Nandrolone treatment of adolescent female rats alters reproductive tissue and gonadal steroid profile
Authors: Rivero Carlos , Freire Jaime , Siaca Paula , Rendon Luis , Roa Patricia , Ortiz Natalia , Segarra Annabell 
Published: May 2024

Anabolic androgenic steroids (AAS) are drugs that mimic the chemical structure of testosterone. The most commonly AAS used by young adults is nandrolone. In the USA, more than 20 % of AAS users started using steroids before the age of 20. This is alarming as most female users are unaware of the detrimental reproductive effects of AAS use such as amenorrhea, anovulation and clitoromegaly. An additional detrimental effect of AAS is their addictive liability. Previous studies indicate that animals self-administer AAS. Furthermore, AAS can cross-sensitize with other drugs of abuse such as cocaine. Our goal was to elucidate the effects of both AAS and cocaine in the reproductive system of female rats. Our hypothesis is that AAS will have a detrimental effect on the reproductive system of female rats. Adolescent female rats were divided into two large groups, one that received nandrolone decanoate (20mg/kg/sc) and another that received sesame oil (vehicle) for 10 successive days starting on day 28. Animals were further subdivided into groups that received saline or cocaine injections (0.01cc/10g) for a total of 4 groups: Oil-Saline, ND-Saline, Oil-Cocaine and ND-Cocaine. One cohort (Day 40) received cocaine or saline injections (0.01cc/10g) from days 40 to 44 and on days 52 and day 62. The other cohort (Day 65) received cocaine or saline injections from days 65 to 69 and on days 77 and 87. Our data show that administration of nandrolone during adolescence increased body weight of female rats. Ovarian weight was decreased, and ovarian tissue presented multiple cysts with fewer follicles. Nandrolone also disrupted uterine morphology. The uterine lumen was increased, the endometrial thickness reduced and thickness of myometrial tissue, as well as uterine weight, was increased. In addition, nandrolone reduced both endometrial estrogen and androgen receptors, an effect lost by day 88. In contrast, uterine tissue at day 63 showed an increase in progesterone receptor (PR) immunoreactivity, whereas PR immunoreactivity decreased in tissue obtained at Day 88 regardless of whether animals had received cocaine. Cocaine also increased PR receptors in uterine tissue at day 63 and 88. Animals treated with nandrolone had higher serum concentrations of testosterone and estradiol and a lower level of progesterone. These data show that nandrolone when administered in supraphysiologic doses during adolescence, has long lasting effects on the reproductive system of the female rat due to the depot effects and long half-life of this drug. These data warrant further research in this area to determine the long-term consequences of early nandrolone exposure on the female reproductive system, as well as fertility.

Financial assistance was provided by the Offce of International Science and Engineering (OISE) of NSF through the Partnerships for Research and Education (PIRE) Program (OISE-#1545803).

This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.