Background—The incidence and prevalence of infertility and sexual dysfunction in men and women is increasing. The biogenic polyamines spermine and spermidine are important for sexual function as well as fertility. Spermine and spermidine are present in plant foods and synthesized from ornithine and methionine in mammals. Stress and stress-associated hormone disruption are contributors to both poor sexual function and infertility. Spermine and spermidine are important in reducing the impact of stress on living organisms. Objective—This open-label pilot trial was designed to determine the impact of spermine and spermidine supplementation on hormone levels of otherwise healthy human subjects with no history of infertility or sexual dysfunction over a 30-day period. Pre and post supplement levels of cortisol, DHEAS, testosterone, progesterone and estradiol as well as 30-day post supplement levels of these hormones were performed on age/gender equivalent subjects. A total of 15 individuals participated in the study. Informed consent forms were executed along, with adverse events reporting information. Results—Clinically significant reductions (p-value less than 0.05) in cortisol were seen in 30 days among 83% of male participants and 37% of female participants. Sixty-six percent of male participants maintained lower cortisol levels 30 days after withdrawal of the study supplement. In women, the cumulative effect of the spermine and spermidine supplementation continued with 50% reporting a significant reduction in cortisol levels 30 days after withdrawal of the study supplement. There was an average of 3.3 pounds of weight loss during the first 30 days of supplementation without any dietary or metabolic intervention. Further, 7 out of 8 female participants demonstrated a moderate increase in DHEAS at 30 days, while 5 out of 7 male participants demonstrated a significant Dehydroepiandrosterone (DHEAS) increase in 60 days. Eighty-three percent of men had a decrease in estradiol and 100% of men had a decrease of pro