eMedicine Specialties > Pediatrics: General Medicine > Endocrinology
Hypogonadism: Treatment & Medication
Updated: Jul 23, 2009
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Treatment
Medical Care
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 LHRH or 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 luteinizing hormone-releasing hormone (LHRH) or (more commonly) with a schedule of injections of human chorionic gonadotropin (hCG) and follicle-stimulating hormone (FSH).
- In patients with hypergonadotropic hypogonadism, fertility is not possible.
Surgical Care
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.
Consultations
- 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.
Medication
Treatment of patients with hypergonadotropic hypogonadism involves replacement of sex steroids in both males and females.
For treatment of patients with hypogonadotropic hypogonadism, the usual approach is replacement of sex steroids that initiate development and maintain secondary sex characteristics.
Sex steroid replacement does not result in increased testicular size in males or fertility in either males or females. Gonadotropin or GnRH replacement is offered to the patient when fertility is desired.
Many oral contraceptives can provide estrogen and progesterone in a combination that meets the replacement needs of the patient. Selection of a specific oral contraceptive agent needs to be individualized. All of the contraindications, cautions, and drug interactions for estrogens and progesterones apply, as listed in the tables below.
Testosterone agents
These agents are used for sex steroid replacement in males. All testosterone preparations are regulated as Schedule III controlled substances according to the Anabolic Steroids Control Act.
Testosterone (Andro-LA, Depo-Testosterone)
Several testosterone salts (eg, enanthate, cypionate) are available in a long-acting oil-based preparations. Promotes and maintains secondary sex characteristics in androgen-deficient males.
Adult
200-400 mg/mo IM; usually divided q2wk
Pediatric
Initial dose (to initiate puberty): 100 mg/mo IM
Can increase up to adult maintenance dose
Glucose metabolism altered with insulin; clotting factor metabolism altered with warfarin
Documented hypersensitivity; severe cardiac or renal disease; benign prostatic hypertrophy with obstruction; males with breast carcinoma; undiagnosed genital bleeding; for use only in males
Pregnancy
X - Contraindicated; benefit does not outweigh risk
Precautions
Too frequent or persistent penis erections; impaired liver or renal function
Testosterone patch (Androderm)
Recent addition to the options for testosterone replacement. Several preparations are available, including a scrotal patch (Testoderm) and several patches that may be applied at other sites (Testoderm TTS, Androderm). Patches are changed daily.
Adult
Topical patch: 2.5-6 mg/d
Pediatric
Initial dose: 2.5-6 mg/d; dose should start with topical patch that releases 2.5 mg/d in boys who have had minimal prior testosterone exposure; increase gradually to adult dose
Glucose metabolism altered with insulin; clotting factor metabolism altered with warfarin
Documented hypersensitivity; breast or prostate carcinoma; severe liver, renal, or cardiac disease; hypercalcemia; for use only in males
Pregnancy
X - Contraindicated; benefit does not outweigh risk
Precautions
Too frequent or persistent penis erections; impaired liver or renal function (seen less often with transcutaneous testosterone than with PO or parenteral preparations); monitor serum testosterone levels, growth, and bone age
Testosterone gel (AndroGel)
An androgenic anabolic steroid. The preparation topically is administered as gel.
Adult
5-10 g (delivers approximately 50-100 mg) applied topically every am to shoulders, upper arms, and abdomen
Pediatric
Not established
None reported
Documented hypersensitivity; breast or prostate carcinoma; female patients; boys <18 y; just after application, avoid direct contact with women who are pregnant
Pregnancy
X - Contraindicated; benefit does not outweigh risk
Precautions
Impaired liver function (seen less often with transcutaneous testosterone compared to oral or parenteral preparations); congestive heart failure; elderly patients; benign prostatic hypertrophy
Estrogen agents
These agents are used for sex steroid replacement in females.
Ethinyl estradiol (Estrace)
May initiate puberty in girls. A small unopposed dose (0.02 mg) is administered daily for 3-6 mo, then the dose is increased and cycled. After the first 6 mo, adding progestogen is often helpful.
Adult
0.02-0.1 mg/d PO alone for first 14-20 d of theoretical menstrual cycle, followed by 12-14 d of additional progesterone preparation
Pediatric
0.02-0.1 mg/d PO
May be administered unopposed initially; after 6-12 mo, should be administered alone for first 14-20 d of cycle, followed by addition of 12-14 d of progesterone
May reduce hypoprothrombinemic effects of anticoagulants; estrogen levels may be reduced with coadministration of barbiturates, rifampin, and other agents that induce hepatic microsomal enzymes; an increase in corticosteroid levels may occur when administered concurrently with ethinyl estradiol; use of ethinyl estradiol with hydantoins may cause spotting, breakthrough bleeding, and pregnancy; increase in fluid retention caused by estrogen intake may reduce seizure control
Documented hypersensitivity; known or suspected pregnancy; breast cancer; undiagnosed abnormal genital bleeding; active thrombophlebitis or thromboembolic disorders; history of thrombophlebitis, thrombosis, or thromboembolic disorders associated with previous estrogen use (except when used in treatment of breast or prostatic malignancy); for females only; smoking cigarettes
Pregnancy
X - Contraindicated; benefit does not outweigh risk
Precautions
Caution in hepatic impairment, migraine, seizure disorders, cerebrovascular disorders, breast cancer, or thromboembolic disease
Estradiol, transdermal (Climara, Vivelle, Esclim, Alora, FemPatch)
May initiate puberty in girls. Initially, a 0.05-mg patch may be applied 1-2 times/wk. After 6-12 mo, dose may be increased and cycled. After first 6 mo, adding progestogen is often helpful. A very low starting dose of estrogen is desired in young girls with bone ages at or below 12-13 y. Starting at higher doses may cause rapid epiphyseal maturation. If necessary, patches with a matrix-release mechanism (eg, Climara, Vivelle) may be cut to deliver a smaller dose. In the case of the Vivelle dot, half of the dot may be covered in order to lower the amount of estrogen absorbed.
