The biological effect of progestins on anterior knee laxity in females on oral contraceptives

UNCG Author/Contributor (non-UNCG co-authors, if there are any, appear on document)
Elvis M. Foli (Creator)
The University of North Carolina at Greensboro (UNCG )
Web Site:
Sandra Shultz

Abstract: Injuries to the anterior cruciate ligament (ACL) are more likely to occur in females and sex hormones have been implicated in this sex-based injury disparity. Research suggests naturally produced sex hormones influence anterior knee laxity (AKL), a risk factor for ACL tears. A significant proportion of athletic females take hormonal oral contraceptive pills (OCPs), which reduce circulating levels of endogenously produced sex hormones. These pills contain a class of progesterone-like hormones called progestins, which exert both progestational and androgenic effects on soft tissue. The pharmacodynamic effect of these compounds varies across OCP brands as different types and doses of progestins are used in modern OCPs, and therefore the effect of OCP use on AKL is unclear. The purpose of this study three-fold: 1) determine an appropriate biochemical assay to measure progestins in the serum of active females on oral contraceptives. 2) compare the pharmacodynamic activity that was “prescribed” on OCP pill packages to the measured activity measured by the hormone assay, and 3) to examine the effects of progestins with different levels of androgenicity and progestational activity or potency on AKL Forty-five recreationally active females using OCPs were projected to be recruited and stratified and placed into three groups based on the pharmacodynamic activity of the OCPs used by the subjects. However, due to restraints imposed by COVID, a total of sixteen females were recruited, and group stratification was not possible. Blood samples were collected from participants during their third and fourth pill weeks. Concentrations of two common progestins, norethindrone and levonorgestrel were measured using a Waters Acquity Ultra Performance Liquid Chromatography system coupled to an LTQ Orbitrap XL Mass Spectrometer, and AKL was measured using the KT2000 knee arthrometer. Validation analyses commonly used in analytical chemistry were used to assess the performance of a UPLC-MS method created for this thesis. Simple bivariate correlational analyses between pill/serum potency and androgenicity and AKL were used to examine the associations between potency and androgenicity at the third pill week and the change in AKL from pill week three to pill week four (?AKL). Associations between pill/serum potency and androgenicity with AKL during the third pill week were largely non-significant. However, there was a significant association between peak serum androgenicity and ?AKL from week 3 to week 4. Additionally, in a sub-set of participants whose metabolized progestin was levonorgestrel (LNG), there was a significant positive association between peak serum potency/androgenicity and ?AKL on the left leg. While there were few significant findings due to low statistical power, the results of this thesis lay a valuable and informative foundation from which to further examine the effects of OCPs on AKL in active women. [This abstract may have been edited to remove characters that will not display in this system. Please see the PDF for the full abstract.]

Additional Information

Language: English
Date: 2021
ACL Injury, Anterior Knee Laxity, Birth Control, Knee Injury, Oral Contraceptive Pills, Women
Anterior cruciate ligament $x Wounds and injuries $x Prevention
Women athletes $x Health and hygiene
Oral contraceptives $x Side effects

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