The relationship between hypoprolactinemia and cardiometabolic health in women
Han, Thang S; Hannemann, Anke; Arffman, Riikka; Friedrich, Nele; Ittermann, Till; Wilkening, Robin; Piltonen, Terhi; Fry, Christopher Henry; Crujeiras, Ana B; Casanueva, Felipe F (2025-05-12)
Oxford University Press
12.05.2025
Han, T. S., Hannemann, A., Arffman, R., Friedrich, N., Ittermann, T., Wilkening, R., Piltonen, T., Fry, C. H., Crujeiras, A. B., & Casanueva, F. F. (2025). The relationship between hypoprolactinemia and cardiometabolic health in women. European Journal of Endocrinology, 192(5), 662–670. https://doi.org/10.1093/ejendo/lvaf101
https://creativecommons.org/licenses/by/4.0/
© The Author(s) 2025. Published by Oxford University Press on behalf of European Society of Endocrinology. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
https://creativecommons.org/licenses/by/4.0/
© The Author(s) 2025. Published by Oxford University Press on behalf of European Society of Endocrinology. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
https://creativecommons.org/licenses/by/4.0/
Julkaisun pysyvä osoite on
https://urn.fi/URN:NBN:fi:oulu-202505143408
https://urn.fi/URN:NBN:fi:oulu-202505143408
Tiivistelmä
Abstract
Background:
An evidence-based definition for the lower reference limit of serum prolactin (PRL) is lacking. We recently examined the European Male Ageing Study (EMAS) data and derive a threshold set at 3.0ng/ml for hypoprolactinemia in men. Here, we identified the lower reference limit for PRL in women.
Methods:
We used data from the Study of Health of Pomerania (SHIP-START, Germany, discovery cohort), and the Women’s Health Study (WENDY, Finland, validation cohort). The two-sigma empirical rule was applied to obtain a threshold at 2.5% of the log10 PRL distribution. Logistic and Cox regressions were used to examine the association between PRL and cardiometabolic outcomes at baseline and follow-up, respectively.
Results:
There were 2,048 women aged 20-81yr from SHIP-START and 1,730 women aged 33-37yr from WENDY. The low serum PRL threshold was derived at 2.60 ng/ml for premenopausal women and 2.29 ng/ml in women of all ages from SHIP-START, and 4.84ng/ml in WENDY. These thresholds were not far off from that previously identified in men (3ng/ml). In SHIP-START we further found that compared to PRL levels of 5.0-34.9ng/ml, lower PRL level were more commonly associated with type-2 diabetes and metabolic syndrome at baseline. Moreover, after a median of 12yr of follow-up (IQR=6.9-15.8yr), the risk of developing myocardial infarction was greater in women with PRL<2.30ng/ml (SHIP-START criteria): adjusted hazard ratio=4.19(95%CI:1.74-10.12), and in women with PRL<3ng/ml (EMAS criteria): hazard ratio=2.74(95%CI:1.44-5.21).
Conclusions:
Our data suggests that a serum PRL level lower than 3ng/ml could be adopted for identifying PRL-associated cardiometabolic disease in both sexes.
Background:
An evidence-based definition for the lower reference limit of serum prolactin (PRL) is lacking. We recently examined the European Male Ageing Study (EMAS) data and derive a threshold set at 3.0ng/ml for hypoprolactinemia in men. Here, we identified the lower reference limit for PRL in women.
Methods:
We used data from the Study of Health of Pomerania (SHIP-START, Germany, discovery cohort), and the Women’s Health Study (WENDY, Finland, validation cohort). The two-sigma empirical rule was applied to obtain a threshold at 2.5% of the log10 PRL distribution. Logistic and Cox regressions were used to examine the association between PRL and cardiometabolic outcomes at baseline and follow-up, respectively.
Results:
There were 2,048 women aged 20-81yr from SHIP-START and 1,730 women aged 33-37yr from WENDY. The low serum PRL threshold was derived at 2.60 ng/ml for premenopausal women and 2.29 ng/ml in women of all ages from SHIP-START, and 4.84ng/ml in WENDY. These thresholds were not far off from that previously identified in men (3ng/ml). In SHIP-START we further found that compared to PRL levels of 5.0-34.9ng/ml, lower PRL level were more commonly associated with type-2 diabetes and metabolic syndrome at baseline. Moreover, after a median of 12yr of follow-up (IQR=6.9-15.8yr), the risk of developing myocardial infarction was greater in women with PRL<2.30ng/ml (SHIP-START criteria): adjusted hazard ratio=4.19(95%CI:1.74-10.12), and in women with PRL<3ng/ml (EMAS criteria): hazard ratio=2.74(95%CI:1.44-5.21).
Conclusions:
Our data suggests that a serum PRL level lower than 3ng/ml could be adopted for identifying PRL-associated cardiometabolic disease in both sexes.
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