiology in a nonhuman primate model. DESIGN: Research animal study. SETTING: Research institute environment. ANIMALS: Adult female rhesus macaques (6-12 years of age; n = 8). INTERVENTIONS: Daily delta-9-tetrahydrocannabinol (THC) edible at medically and recreationally relevant contemporary doses. MAIN OUTCOME MEASURES: Menstrual cycle length (MCL), anti-Müllerian hormone, prolactin, basal follicle-stimulating hormone (FSH), estradiol (E2) and progesterone, luteinizing hormone (LH), and thyroid-stimulating hormone. RESULTS: The average before THC weight was 6.9 kg (standard deviation, 0.8), and at the highest THC dosing, the average weight was 7.2 kg (standard deviation, 0.8). With increasing THC dosing, MCL and FSH concentrations increased, while basal E2 concentration was stable. The average MCL concentration increased 4.0 days for each mg/7 kg/day of THC (95% CI, 1.4-6.6 days). Follicle-stimulating hormone concentration increased significantly with increasing THC dose, 0.34 ng/mL for each mg/7 kg/day of THC (95% CI, 0.14-0.57 ng/mL). No significant trends were observed between THC dosing and average basal progesterone, anti-Müllerian hormone, prolactin, LH, or thyroid-stimulating hormone concentrations. CONCLUSIONS: In rhesus macaques, a dose response toward increased MCL and basal FSH concentrations but plateau of basal E2 and LH concentrations was observed with increasing THC dosing, suggesting ovulatory dysfunction. Further studies are needed to determine the effects of a longer duration of exposure and whether the significant increase in MCL and FSH concentrations results in reduced fecundity.
Authors: Lauren A Wise; Amelia K Wesselink; Elizabeth E Hatch; Kenneth J Rothman; Ellen M Mikkelsen; Henrik Toft Sørensen; Shruthi Mahalingaiah Journal: J Epidemiol Community Health Date: 2017-12-22 Impact factor: 3.710
Authors: Stéphanie E Reitsma; Hari Hara Sudhan Lakshmanan; Jennifer Johnson; Jiaqing Pang; Iván Parra-Izquierdo; Alex R Melrose; Jaewoo Choi; Deirdre E J Anderson; Monica T Hinds; Jan Frederik Stevens; Joseph E Aslan; Owen J T McCarty; Jamie O Lo Journal: Am J Physiol Cell Physiol Date: 2022-01-26 Impact factor: 4.249
Authors: Jason C Hedges; Carol B Hanna; Jasper C Bash; Emily R Boniface; Fernanda C Burch; Shruthi Mahalingaiah; Victoria H J Roberts; Juanito Jose D Terrobias; Emily C Mishler; Jared V Jensen; Charles A Easley; Jamie O Lo Journal: Fertil Steril Date: 2022-01-25 Impact factor: 7.490