Treatment Overview

A diagnosis of hypogonadotropic hypogonadism (HH) can feel confusing and isolating, especially because it affects such personal aspects of development and health. For some, it means delayed puberty, watching peers grow while they feel left behind. For others diagnosed later in life, it may manifest as unexpected infertility, low energy, or a loss of sexual desire. These symptoms stem from a breakdown in communication between the brain and the reproductive organs. While the condition disrupts natural hormonal rhythms, it is highly responsive to treatment.

Treatment is vital not only to address immediate concerns like fertility or physical development but also to protect long-term health. Proper management supports bone density, muscle mass, and emotional well-being. Because the condition affects both men and women and can be diagnosed at different life stages, treatment plans are tailored to the individual. The choice of medication depends heavily on whether the immediate goal is to induce puberty, maintain secondary sex characteristics, or achieve pregnancy (National Institute of Child Health and Human Development, 2021).

Overview of treatment options for Hypogonadotropic Hypogonadism

The primary goal of treating HH is to replace the hormones the body is missing. Since the problem originates in the pituitary gland or hypothalamus failing to send signals, the ovaries or testes are usually healthy but dormant. Therefore, treatment focuses on either replacing the end-product hormones (testosterone or estrogen) or replacing the signaling hormones to “wake up” the reproductive organs.

For patients not currently seeking fertility, hormone replacement therapy is the standard approach. This maintains physical health and sexual function. For those wishing to conceive, the strategy shifts to using gonadotropins, medications that mimic the brain’s natural signals to stimulate sperm or egg production. This condition typically requires long-term management and monitoring by an endocrinologist.

Medications used for Hypogonadotropic Hypogonadism

For men and boys not seeking immediate fertility, testosterone replacement therapy (TRT) is the first-line treatment. This helps induce puberty or maintain adult male characteristics. Common forms include transdermal gels, skin patches, and intramuscular injections (such as testosterone cypionate or enanthate).

For women and girls, estrogen therapy is used to initiate puberty or maintain female characteristics. This is often prescribed as a pill or skin patch. Once estrogen levels are established, a progestin (like medroxyprogesterone) is added to the cycle to regulate menstrual periods and protect the uterine lining.

When fertility is the goal, doctors switch to gonadotropin therapy. For men, this typically involves human chorionic gonadotropin (hCG) injections to stimulate testosterone production within the testes, often combined with follicle-stimulating hormone (FSH) to maximize sperm production. For women, injections of FSH and luteinizing hormone (LH) substitutes are used to stimulate the ovaries to mature eggs. Clinical experience suggests that while hormone replacement provides quick symptom relief, fertility treatments often require several months to over a year to achieve success (Endocrine Society, 2022).

How these medications work

Hypothalamic Hypogonadism (HH) occurs when the brain fails to release the chemical messengers (GnRH, LH, FSH) needed to signal the testes or ovaries to produce sex hormones.

Hormone replacement therapies (Testosterone/Estrogen) treat HH by directly providing the missing sex hormones, supporting muscle, bone density, and libido, bypassing the signaling issue.

Gonadotropin injections, conversely, mimic the absent brain signals. hCG acts like LH, prompting the testes to produce testosterone. FSH stimulates sperm production in men or follicle maturation in women, essentially restoring the communication loop between the brain and reproductive system.

Side effects and safety considerations

Hormone therapies require monitoring for safety. Testosterone can cause acne, mood swings, increased red blood cells (thickening blood), or testicular shrinkage if used alone. Estrogen carries a small risk of blood clots, especially with smoking or prior clotting issues.

Potent Gonadotropin treatments for fertility risk ovarian hyperstimulation syndrome (OHSS) and higher chances of multiple pregnancies in women. Men may have breast tenderness or acne. Mandatory regular blood tests and ultrasounds (for fertility patients) ensure safe hormone levels. Patients must seek medical care for severe leg swelling, chest pain, or sudden severe abdominal pain.

Since everyone’s experience with the condition and its treatments can vary, working closely with a qualified healthcare provider helps ensure safe and effective care.

References

  1. National Institute of Child Health and Human Development. https://www.nichd.nih.gov
  2. Endocrine Society. https://www.endocrine.org
  3. Mayo Clinic. https://www.mayoclinic.org
  4. MedlinePlus. https://medlineplus.gov

Medications for Hypogonadotropic Hypogonadism

These are drugs that have been approved by the US Food and Drug Administration (FDA), meaning they have been determined to be safe and effective for use in Hypogonadotropic Hypogonadism.

Found 6 Approved Drugs for Hypogonadotropic Hypogonadism

Follitropin

Brand Names
Follistim, Gonal-f RFF Redi-ject, Gonal-f

Follitropin

Brand Names
Follistim, Gonal-f RFF Redi-ject, Gonal-f
Form: Injection, Kit
Method of administration: Subcutaneous
FDA approval date: March 24, 2004
Classification: Gonadotropin
Gonal-F is indicated for: GONAL-F is a gonadotropin indicated for: Women: Induction of ovulation and pregnancy in oligo-anovulatory infertile women for whom the cause of infertility is functional and not due to primary ovarian failure.

