Journal
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
Volume 107, Issue 7, Pages E3008-E3017Publisher
ENDOCRINE SOC
DOI: 10.1210/clinem/dgac150
Keywords
Anti-Mullerian hormone; combined oral contraception; dienogest; estradiol valerate; free androgen index; sex hormone binding globulin
Categories
Funding
- Swedish Cultural Foundation in Finland
- Helsinki University Hospital research funds
- Sigrid Juselius Foundation
- Finnish Medical Association
- Academy of Finland
- University of Oulu Graduate School
- Emil Aaltonen Foundation
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Limited studies have compared the effects of combined oral contraceptives (COCs) containing natural estrogens and synthetic ethinylestradiol (EE) on reproductive hormones. This study compared the effects of estradiol valerate (EV)+dienogest (DNG), EE+DNG, and DNG alone (active control) on levels of follicle stimulating hormone (FSH), luteinizing hormone, Anti-Mullerian hormone (AMH), ovarian steroids, sex hormone binding globulin (SHBG), and the Free Androgen Index (FAI). The results suggest that treatment with EV+DNG may have more beneficial health effects compared to EE+DNG.
Context There are limited studies comparing the effects of combined oral contraceptives (COCs) containing natural estrogens and synthetic ethinylestradiol (EE) on reproductive hormones. Objective To compare estradiol valerate (EV)+dienogest (DNG), EE+DNG, and DNG alone (an active control) on levels of follicle stimulating hormone (FSH), luteinizing hormone, Anti-Mullerian hormone (AMH), ovarian steroids, sex hormone binding globulin (SHBG), and the Free Androgen Index (FAI). Design Spin-off study from a randomized trial. Setting Outpatient setting at Helsinki and Oulu University Hospitals, Finland. Participants 59 healthy, 18-35-year-old ovulatory women were enrolled. Three women discontinued. The groups were comparable as regards age and body mass index. Interventions EV 2mg+DNG 2-3mg (n=20), EE 0.03mg+DNG 2mg (n=20) and DNG 2mg (n=19) were used continuously for nine weeks. Blood samples were drawn at baseline, and at 5 and 9 weeks. Main Outcome Measures EV+DNG suppressed FSH by -27% (-51:-3) (median [95%CI]) vs. EE+DNG, -64% (-78: -51), P=0.04, but AMH levels decreased similarly by -9% (-18: -0.1) vs. -13% (-28:0.2), P=0.38, respectively. EV+DNG increased SHBG levels by 56% (30:82) and EE+DNG by 385% (313:423), P<0.001. Total testosterone (T) decreased by 16% (-27: -5) in the EV+DNG group but it did not decrease in the EE+DNG group, whereas the FAI decreased by -39% (-54: -25) vs. -72% (-78: -67), PConclusions Compared with EE+DNG, treatment with EV+DNG resulted in milder pituitary downregulation and reduced induction of hepatic SHBG synthesis-potentially carrying more beneficial health effects.
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