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Reproductive Biology and Endocrinology
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Reproductive Biology and Endocrinology
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The importance of adrenal hypoandrogenism in infertile women with low functional ovarian reserve: a case study of associated adrenal insufficiency

Authors: Gleicher, Norbert; Kushnir, Vitaly A.; Weghofer, Andrea; Barad, David H.;

The importance of adrenal hypoandrogenism in infertile women with low functional ovarian reserve: a case study of associated adrenal insufficiency

Abstract

Low testosterone (T), whether due to ovarian and/or adrenal insufficiency, usually results in poor follicle maturation at small growing follicle stages. The consequence is a phenotype of low functional ovarian reserve (LFOR), characterized by poor granulosa cell mass, low anti-Müllerian hormone and estradiol but rising follicle stimulating hormone. Such hypoandrogenism can be of ovarian and/or adrenal origin. Dehydroepiandrosterone sulfate (DHEAS) is exclusively produced by adrenals and, therefore, reflects adrenal androgen production in the zona reticularis. We here determined in a case study of infertile women with LFOR the presence of adrenal hypoandrogenism, its effects on ovarian function, and the possibility of presence of concomitant adrenal insufficiency (AI), thus reflecting insufficiency of all three adrenal cortical zonae.We searched our center's anonymized electronic research database for women with LFOR, who were also characterized by peripheral adrenal hypoandrogenemia (total testosterone < 16.9 ng/dL) and low DHEAS (<76.0 μg/dL). Among 225 women with LFOR, we identified 29 (12.9 %). The adrenal function of so identified women were further investigated with morning cortisol and ACTH levels and/or standard ACTH stimulation tests. We also determined the prevalence of classical AI (insufficiency glucocorticoid production by zona fasciculata) in hypoandrogenic women with LFOR, and impact of adrenal hypoandrogenism on ovaries.Among 14/28 women with adrenal hypoandrogenism due to insufficiency of the zona reticularis available for follow up, 4 (28.6 %) also demonstrated previously unrecognized classical primary, secondary or tertiary AI due to insufficiency of the zona fasciculata. An additional patient with presenting diagnosis of seemingly primary ovarian insufficiency (POI), demonstrated extremely low T and DHEAS levels, a diagnosis of Addison's disease, and was on glucocorticoid but not androgen supplementation. As her dramatic improvement in ovarian function criteria after androgen supplementation confirmed, her correct diagnosis, therefore, was actually secondary ovarian insufficiency (SOI) due to adrenal hypoandrogenism.Women with LFOR, characterized by low T and DHEAS, are also at risk for AI, while women with AI may be at risk for adrenal induced hypoandrogenism and, therefore, SOI. A currently undetermined percentage of POI patients actually are, likely, affected by SOI, a for prognostic reasons highly significant difference in diagnosis.

Keywords

Adult, Research, Primary Ovarian Insufficiency, Diagnosis, Differential, Endocrinology, Reproductive Medicine, Humans, Female, Ovarian Reserve, Infertility, Female, Developmental Biology, Adrenal Insufficiency, Retrospective Studies

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citations
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
21
Top 10%
Top 10%
Top 10%
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