Leydig Cell Tumors

  • Author: Edmund S Sabanegh, Jr, MD; Chief Editor: Edward David Kim, MD, FACS  more...
Updated: Apr 17, 2015

Practice Essentials

Leydig cell tumors (see the image below) are rare testicular tumors of the male gonadal interstitium that may be hormonally active and lead to feminizing or virilizing syndromes.

Leydig cell tumors. Leydig cell tumors.

Signs and symptoms

Clinical manifestations include the following:

  • A nontender palpable testicular mass or nodule
  • Precocious puberty in prepubertal boys with androgen-secreting tumors
  • Feminizing symptoms in boys with estrogen-secreting tumors

Adults with androgen-secreting tumors are generally asymptomatic. Manifestations in adults with estrogen-secreting tumors include the following:

  • Loss of libido
  • Erectile dysfunction
  • Infertility
  • Gynecomastia
  • Feminine hair distribution
  • Gonadogenital atrophy

Leydig cell tumors may be an incidental finding of a testicular mass on scrotal ultrasonography performed for other conditions.

See Clinical Presentation for more detail.


Serum testosterone levels are usually elevated; however, serum estradiol levels may also be increased, especially when feminization is evident. Results of the following laboratory studies are normal in patients with pure Leydig cell tumors:

  • Serum alpha-fetoprotein
  • Beta human chorionic gonadotropin
  • Lactate dehydrogenase
  • Urine ketosteroids
  • Plasma cortisol
  • Adrenocorticotropic hormone stimulation test
  • Dexamethasone suppression test

Imaging studies

  • Scrotal ultrasonography: Confirms the diagnosis, especially when physical examination findings are equivocal [1, 2]
  • Magnetic resonance imaging: Can reveal small nonpalpable Leydig cell tumors that are not visible on ultrasonograms
  • CT scanning of the abdomen and chest radiography: Indicated if malignancy is suspected

See Workup for more detail.


Radical orchiectomy was once the primary treatment for Leydig cell tumors, and it remains in use for malignant cases. However, testis-sparing surgery with enucleation of the mass is increasingly being reported for benign cases.

When Leydig cell tumors are diagnosed and treated early, testicle-sparing surgery has proved to be a feasible and safe choice and could be regarded as first-line therapy. In a study of 20 patients with Leydig cell tumors who were treated with conservative surgery, follow-up for a mean of 15 years found 100% disease-free survival, with no local recurrences or metastases. Patients ranged in age from 5 to 61 years.[3]

See Treatment for more detail.



Leydig cell tumors are rare testicular tumors of the male gonadal interstitium. They are frequently hormonally active, leading to feminizing or virilizing syndromes.

Although uncommon, Leydig cell tumors comprise 1-3% of all testicular neoplasms. These tumors can be pure or can be mixed with other sex cord-stromal or germ cell tumors. Leydig cell tumors are usually benign, but malignant variants also occur.

Leydig cell tumors were once managed primarily with radical orchiectomy. However, the experience with conservative approaches has been growing, and enucleation has been used increasingly in both the adult and pediatric populations.[4]



A German anatomist, Franz Leydig, first described Leydig cells in 1870. Leydig cells are located within the interstitium of the testis, between the seminiferous tubules, and produce testosterone in response to luteinizing hormone. Through their hormonal balance, these cells play an important role in the development of secondary male characteristics and spermatogenesis.

The etiology of Leydig cell tumors remains unknown. Unlike germ cell testicular tumors, Leydig cell neoplasms are not associated with cryptorchidism. It is thought that an endocrine role may contribute to the development of these tumors. For example, an excessive stimulation of Leydig cells with luteinizing hormone due to a disorder of the hypothalamic-pituitary axis may induce their oncogenesis. Animal models have also demonstrated Leydig cell tumorigenesis following long-term estrogen administration.

Although these tumors usually secrete testosterone, the production of estrogen, progesterone, and corticosteroids has also been described. Estrogen excess and feminizing syndromes may occur from the peripheral aromatization of testosterone or from the direct production of estradiol by the tumor itself.




In the United States, Leydig cell testicular neoplasms are the most common sex cord-stromal tumors and comprise 1-3% of all testicular neoplasms. The tumors are most common in prepubertal boys aged 5-10 years and in adults aged 30-60 years. Approximately 10% of Leydig cell tumors are bilateral and 10% are malignant. However, Leydig cell tumors are always benign in children, as malignant variants have been reported only after puberty.


Leydig cell tumors are usually benign, but approximately 10% are malignant. The malignant variants occur only in adults.


Leydig cell tumors are most commonly found in males. Nonetheless, these tumors have been well-described in the ovarian stroma of females, who may present with signs and symptoms of virilization. Ovarian Leydig cell tumors are usually malignant, unlike Leydig cell tumors found in males.


Leydig cell tumors may occur in prepubertal boys but are most common in men aged 30-60 years.

Contributor Information and Disclosures

Edmund S Sabanegh, Jr, MD Chairman, Department of Urology, Glickman Urological and Kidney Institute, Cleveland Clinic Foundation

Edmund S Sabanegh, Jr, MD is a member of the following medical societies: American Medical Association, American Society of Andrology, Society of Reproductive Surgeons, Society for the Study of Male Reproduction, American Society for Reproductive Medicine, American Urological Association, SWOG

Disclosure: Nothing to disclose.


Anil A Thomas, MD Urologist, Department of Urology, Sunnybrook Medical Office,Kaiser Permanente

Anil A Thomas, MD is a member of the following medical societies: American Urological Association, Endourological Society, Society of Robotic Surgery

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Chief Editor

Edward David Kim, MD, FACS Professor of Surgery, Division of Urology, University of Tennessee Graduate School of Medicine; Consulting Staff, University of Tennessee Medical Center

Edward David Kim, MD, FACS is a member of the following medical societies: American College of Surgeons, Tennessee Medical Association, Sexual Medicine Society of North America, American Society for Reproductive Medicine, American Society of Andrology, American Urological Association

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Repros.

Additional Contributors

Erik T Goluboff, MD Professor, Department of Urology, College of Physicians and Surgeons, Columbia University College of Physicians and Surgeons; Director of Urology, Allen Pavilion, New York Presbyterian Hospital

Erik T Goluboff, MD is a member of the following medical societies: Alpha Omega Alpha, American Medical Association, American Urological Association, Medical Society of the State of New York, New York Academy of Medicine, Phi Beta Kappa, Society for Basic Urologic Research

Disclosure: Nothing to disclose.


Scott Rutchik, MD Assistant Professor, Department of Surgery, Division of Urology, University of Connecticut School of Medicine

Scott Rutchik, MD is a member of the following medical societies: American Urological Association

Disclosure: Nothing to disclose.

Dan Theodorescu, MD, PhD Paul A Bunn Professor of Cancer Research, Professor of Surgery and Pharmacology, Director, University of Colorado Comprehensive Cancer Center

Dan Theodorescu, MD, PhD is a member of the following medical societies: American Cancer Society, American College of Surgeons, American Urological Association, Medical Society of Virginia, Society for Basic Urologic Research, and Society of Urologic Oncology

Disclosure: Key Genomics Ownership interest Co-Founder-50% Stock Ownership; KromaTiD, Inc Stock Options Board membership

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Leydig cell tumors.
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