Reexamination of testosterone, dihydrotestosterone, estradiol and estrone levels across the menstrual cycle and in postmenopausal women measured by liquid chromatography-tandem mass spectrometry
Open accessAbstract
Measuring serum androgen levels in women has been challenging due to limitations in method accuracy, precision sensitivity and specificity at low hormone levels. The clinical significance of changes in sex steroids across the menstrual cycle and lifespan has remained controversial, in part due to these limitations. We used validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) assays to determine testosterone (T) and dihydrotestosterone (DHT) along with estradiol (E2) and estrone (E1) levels across the menstrual cycle of 31 healthy premenopausal females and in 19 postmenopausal females. Samples were obtained in ovulatory women in the early follicular phase (EFP), midcycle and mid luteal phase (MLP). Overall, the levels of T, DHT, E2 and E1 in premenopausal women measured by LC-MS/MS were lower overall than previously reported with immunoassays. In premenopausal women, serum T, free T, E2, E1 and SHBG levels peaked at midcycle and remained higher in the MLP, whereas DHT did not change. In postmenopausal women, T, free T, SHBG and DHT were significantly lower than in premenopausal women, concomitant with declines in E2 and E1. These data support the hypothesis that the changes in T and DHT that occur across the cycle may reflect changes in SHBG and estrogen, whereas in menopause, androgen levels decrease. LC-MS/MS may provide more accurate and precise measurement of sex steroid hormones than prior immunoassay methods and can be useful to assess the clinical significance of changes in T, DHT, E2 and E1 levels in females.
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Circulating concentrations of androgen precursors DHEA and A4, as well as T and DHT, decline with age.
“These studies are of particular relevance to the impact of aging on fertility, as circulating concentrations of androgens precursors, such as DHEA and A4 as well as T and DHT decline with age [38,63].”
From Endometrial Intracrinology: Oestrogens, Androgens and Endometrial Disorders (2018) · cites this paper as [63]
The Introduction (page not provided) reports that testosterone declines with age in women, and the Discussion (page not provided) reports significantly lower DHT with menopause. The paper does not report an age-related decline in circulating DHEA or A4; its DHT finding concerns menopause rather than age independently. (LLM, conf=0.88)
Experimental — accuracy not yet measuredCirculating levels of estrogens vary greatly during the course of the menstrual cycle and decrease significantly in postmenopausal women.
“Circulating levels of estrogens vary greatly during the course of the menstrual cycle and decrease significantly in postmenopausal women (Table 3) [[306], [307], [308]].”
From Human steroid biosynthesis, metabolism and excretion are differentially reflected by serum and urine steroid metabolomes: a comprehensive review (2019) · cites this paper as [307]
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- [22]Shiraishi S Lee PW Leung A Goh VH Swerdloff RS Wang C Simultaneous measurement of serum testosterone and dihydrotestosterone by liquid chromatography-tandem mass spectrometry Clin Chem 54 11 1855 1863 18801940
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“These studies are of particular relevance to the impact of aging on fertility, as circulating concentrations of androgens precursors, such as DHEA and A4 as well as T and DHT decline with age [38,63].”
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- Authors
- Rothman, M. S., Carlson, N. E., Xu, M., Wang, C., Swerdloff, R., Lee, P., Goh, V. H. H., Ridgway, E. C., & Wierman, M. E.
- Affiliations
- University of Colorado Denver (US)
- The Lundquist Institute (US)
- Veterans Health Administration (US)
- Corresponding author
- Rothman, Micol S.
- ORCID
- Venue
- Steroids
- Publisher
- Elsevier BV
- Published
- 2011-01
- Volume
- 76
- Issue
- 1-2
- Pages
- 177-182
- ISSN
- 0039-128X (ISSN-L)
- PMC
- PMC3005029
- OpenAlex
- W2018452033
- Cited by
- 248
- References
- 48
- Citations by year
- 2026: 12 · 2025: 19 · 2024: 15 · 2023: 16 · 2022: 18 · 2021: 17 · 2020: 15 · 2019: 23 · 2018: 16 · 2017: 13 · 2016: 12 · 2015: 17 · 2014: 16 · 2013: 17 · 2012: 11
- FWCI
- 9.44
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Steroids (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Santen
- U.S. Public Health Service (M01 00425)
- National Center for Research Resources (M01RR000425)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD031191)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Health Sciences › Medicine › Reproductive Medicine › Ovarian function and disorders
- Keywords
- testosterone, dihydrotestosterone, estradiol, estrone, sex steroids, menstrual cycle, postmenopausal women, free testosterone, sex hormone-binding globulin, luteal phase, follicular phase, immunoassay comparison
- MeSH terms
- Adult, Aged, Chromatography, Liquid, Estradiol, Estrone, Female, Humans, Menstrual Cycle, Middle Aged, Reference Values, Dihydrotestosterone, Testosterone, Postmenopause, Tandem Mass Spectrometry, Young Adult
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