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Hypogonadism Clinical Presentation

  • Author: Stephen Kemp, MD, PhD; Chief Editor: George T Griffing, MD  more...
Updated: Jun 23, 2016


For both males and females with hypogonadism, determining whether evidence of a genital abnormality is present at birth or determining the timing and extent of puberty is important. In addition, because Kallmann syndrome (hypogonadotropic hypogonadism and anosmia [ie, lack of a sense of smell]) is a common cause of hypogonadotropic hypogonadism, inquiring about the sense of smell is important.

  • Males
    • Specific issues include the presence of developmental anomalies associated with the genital system (eg, hypospadias, micropenis, cryptorchidism). Guidelines for micropenis have been established.[1]
    • For postpubertal males, inquire about the rate of beard growth, libido and sexual function, muscle strength, and energy levels.
    • Investigate possible causes of acquired testicular failure (eg, mumps orchitis, trauma, radiation exposure of the head or testes, chemotherapy). Drugs that may interrupt testicular function include agents that interfere with testosterone synthesis, such as spironolactone, cyproterone, marijuana, heroin, and methadone.
  • Females
    • Ask about specific signs associated with Turner syndrome, such as lymphedema, cardiac or renal congenital anomalies, and short growth pattern.
    • Determine the age of menarche. Menstrual history is important in postpubertal females.


Physical findings may include the following:

  • Males
    • Evaluation of the testes is the most important feature of the physical examination. Determine whether both testes are palpable, their position in the scrotum, and their consistency. Testes size can be quantitated by comparison with testicular models (orchidometer), or their length and width may be measured. Before puberty, testes usually are 1-3 cm3 in volume (approximately 2 cm in length). During puberty, testes grow up to 25 cm3 in size.
    • Examining the genitalia for hypospadias is the next important step. Check the scrotum to see if it is completely fused. Finally, evaluate the extent of virilization.
    • Puberty should be staged using the Tanner criteria for genitalia, pubic hair, and axillary hair.
    • Look for signs of Klinefelter syndrome, such as tall stature (especially if legs are disproportionately long), gynecomastia, small or soft testes, and a eunuchoid body habitus.
  • Females
    • Examination of the genitalia is important.
    • Determine the extent of androgenization, which may be adrenal or ovarian in origin and is demonstrated in pubic and axillary hair.
    • Determine the extent of estrogenization, as evidenced by breast development and maturation of the vaginal mucosa.
    • Look for signs of Turner syndrome, such as short stature, webbing of the neck (eg, pterygium colli), a highly arched palate, short fourth metacarpals, widely spaced nipples, or multiple pigmented nevi.


The following causes of hypogonadism are noted:

Hypogonadotropic hypogonadism

See the image below.

Types of idiopathic hypogonadotropic hypogonadism.Types of idiopathic hypogonadotropic hypogonadism.

Causes of hyogonadotropic hypogonadism include the following:

  • CNS disorders
  • Tumors
  • Miscellaneous causes
    • Langerhans histiocytosis
    • Postinfectious lesions of the CNS
    • Vascular abnormalities of the CNS
    • Radiation therapy
    • Congenital malformations (especially associated with craniofacial anomalies)
    • Head trauma
  • Genetic causes (see Genetics of hypogonadotropic hypogonadism)
    • Kallmann syndrome (mutation in the KAL [anosmin] gene, as well as FGFR1, PROK2, and PROKR2), with hyposmia or anosmia or without anosmia
    • Mutations in GNRH1, KISS1R, GNRHR, TAC3, TACR3
    • Congenital adrenal hypoplasia (mutation in the DAX1 gene)
    • Mutations in the PROP1 and HESX1 genes
    • Mutations in the gene coding for the gonadotropin-releasing hormone (GnRH) receptor
    • Isolated luteinizing hormone (LH) deficiency
    • Isolated follicle-stimulating hormone (FSH) deficiency
  • Idiopathic and genetic forms of multiple hormone deficiencies
    • Chronic systemic disease and malnutrition
    • Exercise-induced amenorrhea
    • Miscellaneous disorders, including Prader-Willi syndrome, Laurence-Moon syndrome, Bardet-Biedl syndrome,[8]  functional gonadotropin deficiency (psychogenic amenorrhea, hypothyroidism, diabetes mellitus, Cushing syndrome), hyperprolactinemia, marijuana use, and Gaucher disease

Hypergonadotropic hypogonadism in males

  • Klinefelter syndrome
  • Inactivating mutations
    • LH beta subunit
    • FSH beta subunit
    • LH receptor
    • FSH receptor
  • Other causes of primary testicular failure
    • Chemotherapy
    • Radiation therapy
    • Testicular biosynthetic defects
    • Sertoli-cell-only syndrome
    • LH resistance
    • Anorchism and cryptorchidism