Undecanoate

Brand Names
Kyzatrex, Jatenzo, Tlando, Aveed

Undecanoate

Brand Names
Kyzatrex, Jatenzo, Tlando, Aveed
Form: Injection, Capsule
Method of administration: Oral, Intramuscular
FDA approval date: March 05, 2014
Classification: Androgen
TLANDO is indicated for testosterone replacement therapy in adult males for conditions associated with a deficiency or absence of endogenous testosterone: Primary hypogonadism (congenital or acquired): testicular failure due to conditions such as cryptorchidism, bilateral torsion, orchitis, vanishing testis syndrome, orchiectomy, Klinefelter's syndrome, chemotherapy, or toxic damage from alcohol or heavy metals. These men usually have low serum testosterone concentrations and gonadotropins (follicle stimulating hormone (FSH), luteinizing hormone (LH)) above the normal range [see Dosage and Administration.

Choriogonadotropin

Brand Names
Pregnyl, Ovidrel

Choriogonadotropin

Brand Names
Pregnyl, Ovidrel
Form: Injection, Kit
Method of administration: Subcutaneous
FDA approval date: October 06, 2003
Classification: Gonadotropin
Ovidrel ® PreFilled Syringe (choriogonadotropin alfa injection) is indicated for the induction of final follicular maturation and early luteinization in infertile women who have undergone pituitary desensitization and who have been appropriately pretreated with follicle stimulating hormones as part of an Assisted Reproductive Technology (ART) program such as in vitro fertilization and embryo transfer. Ovidrel ® PreFilled Syringe is also indicated for the induction of ovulation (OI) and pregnancy in anovulatory infertile patients in whom the cause of infertility is functional and not due to primary ovarian failure. Selection of Patients Before treatment with gonadotropins is instituted, a thorough gynecologic and endocrinologic evaluation must be performed. This should include an assessment of pelvic anatomy. Patients with tubal obstruction should receive Ovidrel ® PreFilled Syringe only if enrolled in an in vitro fertilization program. Primary ovarian failure should be excluded by the determination of gonadotropin levels. Appropriate evaluation should be performed to exclude pregnancy. Patients in later reproductive life have a greater predisposition to endometrial carcinoma as well as a higher incidence of anovulatory disorders. A thorough diagnostic evaluation should always be performed in patients who demonstrate abnormal uterine bleeding or other signs of endometrial abnormalities before starting FSH and Ovidrel ® PreFilled Syringe therapy. Evaluation of the partner's fertility potential should be included in the initial evaluation.

Xyosted

Generic Name
Enanthate

Xyosted

Generic Name
Enanthate
Form: Injection
Method of administration: Subcutaneous, Intramuscular
FDA approval date: September 18, 2012
Classification: Androgen
XYOSTED (testosterone enanthate) injection is an androgen indicated for testosterone replacement therapy in adult males for conditions associated with a deficiency or absence of endogenous testosterone. Primary hypogonadism (congenital or acquired): testicular failure due to cryptorchidism, bilateral torsion, orchitis, vanishing testis syndrome, orchiectomy, Klinefelter's syndrome, chemotherapy, or toxic damage from alcohol or heavy metals. These men usually have low serum testosterone concentrations and gonadotropins (follicle-stimulating hormone [FSH], luteinizing hormone [LH]) above the normal range. Hypogonadotropic hypogonadism (congenital or acquired): gonadotropin or luteinizing hormone-releasing hormone (LHRH) deficiency or pituitary-hypothalamic injury from tumors, trauma, or radiation. These men have low testosterone serum concentrations but have gonadotropins in the normal or low range. Limitations of Use: Safety and efficacy of XYOSTED in males less than 18 years old have not been established [see Use in Specific Populations.

Cypionate

Brand Names
Depo-Estradiol, Depo-Testosterone, Azmiro

Cypionate

Brand Names
Depo-Estradiol, Depo-Testosterone, Azmiro
Form: Injection, Kit
Method of administration: Intramuscular
FDA approval date: July 25, 1979
Classification: Androgen
Testosterone Cypionate Injection is indicated for replacement therapy in the male in conditions associated with symptoms of deficiency or absence of endogenous testosterone. Primary hypogonadism (congenital or acquired) - testicular failure due to cryptorchidism, bilateral torsion, orchitis, vanishing testis syndrome; or orchidectomy. Hypogonadotropic hypogonadism (congenital or acquired) - gonadotropin or LHRH deficiency, or pituitary-hypothalamic injury from tumors, trauma, or radiation. Safety and efficacy of Testosterone Cypionate Injection in men with “age­-related hypogonadism” (also referred to as “late-onset hypogonadism”) have not been established.
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