Gonadotropin-Releasing Hormone Deficiency in Adults Medication

Updated: Jan 09, 2017
  • Author: Vaishali Popat, MD, MPH; Chief Editor: Richard Scott Lucidi, MD, FACOG  more...
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Medication

Medication Summary

The goals of pharmacotherapy are to correct gonadal hormone deficiency and thereby reduce morbidity and prevent complications of hypogonadism.

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Hormones

Class Summary

These agents are used for replacement therapy in hypogonadism associated with a deficiency or absence of endogenous testosterone.

Testosterone (Depo-Testosterone, Delatestryl, Androderm, AndroGel, Testim)

Mainstay of treatment that is low-cost, safe, and effective. Dosage adjustments are made by monitoring trough levels prior to next injection. The goal is to maintain trough level in the low-normal range.

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Gonadotropins

Class Summary

These agents stimulate production of gonadal steroid hormones.

Human chorionic gonadotropin (Pregnyl, Novarel)

Spermatogenesis may be restored. In children, although doses should be based ultimately on clinical response and testosterone levels, a twice-weekly dosing regimen of 100-1500 U or 200-500 U on alternate days is typical. Advantages of hCG are normalization of testosterone levels and stimulation of testicular growth. Cost and numerous injections have led hCG to be reserved for those males attempting fertility.

Follicle-stimulating hormone (Follistim, Gonal-f)

Stimulates gonadal steroid production

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Gonadotropin-releasing hormones

Class Summary

The determination of which therapy to use gonadotropins or gonadotropin releasing hormone pulses is related more to preference than to science. Therapies appear to be equally effective. Time to full testicular growth and spermatogenesis may be somewhat shorter when using gonadotropin releasing hormone, although this appears controversial. Some anecdotal evidence suggests that gonadotropin releasing hormone therapy has proven successful in individuals refractory to gonadotropin treatments

Gonadorelin acetate (GnRH)

Stimulates pituitary release of luteinizing hormone. Two years of therapy may be required to reach maximal gonadal size and sperm production. Response time is influenced by initial testicular size; larger initial size yields less time on therapy. Once testis has reached 8 mL, regular semen analysis can be obtained. As with gonadotropins, dose and pulse are alternated based on testicular size, testosterone levels, spermatogenesis, and adverse effects.

Therapy in prepubertal boys may represent a more physiologic approach because the pulse of GnRH may be altered to mimic the natural process of puberty. The disadvantage of treatment, other than the need to use a pump, is that it is available at specialized centers only due to pending approval by FDA for this indication.

In females, this appears to be an effective method of stimulation of the ovary.

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Oral contraceptives

Class Summary

These agents may be used as hormone replacement therapy in women with IHH or KS; however, OCPs less closely mimic the physiologic menstrual cycle and thus are inferior to true hormone replacement therapy (eg, transdermal estradiol plus cyclic progesterone, see below). On the other hand, OCPs have the added advantage of contraception, if pregnancy is not desired, and they are more convenient to use. Importantly, OCPs should not be used in preadolescent girls with IHH and KS because a gradual exposure to estradiol is needed to induce secondary sexual characteristics, and early exposure to progestins results in abnormal breast development.

Ethinyl estradiol and norethindrone (Ovcon 35, Ovcon 50, Modicon)

In young females, low-dose PO contraception generally is an excellent method of hormone replacement. Any low-dose combination pill with 35 μg of ethinyl estradiol or less and any progestin is appropriate. Also useful because, on occasion, these women may spontaneously ovulate and become pregnant.

Conjugated equine estrogen and medroxyprogesterone (Prempro, Premphase)

Hormone replacement therapy that induces the synthesis of DNA, RNA, and various proteins in target tissues. Promotes development of secondary sex characteristics. Inhibits secretion of pituitary gonadotropins.

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Hormone Replacement Therapy

Class Summary

Physiologic hormone replacement therapy (HRT) most closely mimics the natural menstrual cycle by replacing (1) adequate levels of estradiol to maintain bone health and prevent symptoms of hypoestrogenemia (hot flashes, vaginal dryness, decreased libido) and (2) cyclic progesterone to induce withdrawal bleeding and thereby protect the endometrium in uterus-intact women. HRT can also be used in lower doses and without the progesterone component to induce secondary sexual characteristics in preadolescents with IHH and KS and primary amenorrhea.

Conjugated estrogens (Premarin)

Induces the synthesis of DNA, RNA, and various proteins in target tissues. Promotes development of secondary sex characteristics. Titrate dose depending on the hypoestrogenic symptoms

Estradiol (Climara, Estraderm, Estrace, Menostar)

Restores estrogen levels to concentrations that induce negative feedback at gonadotropic regulatory centers. Used for the purpose of hormone replacement and induction of puberty. Acts by regulating transcription of a limited number of genes. Estrogens diffuse through cell membranes, distribute themselves throughout the cell, and bind to and activate the nuclear estrogen receptor, a DNA-binding protein found in estrogen-responsive tissues. The activated estrogen receptor binds to specific DNA sequences or hormone-response elements, which enhances transcription of adjacent genes and, in turn, leads to the observed effects.

Continue treatment until breakthrough menstrual bleeding occurs and then initiate cyclical therapy. This can be achieved with any of a variety of PO contraceptives or the addition of medroxyprogesterone 10 mg to an estradiol regimen for 12 d every month.

Progesterone (Prometrium, Endometrin, Crinone)

Can be administered PO, vaginally, or IM. All routes of administration are equally effective. For inducing withdrawal bleeding in a woman in estrogen replacement, give daily for 12-14 d of each month. If pregnancy occurs, continue treatment for the first 10 wk of pregnancy.

Medroxyprogesterone acetate (Provera, Depo-Provera)

For inducing withdrawal bleeding in a woman in estrogen replacement, give daily for 12-14 d of each month.

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