Hypergonadotropic hypogonadism in females

  • Turner syndrome
  • Inactivating mutations
    • LH beta subunit
    • FSH beta subunit
    • LH receptor
    • FSH receptor
  • XX and XY gonadal dysgenesis
    • Familial and sporadic XX gonadal dysgenesis and its variants
    • Familial and sporadic XY gonadal dysgenesis and its variants
  • Other causes of primary ovarian failure
    • Premature menopause
    • Radiation therapy
    • Chemotherapy
    • Autoimmune oophoritis
    • Resistant ovary
    • Galactosemia
    • Glycoprotein syndrome type 1
    • FSH-receptor gene mutations
    • LH/human chorionic gonadotropin (hCG) resistance
    • Polycystic ovarian disease
    • Noonan syndrome

Genetics of hypogonadotropic hypogonadism

To date, numerous genes have been identified as causes of hypogonadotropic hypogonadism. The genes include the following:

  • KAL is located on the X chromosome, just below the pseudoautosomal region. An abnormality in this gene results in Kallmann syndrome, which is characterized by anosmia and hypogonadotropic hypogonadism. FGFR1, FGF8, PROK2, and PROKR2 have also been associated with Kallmann syndrome. The relationship with Kallmann syndrome is thought to be due to the relation of these genes to the development and migration of gonadotropin-releasing hormone (GnRH) neurons.
  • The DAX1 gene is associated with X-linked adrenal hypoplasia congenita (hypogonadotropic hypogonadism and adrenal insufficiency).
  • GNRHR is the gene associated with the GnRH (LHRH) receptor.
  • GNRH1, KISS1R, and GNRHR genes have been associated with normosmic (sense of smell is not disrupted) hypogonadotropic hypogonadism.
  • TAC3 and TACR3 mutations have also been associated with normosmic hypogonadotropic hypogonadism, although their exact functions are unclear.
  • CHD7 mutation, which has been associated with CHARGE syndrome, has also been found in patients with both normosmic and anosmic hypogonadotropic hypogonadism.
  • PC1 is the gene for prohormone convertase 1. Abnormality of this gene causes hypogonadotropic hypogonadism and defects in prohormone processing.
  • In addition, mutations in the PROP1 gene have resulted in absence of several pituitary hormones, including growth hormone, thyroid-stimulating hormone, prolactin, and gonadotropins. PROP1 encodes a protein expressed in the embryonic pituitary, which is necessary for function of POU1F1 (formerly PIT1), which codes for a pituitary transcription factor.
  • In addition, mutation of the gene HESX1 has been associated with septooptic dysplasia, which may include poor development of the pituitary.
Contributor Information and Disclosures

Stephen Kemp, MD, PhD Former Professor, Department of Pediatrics, Section of Pediatric Endocrinology, University of Arkansas for Medical Sciences College of Medicine, Arkansas Children's Hospital

Stephen Kemp, MD, PhD is a member of the following medical societies: American Academy of Pediatrics, American Association of Clinical Endocrinologists, American Pediatric Society, Endocrine Society, Phi Beta Kappa, Southern Medical Association, Southern Society for Pediatric Research

Disclosure: Nothing to disclose.

Specialty Editor Board

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Barry B Bercu, MD Professor, Departments of Pediatrics, Molecular Pharmacology and Physiology, University of South Florida College of Medicine, All Children's Hospital

Barry B Bercu, MD is a member of the following medical societies: American Academy of Pediatrics, American Association of Clinical Endocrinologists, American Medical Association, American Pediatric Society, Association of Clinical Scientists, Endocrine Society, Florida Medical Association, Pediatric Endocrine Society, Society for Pediatric Research, Southern Society for Pediatric Research, Society for the Study of Reproduction, American Federation for Clinical Research, Pituitary Society

Disclosure: Nothing to disclose.

Chief Editor

George T Griffing, MD Professor Emeritus of Medicine, St Louis University School of Medicine

George T Griffing, MD is a member of the following medical societies: American Association for the Advancement of Science, International Society for Clinical Densitometry, Southern Society for Clinical Investigation, American College of Medical Practice Executives, American Association for Physician Leadership, American College of Physicians, American Diabetes Association, American Federation for Medical Research, American Heart Association, Central Society for Clinical and Translational Research, Endocrine Society

Disclosure: Nothing to disclose.

Additional Contributors

Bruce Buehler, MD Professor, Department of Pediatrics and Genetics, Director RSA, University of Nebraska Medical Center

Bruce Buehler, MD is a member of the following medical societies: American Academy for Cerebral Palsy and Developmental Medicine, American Academy of Pediatrics, American Association on Intellectual and Developmental Disabilities, American College of Medical Genetics and Genomics, American Association for Physician Leadership, American Medical Association, Nebraska Medical Association

Disclosure: Nothing to disclose.

Phyllis W Speiser, MD Chief, Division of Pediatric Endocrinology, Steven and Alexandra Cohen Children's Medical Center of New York; Professor of Pediatrics, Hofstra-North Shore LIJ School of Medicine at Hofstra University

Phyllis W Speiser, MD is a member of the following medical societies: American Association of Clinical Endocrinologists, Endocrine Society, Pediatric Endocrine Society, Society for Pediatric Research

Disclosure: Nothing to disclose.

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Types of idiopathic hypogonadotropic hypogonadism.
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