Effect of four different oral contraceptives on various sex hormones and serum-binding globulins
Abstract
In a double-blind, controlled, randomized, four-arm, bicentric clinical study, the effect of four oral contraceptives (OCs) on various hormone parameters and serum-binding globulins was investigated. Four groups with 25 volunteers each (18-35 years of age) were treated for six cycles with monophasic combinations containing 21 tablets with either 30 microg ethinylestradiol (EE) + 2 mg dienogest (DNG) (30EE/DNG), 20 microg EE + 2 mg DNG (20EE/DNG), 10 microg EE + 2 mg estradiol valerate (EV) + 2 mg DNG (EE/EV/DNG) or 20 microg EE + 100 microg levonorgestrel (LNG) (EE/LNG). The study was completed by 91 subjects. Blood samples were taken after at least 12 h of fasting on Day 21-26 of the preceding control cycle and on Day 18-21 of the first, third and sixth treatment cycle. The serum concentrations of free testosterone were significantly decreased by about 40-60% in all four groups, while those of dehydroepiandrosterone sulfate (DHEAS) showed a time-dependent decrease during treatment. Except for EE/EV/DNG, which increased prolactin significantly during the third and sixth cycles, no change was observed with the EE-containing preparations. There was a significant increase in the levels of serum-binding globulins during treatment, which differed according to the composition of the OCs used. The rise in sex hormone-binding globulin (SHBG) was highest during intake of 30EE/DNG (+320%) and lowest with EE/LNG (+80%), while the effect of 20EE/DNG and EE/EV/DNG was similar (+270%). The thyroxine-binding globulin (TBG) levels increased significantly, by 50-60%, during treatment with the DNG-containing formulations, while the effect of EE/LNG was less significant (+30%). The rise in corticosteroid-binding globulin (CBG), which occurred in all groups, was most pronounced in women treated with 30EE/DNG (+90%) and least with EE/EV/DNG (+55%), indicating a strong influence of EE and no effect of the progestogen component. In all treatment groups, the frequency of intracyclic bleeding rose in the first treatment cycle and decreased thereafter. Cycle control was significantly better with 30EE/DNG or EE/LNG than with 20EE/DNG or EE/EV/DNG. There was no significant change in blood pressure, body mass index or pulse rate throughout the study. In conclusion, the DNG-containing OCs caused a higher rise in SHBG and TBG levels than the LNG-containing preparation. The effects on CBG suggest a lesser hepatic effect of 2 mg EV as compared to 20 or 30 microg EE. In contrast to EE, the use of estradiol in OCs appeared to increase prolactin release, while the cycle control was better with the OC containing 30 microg EE.
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In the liver, combined oral contraceptives stimulate the synthesis of steroid-binding globulins, such as sex hormone-binding globulin (SHBG), thereby affecting circulating free steroid levels.
“In the liver, COCs stimulate the synthesis of steroid-binding globulins, such as sex hormone-binding globulin (SHBG), thereby affecting circulating, free steroid levels”
From Ethinylestradiol in combined hormonal contraceptive has a broader effect on serum proteome compared with estradiol valerate: a randomized controlled trial (2023) · cites this paper as Wiegratz et al., 2003
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- Authors
- Wiegratz, I., Kutschera, E., Lee, J. H., Moore, C., Mellinger, U., Winkler, U. H., & Kuhl, H.
- Affiliations
- Goethe University Frankfurt (DE)
- Venue
- Contraception
- Publisher
- Elsevier BV
- Published
- 2003-01
- Volume
- 67
- Issue
- 1
- Pages
- 25-32
- ISSN
- 0010-7824 (ISSN-L)
- OpenAlex
- W2002526921
- Cited by
- 239
- References
- 40
- Citations by year
- 2026: 6 · 2025: 10 · 2024: 10 · 2023: 10 · 2022: 12 · 2021: 10 · 2020: 13 · 2019: 14 · 2018: 9 · 2017: 8 · 2016: 13 · 2015: 13 · 2014: 10 · 2013: 12 · 2012: 13
- FWCI
- 7.11
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Contraception (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Reproductive Health and Contraception
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Health Sciences › Medicine › Reproductive Medicine › Ovarian function and disorders
- Keywords
- oral contraceptives, sex hormones, sex hormone-binding globulin, ethinyl estradiol, dienogest, estradiol valerate, levonorgestrel, free testosterone, dehydroepiandrosterone sulfate, prolactin, thyroxine-binding globulin, corticosteroid-binding globulin
- MeSH terms
- Adolescent, Adult, Contraceptives, Oral, Double-Blind Method, Estradiol, Ethinyl Estradiol, Female, Humans, Nandrolone, Reference Values, Sex Hormone-Binding Globulin, Gonadal Steroid Hormones, Testosterone, Thyroxine-Binding Proteins, Treatment Outcome, Levonorgestrel, Dehydroepiandrosterone Sulfate
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