Hypogonadism
Julie Adkins, Jill C. Cash, Mellisa A. Hall, Cheryl A. Glass, Angelito Tacderas, and Jenny Nelson Mullen
Definition
A.Hypogonadism in men is failure of the testis to produce physiological levels of testosterone and a normal number of spermatozoa.
Incidence
A.An estimated 38.7% of men older than 45 years of age have below-normal values of serum testosterone.
Pathogenesis
A.Hypogonadism in men can be the result of testicular dysfunction or nondevelopment (primary hypogonadism) or dysfunction of the pituitary or hypothalamus (secondary hypogonadism). The two clinical manifestations of impaired spermatogenesis are infertility and decreased testicular size. There are several possible clinical manifestations of testosterone deficiency, which are determined by its time of onset during reproductive development:
1.In utero first or second trimesters: Incomplete virilization of external genitalia, incomplete development of Wolffian ducts to form male internal genitalia.
2.Third trimester in utero: Micropenis.
3.Prepuberty: Incomplete pubertal maturation, eunuchoidal body habitus, poor muscle development, and reduced peak bone mass.
4.Postpuberty: Decreased energy, mood, and libido; decrease in sexual hair, hematocrit, muscle mass and strength, and bone mineral density.
Predisposing Factors
A.Hypogonadism associated with Klinefelter syndrome.
B.Chemotherapy.
C.Radiation therapy.
D.Excessive alcohol consumption.
E.Painful testicular swelling.
F.Anosmia associated with Kallmann syndrome.
G.Use of medications that cause hypogonadism: Ketoconazole or extended-release opiates.
Common Complaints
A.Decreased vigor and libido.
B.Depression.
Other Signs and Symptoms
A.Fatigue.
B.Difficulty concentrating.
C.Hot flashes.
D.No change in deepening of the voice.
E.Weight gain.
F.Signs of metabolic syndrome.
G.Erectile dysfunction.
Subjective Data
A.Interview the patient, inquiring about the history of known chromosomal abnormalities in the family or patient.
B.Ask about a history of cryptorchidism.
C.Is there any history of muscular weakness?
D.Is there a history of varicocele unresolved within 6 months of birth?
E.Inquire about known infections affecting the scrotum and testes.
F.Has the patient had therapeutic radiation to the area or a history of chemotherapy?
G.Ask about use of long-term ketoconazole, glucocorticoids, or long-acting opiates.
H.Any known testicular trauma?
I.Is there any history of known torsion?
J.Evaluate for a history of autoimmune disorders and/or chronic illnesses including cirrhosis, chronic renal failure, or HIV.
K.Has the patient noted a decrease in spontaneous erections?
Physical Examination
A.Inspect:
1.Testes for appropriate size.
2.Upper and lower body musculature.
3.Full/dense male-pattern beard.
4.Testes should be bilaterally descended.
5.Rule out eunuchoid appearance.
6.Breasts for gynecomastia.
7.Inspection findings less valuable following puberty as changes due to hypogonadism are obvious to inspection and take years to develop.
8.Penis for hypospadias.
B.Palpate:
1.The scrotum and testes for masses.
2.The breasts for masses (both male and females).
Diagnostic Tests
A.Serum testosterone (morning total), repeat to confirm.
B.Measurement of free testosterone if total testosterone is not near the lower limit.
C.Avoid lab tests during acute illness.
Differential Diagnoses
A.Hypogonadism.
B.Moderate obesity.
C.Nephrotic syndrome.
D.Hypothyroidism.
E.Use of glucocorticoids, progestins, and androgenic steroids.
F.Acromegaly.
G.Diabetes mellitus (DM).
H.Hepatic cirrhosis.
I.Hypopituitarism.
J.Malnutrition.
K.Klinefelter syndrome.
L.Depression.
M.Psychologic sexual dysfunction.
Plan
A.General interventions:
1.Testosterone replacement’s effect on reducing adverse health outcomes in the general population is unknown.
2.Testosterone levels vary significantly with circadian rhythms, illness, and medications.
3.Measurement of bone mineral density is recommended to assess fracture risk.
4.Luteinizing hormone (LH) and ESH concentrations can help distinguish between primary and secondary hypogonadism.
5.Differentials for secondary hypogonadism should evaluate for pituitary neoplasia, hyperprolactinemia, hemochromatosis, obstructive sleep apnea (OSA), and genetic disorders.
6.Testosterone replacement should be initiated only after a baseline prostate-specific antigen (PSA) and digital prostate exam. PSA levels should be followed routinely.
B.Patient teaching:
1.Both men and women with hypogonadism can lead normal lives with hormone replacement therapy.
2.Hormone replacement should continue throughout life.
3.Potential side effects of testosterone replacement therapy should be discussed prior to therapy.
4.Patients using topically absorbed testosterone gel or creams can transfer testosterone to female partners or children by direct skin-to-skin contact. Advise the patient to use caution with topical gels/creams.
C.Pharmaceutical therapy:
1.Injectable testosterone replacement.
2.1% testosterone gel: Androgel, Testim, Axiron.
3.Transdermal testosterone patch.
4.Buccal testosterone.
5.Implanted subcutaneous testosterone pellets.
6.Avoid testosterone therapy in the following patients:
Men who are planning fertility measures, breast/prostate cancer, elevated hematocrit, thrombophilia, severe multiple urinary tract infections (UTIs), untreated OSA, uncontrolled heart failure, and/or stroke/myocardial infarction (MI) within the last 6 months
Follow-Up
A.Patients receiving hormone replacement should be reevaluated every 6 months or more frequently.
B.Routine screening should be performed: Evaluate symptoms, adverse effects to testosterone therapy, adherence to regimen, hematocrit levels, cholesterol panel, and prostate function.
Consultation/Referral
A.Physician consultation prior to initiating testosterone therapy is advised.
B.Endocrinology referral is recommended for males not responsive to the replacement therapy.
C.Patients with primary hypogonadism should be referred to an endocrinologist for initial workup and management.
Individual Considerations
A.Geriatrics:
1.Current recommendations are not in favor of testosterone therapy for all older males. Providers should cautiously consider the benefits compared to the risks for older males. The benefits of testosterone replacement are unproven, and the long-term risks are unknown.
B.HIV patients:
1.Short-term testosterone replacement should be considered for HIV men with low testosterone, weight loss, and muscular wasting.