COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC:

Get the latest research information from NIH: Menu

Androgen for Leydig Cell Proliferation (ALCeP)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01206270
Recruitment Status : Completed
First Posted : September 21, 2010
Last Update Posted : September 25, 2018
Information provided by (Responsible Party):
Andrea M. Isidori, University of Roma La Sapienza

Brief Summary:
Patients with infertility often presents alterations at ultrasonographic examination of the testis. These alterations include a much higher incidence of small, multiple, non-palpable hypoechoic micro-nodules that can show internal vascularization. This finding often create alarm and anxiety, because it has to be placed in a differential diagnosis versus low-stage malignant germ cell tumors. Nevertheless, explorative surgery reveal that a consistent number of these lesion are benign, due to Leydig cell hyperplasia or Leydig cell tumours. The purpose of this study is to evaluate the effects of androgen therapy on the size and number of non-palpable hypoechoic micro-nodules in patients with elevated gonadotropin levels.

Condition or disease Intervention/treatment Phase
Klinefelter Syndrome Hypergonadotropic Hypogonadism Hypergonadotropic Azospermia Hypergonadotropic Cryptozoospermia Drug: Testosterone undecanoate Drug: Castor Oil Phase 2 Phase 3

Detailed Description:

Patients with the testicular dysgenesis syndrome, that comprises a variable spectrum of clinical manifestations, such as infertility, cryptorchidism, hypospadias, impaired spermatogenesis and testicular germ cell neoplasms, often develop alterations in the Leydig cell compartment. These alterations range from abnormal localization and clustering to hyperplasia or tumorous formation.

Leydig cell tumors (LCTs), although uncommon in the general population, are the most frequent non-germ cell testicular neoplasms, and their incidence has been reported increasingly growing, especially in infertile patients. Given that the focal areas of Leydig cell hyperplasia are nowadays easily detectable at ultrasonography of the testis (US), as small non-palpable hypoechoic micro-nodules that can show internal vascularization, their finding create a diagnostic challenge versus low-stage malignant germ cell tumors.

Patients with testicular dysgenesis syndrome in general exhibit an elevation of Follicle-Stimulating Hormone (FSH), but in these patients, very frequently, even Luteinizing Hormone (LH) is above the reference range. The latter can work as a growth factor for Leydig cells. Since exogenous testosterone can suppress LH levels, it could be that androgen therapy could revert the LH-induced growth stimulation of Leydig cell compartment.

The purpose of this study is to evaluate the effects of androgen therapy on the size and number of non-palpable hypoechoic micro-nodules in patients with elevated gonadotropin levels.

The purpose of this study is also to evaluate whether the behavior (UltraSonographic appearance, US) of the non-palpable hypoechoic micro-nodules during a 4-month trial of testosterone therapy can offer a novel diagnostic tool in the differential diagnosis of benign versus malignant testicular nodules.

The trial will be open only for patients with multiple non-palpable hypoechoic micro-nodules that have an elevation of both FSH and LH and that are not seeking conception.

Participants in the study will be randomized to one of two treatment groups, receiving either testosterone undecanoate (low-dose androgen) or placebo, for two 6 months. All participants will be evaluated for safety at the beginning of the study and at 2, 4, and 6 months with careful history, physical examination, blood sampling and testicular ultrasonography. Patients will also be offered the possibility to perform Magnetic Resonance Imaging (MRI) of the testis at baseline and after treatment, and/or surgical enucleation of the lesions.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 56 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Androgen Treatment in Leydig Cell Proliferation
Study Start Date : June 2009
Actual Primary Completion Date : June 2017
Actual Study Completion Date : June 2018

Arm Intervention/treatment
Experimental: Testosterone
Testosterone undecanoate 1000mg injection at baseline (0-week), 6-week, 18-week, 30-week
Drug: Testosterone undecanoate
Testosterone undecanoate 1000mg (in 4 ml of castor oil injections) at baseline (0-week), 6-week, 18-week, 30-week
Other Name: Nebido

Placebo Comparator: Placebo
Injection 4 ml of castor oil at baseline (week-0), week-6, week-18, week-30
Drug: Castor Oil
4 ml of Castor Oil injected at baseline (0-week), 6-week, 18-week, 30-week.

