Meyahealth
HomeGeneticsConditionLeydig cell hypoplasia
Back to Condition
Leydig cell hypoplasia
Reviewed by Medicinsk Expert•Last updated: 2026-10-22•Condition

Leydig Cell Hypoplasia

Leydig cell hypoplasia is a rare genetic condition that impairs male sexual development by preventing the proper development of hormone-producing Leydig cells. This results in a range of genital abnormalities, from ambiguous genitalia to completely female external structures in genetically male individuals.

Overview

Leydig cell hypoplasia is a condition that affects male sexual development. It is characterized by underdevelopment (hypoplasia) of Leydig cells in the testes. Leydig cells secrete male sex hormones (androgens) that are important for normal male sexual development before birth and during puberty.

Symptoms and Clinical Features

In Leydig cell hypoplasia, affected individuals with a typical male chromosomal pattern (46,XY) may experience a range of genital abnormalities. Because of these abnormalities, the external genitalia may not look clearly male or clearly female. Common features include:

  • A small penis (micropenis)
  • The opening of the urethra on the underside of the penis (hypospadias)
  • A scrotum divided into two lobes (bifid scrotum)

Severe Cases (Type 1) vs. Milder Cases (Type 2)

In more severe cases of Leydig cell hypoplasia (often referred to as type 1), individuals with a 46,XY chromosomal pattern are born with female external genitalia. They have small, undescended testes located abnormally in the pelvis, abdomen, or groin. These individuals do not develop secondary sex characteristics, such as increased body hair, at puberty. Less severe cases are designated as type 2.

Frequency

Leydig cell hypoplasia is a rare disorder; its prevalence is currently unknown.

Causes

Mutations in the LHCGR gene cause Leydig cell hypoplasia. The LHCGR gene provides instructions for making a protein called the luteinizing hormone/chorionic gonadotropin receptor. This receptor protein allows the body to respond appropriately to two specific ligands: luteinizing hormone and chorionic gonadotropin.

In males, chorionic gonadotropin stimulates the development of Leydig cells in the testes, and luteinizing hormone triggers these cells to produce androgens, including testosterone. Testosterone controls male sexual development and reproduction. In females, luteinizing hormone triggers ovulation, and chorionic gonadotropin helps maintain pregnancy.

The LHCGR gene mutations that cause Leydig cell hypoplasia disrupt receptor function, impeding the body's ability to react to these hormones. In males, this results in poorly developed or absent Leydig cells and impaired production of testosterone. This lack of testosterone interferes with the development of male reproductive organs before birth and the changes that normally appear at puberty. Mutations that completely prevent the production of any functional receptor protein cause the severe features of the disorder, while mutations that allow some receptor function cause milder signs and symptoms.

Inheritance

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

Only individuals who are genetically male (with one X and one Y chromosome in each cell) and have mutations in both copies of the LHCGR gene display the characteristic signs of Leydig cell hypoplasia.

Genetically female individuals (with two X chromosomes in each cell) may inherit mutations in both copies of the LHCGR gene, but they do not develop Leydig cell hypoplasia because they do not have Leydig cells. They have normal female genitalia and normal breast and pubic hair development, but they may experience:

  • Delayed menstruation (beginning after age 16)
  • Irregular menstrual periods
  • Inability to have children (infertility) due to a lack of ovulation

Other Names for This Condition

  • 46,XY disorder of sex development due to LH defects
  • LCH
  • Leydig cell agenesis
  • LH resistance due to LH receptor deactivation
  • Male hypergonadotropic hypogonadism due to LHCGR defect

Frequently Asked Questions

Untreated hypogonadism leads to progressive osteoporosis, increased fracture risk, loss of lean body mass, reduced libido, fatigue, and metabolic disturbances such as insulin resistance and dyslipidemia. Regular bone density monitoring and lifelong testosterone therapy are recommended to mitigate these risks.
Low‑dose testosterone gel or intramuscular injections are typically begun around 12–14 years of age, mimicking the natural rise of testosterone. The regimen is gradually increased over 2–3 years to achieve adult male levels, supporting virilization, growth of muscle mass, and bone mineralization.
Spermatogenesis is usually absent because the testes lack functional Leydig cells, but in milder type 2 cases focal Leydig tissue may produce sperm. Testicular sperm extraction (TESE) combined with intracytoplasmic sperm injection (ICSI) can be attempted; otherwise donor sperm or adoption are alternatives.
Diagnosis usually combines a serum hormone panel (low testosterone with normal or elevated LH/FSH), pelvic ultrasound to locate undescended testes, and definitive confirmation by molecular genetic testing for pathogenic variants in the LHCGR gene.
Source: MedlinePlus, National Library of Medicine

MedlinePlus brings together authoritative health information from the National Library of Medicine (NLM), the National Institutes of Health (NIH), and other government agencies and health-related organizations.

Meyahealth

Ⓒ 2026. All rights reserved by MEYA

About UsTerms & PolicyFAQ