Oxidative Stress: The Role of Estrogen and Progesterone

Angelo Cagnacci; Irene Gazzo; Sara Stigliani; Anna Maria Paoletti; Paola Anserini; Ambrogio Pietro Londero; Anjeza Xholli

doi:10.3390/jcm12237304

Oxidative Stress: The Role of Estrogen and Progesterone

J Clin Med. 2023 Nov 25;12(23):7304. doi: 10.3390/jcm12237304.

Authors

Angelo Cagnacci^{1

2}, Irene Gazzo^{1

2}, Sara Stigliani³, Anna Maria Paoletti⁴, Paola Anserini^{1

3}, Ambrogio Pietro Londero², Anjeza Xholli¹

Affiliations

¹ Obstetrics and Gynecology Teaching Unit, IRCCS Ospedale Policlinico San Martino, 16132 Genoa, Italy.
² Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Infant Health, University of Genoa, 16132 Genova, Italy.
³ Physiopathology of Human Reproduction, IRCCS Ospedale Policlinico San Martino, 16132 Genoa, Italy.
⁴ Obstetrics and Gynecology Teaching Units, Azienda Ospedaliera Universitaria di Cagliari, 09124 Cagliari, Italy.

Abstract

The effect of estrogen and progesterone on oxidative status is not yet very clear, improvements and detrimental effects having been reported with the use of menopausal hormone therapy or hormonal contraceptives, respectively. In this study, we evaluated the role played by estrogen and progesterone separately, on the oxidative status of 32 women, 18 to 43 years old, by inducing high levels of estrogen and then adding high levels of progesterone. During a cycle of in vitro fertilization, blood samples were collected prior to gonadotrophin stimulation (low estradiol levels), on the day of oocyte retrieval (high levels of estrogen), and on the day of embryo transfer (high levels of estrogen and progesterone). Total blood levels of oxidants (FORT), antioxidants (FORD), and their ratio FORT/FORD were measured using a colorimetric method based on the Fenton reaction. Seven women measured their early morning body temperature at the same time points. FORT significantly decreased from the low- to the high-estrogen phase (p = 0.023) and increased from the high-estrogen to the high-estrogen-progesterone phase (p = 0.006). FORD showed an opposite but non-significant trend. The FORT/FORD ratio decreased from the low- to the high-estrogen phase (p = 0.0104) and increased from the high-estrogen to the high-estrogen -progesterone phase (p = 0.004). Body temperature (n = 7) decreased in the high-estrogen phase (p = 0.001) and increased from the high-estrogen to the high-estrogen-progesterone phase (p = 0.001). In the seven women, FORT (p = 0.009) and FORT/FORD (p = 0.0056) were linearly related to body temperature values. Our data show opposite effects of estrogen and progesterone on oxidative status. These effects seem to be related to the effect exerted on body temperature regulation.

Keywords: ROS; antioxidant; cancer; cardiovascular disease; contraception; hormonal contraceptives; menstrual cycle; ovarian stimulation; oxidative stress.

Grants and funding

This research was funded by the Italian Minister of Health, DGPRFEV/P/F.3.a.d/2019/1016 for the project “Oxidative stress and unexplained sterility: correlation with causal factors” grant number CUP G38D1900099000.