Physiopathology, Diagnosis, and Treatment of Secondary Female Hypogonadism

  • Athanasios Antoniou-Tsigkos
  • Djuro Macut
  • George Mastorakos
Reference work entry
Part of the Endocrinology book series (ENDOCR)


Female hypogonadism is a state characterized by absent or decreased ovarian function. It results from a gonadal (primary hypogonadism) or an extragonadal (secondary hypogonadism) princeps defect. In secondary hypogonadism, hypothalamic gonadotropin-releasing hormone or/and pituitary-secreted gonadotropins (follicle-stimulating hormone, luteinizing hormone) are either deficient or inactive leading to decreased secretion of gonadal steroids and subsequent amenorrhea. In certain conditions, both hypothalamic and pituitary dysfunctions are present. The genetic causes of secondary hypogonadism manifest mainly as congenital genetic syndromes (i.e., Kallmann syndrome) while some of them have been attributed to recognized single gene mutations and others have been characterized as idiopathic forms. Acquired causes of secondary hypogonadism include reversible causes such as functional hypothalamic amenorrhea, drugs, chronic illnesses, and irreversible causes such as central nervous system insults (trauma, irradiation, and intracranial tumors). Diagnosis should take in consideration the age at the clinical presentation (prepubertal or postpubertal), the physical findings as well as biochemical and imaging findings. Genetic investigation can be employed for more precise diagnosis. Finally, treatment should focus upon the treatment of the causal factor wherever possible and the hormone replacement therapy. The latter is adapted to the age of diagnosis of secondary female hypogonadism (prepubertal vs. postpubertal).


Secondary hypogonadism Hypogonadotropic hypogonadism Hypogonadism Kisspeptin Hypothalamic amenorrhea Kallman syndrome Idiopathic hypogonadotropic hypogonadism Hormone replacement therapy 

List of Abbreviations


Adrenocorticotropic hormone


Antidiuretic hormone


cyclic adenosine monophosphate


Antidiuretic hormone


Anti-Mullerian hormone


Human chorionic gonadotropin


Cognitive behavioral therapy


Constitutional delay of growth and puberty


Corticotropin-releasing hormone




Functional hypothalamic amenorrhea


Follicle-stimulating hormone


Gamma-Aminobutyric Acid


Gonadotropin-releasing hormone


Growth hormone




Isolated hypogonadotrophic hypogonadism


Insulin growth factor 1


Kisspeptin-Neurokinin B-Dynorphin


Kallmann syndrome


Low-density lipoprotein


Luteinizing hormone


α-Melanocyte-Stimulating hormone


Neuropeptide Y


Parathyroid hormone


paraventricular nucleus


Preoptic area






Sex hormone binding globulin


Thyroid stimulating hormone


Thyrotropin-releasing hormone


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Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Athanasios Antoniou-Tsigkos
    • 1
  • Djuro Macut
    • 2
  • George Mastorakos
    • 1
  1. 1.Endocrine Unit, ARETAIEION University HospitalNational and Kapodistrian University of AthensAthensGreece
  2. 2.Clinic of Endocrinology, Diabetes and Metabolic DiseasesUniversity of BelgradeBelgradeSerbia

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