Abstract
Although 17β-estradiol (E2) deficiency has been linked to the development of osteoarthritis (OA) in middle-aged women, there are few studies relating other estrogens and estrogen metabolites (EMs) to this condition. We developed a high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry (HPLC-ESI-MS/MS) method to measure the levels of six EMs (i.e., estrone, E2, estriol, 2-hydroxyestrone, 2-hydroxyestradiol, and 16a-hydroxyestrone) in healthy pre- and postmenopausal women and women with OA. This method had a precision ranging from 1.1 to 3.1% and a detection limit ranging from 10 to 15 pg. Compared to healthy women, serum-free E2 was lower in the luteal and postmenopausal phases in women with OA, and total serum E2 was lower in postmenopausal women with OA. Moreover, compared to healthy women, total serum 2-hydroxyestradiol was higher in postmenopausal women with OA and total serum 2-hydroxyestrone was lower in both the luteal and follicular phases in women with OA. In conclusion, our HPLC-ESI-MS/MS method allowed the measurement of multiple biochemical targets in a single assay, and, given its increased cost-effectiveness, simplicity, and speed relative to previous methods, this method is suitable for clinical studies.
Highlights
We developed a high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry (HPLC-ESI-MS/MS) method to measure the levels of six estrogen metabolites (EMs) in healthy pre- and postmenopausal women and women with OA
Estrogens are endogenous female hormones required for the growth and development of target tissues, including the mammary gland, and which play a major role in the etiology of breast cancer [1,2]
We found that a fixed-proportion mobile phase was unsuitable for quantitative analysis because it failed to separate the 6 EM reference substances effectively owing to the width of the chromatographic peaks
Summary
Estrogens are endogenous female hormones required for the growth and development of target tissues, including the mammary gland, and which play a major role in the etiology of breast cancer [1,2]. Estrogen metabolism has been related to osteoporosis and increased fracture risk [3,4], and lower baseline serum 17b-estradiol (E2) and urinary 2-hydroxyestrone (2-OHE1) levels have been linked to knee osteoarthritis (OA) in middle-aged women [5]. E1 generated by oxidation of E2 is hydroxylated via two mutually exclusive pathways [6] to generate either 2-hydroxyestrone (2-OHE1) or 16a-hydroxyestrone (16a-OHE1; Figure 1), which are estrogen agonists [7] with target tissue-specific biological activities distinct from one another and from E2. Compared to E2, 16a-OHE1 binds with lower affinity to both the estrogen receptor [8] and to serum sex hormone-binding globulin, and is
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Schedule a callMore From: Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas
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