Hypogonadism Treatment & Management
- Author: Stephen Kemp, MD, PhD; Chief Editor: George T Griffing, MD more...
In prepubertal patients with hypogonadism, treatment is directed at initiating pubertal development at the appropriate age. All such treatment is hormonal replacement therapy. Although the simplest and most successful treatment for both males and females with either hypergonadotropic or hypogonadotrophic hypogonadism is replacement of sex steroids, in hypogonadotropic hypogonadism, the therapy does not confer fertility or, in men, stimulate testicular growth.
An alternative for men with hypogonadotropic hypogonadism has been treatment with pulsatile luteinizing hormone-releasing hormone (LHRH) or human chorionic gonadotropin (hCG), either of which can stimulate testicular growth. Because such treatment is more complex than testosterone replacement, and because treatment with testosterone does not interfere with later therapy to induce fertility, most male patients with hypogonadotropic hypogonadism prefer to initiate and maintain virilization with testosterone.
At a time when fertility is desired, it may be induced with either pulsatile LHRH or (more commonly) with a schedule of injections of hCG and follicle-stimulating hormone (FSH).
A nasal testosterone replacement therapy has been approved by the US Food and Drug Administration (FDA) for adult males with conditions such as primary hypogonadism (congenital or acquired) and hypogonadotropic hypogonadism (congenital or acquired) resulting from a deficiency or absence of endogenous testosterone. The recommended dosage is 33 mg/day in three divided doses. The drug has not been approved for males younger than 18 years.
A review by the Pharmacovigilance Risk Assessment Committee (PRAC) of the European Medicines Agency (EMA) found that the evidence concerning the risk of serious cardiovascular side effects from the use of testosterone in men with hypogonadism was inconsistent.[10, 11] The PRAC determined that the benefits of testosterone outweigh its risks but stressed that testosterone-containing medicines should be used only where lack of testosterone has been confirmed by signs and symptoms, as well as by laboratory tests.
However, a literature review by Albert and Morley indicated that testosterone supplementation in males aged 65 years or older may increase the risk of cardiovascular events, particularly during the first year of treatment. However, intramuscular testosterone seemed to carry less risk than other forms.
In patients with hypergonadotropic hypogonadism, fertility is not possible.
The only issue of surgical relevance is whether gonadal tissue should be removed.
Because of the significant risk of gonadoblastoma and carcinoma, gonadal tissue should be removed in females with karyotypes containing a Y chromosome. This situation is observed in females with XY gonadal dysgenesis or in patients with Turner syndrome who have a karyotype that contains a Y chromosome (usually in 1 of 2 or more mosaic karyotypes). Males with nonfunctioning testicular tissue should undergo orchiectomy and replacement with prostheses.
Consultation with a reproductive endocrinologist is required for patients who would like to become fertile.
Administration of pulsatile LHRH in adolescents before fertility is desired carries no benefit.
In men, complications of untreated hypogonadism include loss of libido, failure to achieve physical strength, the social implications of failing to go through puberty with peers (if hypogonadism occurs before puberty), and osteoporosis. In addition, if hypogonadism occurs before epiphyseal closure, the result is usually tall stature with a eunuchoid body habitus. Even treated males with primary hypogonadism are infertile. However, men who have hypogonadism due to hypothalamic or pituitary dysfunction can potentially become fertile with administration of gonadotropins.
A retrospective study by Baillargeon et al indicated that males with untreated hypogonadism are at increased risk for the development of any rheumatic autoimmune disease, as well as for rheumatoid arthritis and lupus.
In women with hypogonadism, complications include the social implication of failing to go through puberty with peers (if hypogonadism occurs before puberty). An additional concern for untreated women is osteoporosis, which can be avoided with estrogen replacement. Women who have hypogonadism because of hypothalamic or pituitary dysfunction can potentially become fertile with administration of gonadotropins. Women with primary hypogonadism are infertile; however, with in vitro fertilization using a donor ovum, these women can carry an infant to term.
Osteoporosis has an earlier onset in individuals with hypogonadism; hence, bone mineral density should be compared with age-matched normative standards, and followed longitudinally. Prescribe treatment using appropriate therapeutic interventions.
Reevaluate patients with hypogonadism receiving hormone replacement therapy every 6-12 months.
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