Primary Outcome Measures :
  1. Nodule Size per Number [ Time Frame: 4 month ]

    Percentage change of the area of the lesions multiplied by the number of the measured lesions: [(area_1 + area_2 + area_3 + ... + area_n)*n].

    The latter measure account for reduction in the number of lesions (disappearance).

Secondary Outcome Measures :
  1. Nodule Size [ Time Frame: 4 month ]
    Percentage change in the area of the lesion (measured with computer assisted graphics).

  2. Luteinizing Hormone (LH) [ Time Frame: 2 month ]
    Reduction of the serum Luteinizing Hormone (LH) levels during testosterone therapy

  3. Spermatogenesis [ Time Frame: 8 month (follow-up) ]
    Evaluation of sperm cell production after testosterone withdrawal.

  4. Testicular US echo-texture [ Time Frame: 36 month (follow-up) ]
    Changes in the number of areas / nodules / lesions in the long-term safety assessment

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Layout table for eligibility information
Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Non-palpable Multiple hypoechoic testicular nodules (with the largest having a diameter > 2 mm and < 12 mm)
  • Serum Follicle-stimulating hormone (FSH) > 7 mIU/ml (m-International-Unit/ml)
  • Serum Luteinizing hormone (LH) > 7 IU (International-Unit/ml)
  • Infertility: Klinefelter Syndrome, Hypergonadotropic Hypogonadism, Hypergonadotropic Azospermia, Hypergonadotropic Cryptozoospermia
  • negative testicular tumors markers: beta-hCG (Human chorionic gonadotropin), alpha-FP (alpha-Feto-Protein), CEA (Carcinoembryonic antigen), LDH (Lactate dehydrogenase), ferritin, PLAP (Placental Alkaline Phosphatase).

Exclusion Criteria:

  • Hypogonadotropic Hypogonadism
  • FSH o LH < 7 UI
  • non-homogeneous testicular lesion > 12 mm
  • positive testicular tumors markers: beta-hCG, alpha-FP, CEA, LDH, ferritin, PLAP
  • patients with contraindication to testosterone therapy: prostate cancer, PSA>4 ng/ml, severe hepatic or renal insufficiency, Hb>17, Htc>52%, severe urinary retention
  • desire to conceive
  • history of germ-cell testicular neoplasia

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01206270

Layout table for location information
Dipartimento di Fisiopatologia Medica
Rome, Lazio, Italy, 00161
Sponsors and Collaborators
University of Roma La Sapienza
Layout table for investigator information
Study Chair: Andrea Lenzi, MD Sapienza University of Rome
Principal Investigator: Andrea Isidori, MD, PhD Sapienza University of Rome
Study Director: Vincenzo Bonifacio, MD, PhD Sapienza University of Rome
Publications automatically indexed to this study by Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Andrea M. Isidori, Professor of Endocrinology, University of Roma La Sapienza Identifier: NCT01206270    
Other Study ID Numbers: 160/10
First Posted: September 21, 2010    Key Record Dates
Last Update Posted: September 25, 2018
Last Verified: September 2018
Keywords provided by Andrea M. Isidori, University of Roma La Sapienza:
Testicular Tumor
Additional relevant MeSH terms:
Layout table for MeSH terms
Klinefelter Syndrome
Gonadal Disorders
Endocrine System Diseases
Infertility, Male
Sex Chromosome Disorders of Sex Development
Disorders of Sex Development
Urogenital Abnormalities
Sex Chromosome Disorders
Chromosome Disorders
Congenital Abnormalities
Genetic Diseases, Inborn
Castor Oil
Testosterone undecanoate
Testosterone enanthate
Testosterone 17 beta-cypionate
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Anabolic Agents
Gastrointestinal Agents