Adult
Apply topical patch that delivers estradiol at rate of 0.025-0.1 mg/d; replace qwk or 2 times/wk according to specific patch directions
Pediatric
Administer as in adults; start with lowest dose
May reduce hypoprothrombinemic effect of anticoagulants; coadministration of barbiturates, rifampin, and other agents that induce hepatic microsomal enzymes may reduce estrogen levels; pharmacologic and toxicologic effects of corticosteroids may occur because of estrogen-induced inactivation of hepatic P-450 enzyme; loss of seizure control has been noted when administered concurrently with hydantoins
Documented hypersensitivity; known or suspected pregnancy; breast cancer; undiagnosed abnormal genital bleeding; active thrombophlebitis or thromboembolic disorders; history of thrombophlebitis, thrombosis, or thromboembolic disorders associated with previous estrogen use (except when used in treatment of breast or prostatic malignancy); for females only; smoking cigarettes
Pregnancy
X - Contraindicated; benefit does not outweigh risk
Precautions
Certain patients may develop undesirable manifestations of excessive estrogenic stimulation, such as abnormal or excessive uterine bleeding or mastodynia; estrogens may cause some degree of fluid retention (exercise caution); prolonged unopposed estrogen therapy may increase risk of endometrial hyperplasia
Conjugated estrogen (Premarin)
May initiate puberty in girls. A small unopposed dose is administered for 3-6 mo, then the dose is increased. After the first 6 mo, adding progestogen is often helpful.
Adult
0.625-1.25 mg/d PO
Pediatric
May be administered PO to initiate pubertal development in girls starting at lower dose (0.3 mg/d) and advancing to higher dose (0.625 mg/d)
When dose is increased, may add progesterone
After 1-2 y, may increase to adult dose (1.25 mg/d on days 1-21 of cycle)
May reduce hypoprothrombinemic effect of anticoagulants; coadministration of barbiturates, rifampin, and other agents that induce hepatic microsomal enzymes may reduce estrogen levels; pharmacologic and toxicologic effects of corticosteroids may occur because of estrogen-induced inactivation of hepatic P-450 enzyme; loss of seizure control has been noted when administered concurrently with hydantoins
Documented hypersensitivity; known or suspected pregnancy; breast cancer; undiagnosed abnormal genital bleeding; active thrombophlebitis or thromboembolic disorders; history of thrombophlebitis, thrombosis, or thromboembolic disorders associated with previous estrogen use (except when used in treatment of breast or prostatic malignancy); for females only; smoking cigarettes
Pregnancy
X - Contraindicated; benefit does not outweigh risk
Precautions
Certain patients may develop undesirable manifestations of excessive estrogenic stimulation, such as abnormal or excessive uterine bleeding or mastodynia; estrogens may cause some degree of fluid retention (exercise caution); prolonged unopposed estrogen therapy may increase risk of endometrial hyperplasia
Progesterone agents
These agents are added during the last 12-14 days of the menstrual cycle.
Norethindrone (Aygestin)
Transforms proliferative into secretory endometrium.
Adult
5 mg/d PO during final 12-14 d of menstrual cycle
Pediatric
Administer as in adults
Hepatic metabolism induced with aminoglutethimide or rifampin
Documented hypersensitivity; thromboembolic disorders; pregnancy; missed abortion; breast cancer; undiagnosed vaginal bleeding
Pregnancy
X - Contraindicated; benefit does not outweigh risk
Precautions
During lactation, impaired liver function, congestive heart failure, or hypertension; fluid retention, depression, glucose intolerance, and thromboembolic phenomena may occur; perform follow-up testing with Papanicolaou smears
Medroxyprogesterone (Provera, Amen, Cycrin)
Transforms proliferative into secretory endometrium.
Adult
5-10 mg/d PO during last 12-14 d of menstrual cycle
Pediatric
Administer as in adults
Hepatic metabolism induced with aminoglutethimide or rifampin
Documented hypersensitivity; cerebral apoplexy; undiagnosed vaginal bleeding; thrombophlebitis; liver dysfunction
Pregnancy
X - Contraindicated; benefit does not outweigh risk
Precautions
During lactation, impaired liver function, congestive heart failure, or hypertension; fluid retention, depression, glucose intolerance, and thromboembolic phenomena may occur; perform follow-up testing with Papanicolaou smears
More on Hypogonadism |
| Overview: Hypogonadism |
| Differential Diagnoses & Workup: Hypogonadism |
 Treatment & Medication: Hypogonadism |
| Follow-up: Hypogonadism |
| Multimedia: Hypogonadism |
| References |
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Further Reading
Keywords
hypogonadism, ovarian failure, testicular failure, gonadal failure, eunuchoidism, primary amenorrhea, secondary amenorrhea, decreased sexual function, sparse body hair, delayed epiphyseal closure, hypergonadotropic hypogonadism, hypogonadotropic hypogonadism, gonadotropin deficiency, Turner syndrome, Turner's syndrome, Klinefelter syndrome, Klinefelter's syndrome, infertility, sexual dysfunction, decreased muscular strength, primary hypogonadism, sexual ambiguity, Kallmann syndrome, Kallmann's syndrome, genital abnormality, hypospadias, cryptorchidism, micropenis, treatment, diagnosis
