Hypogonadism in Men and Women

What hypogonadism is

The gonads (testes and ovaries) have two jobs: making sex hormones and making sperm or eggs. They are controlled by a chain of signals:

1. The hypothalamus in the brain releases GnRH in pulses.
2. GnRH tells the pituitary gland to release LH and FSH.
3. LH and FSH stimulate the testes to make testosterone and sperm, or the ovaries to make estrogen and progesterone and mature eggs.

Hypogonadism happens when any link in this chain breaks. Where it breaks determines the type and the treatment.

Primary vs secondary hypogonadism

Causes

Primary hypogonadism

• Klinefelter syndrome (47,XXY): the most common genetic cause in men.
• Turner syndrome: loss of all or part of one X chromosome in women, causing early ovarian failure.
• Primary ovarian insufficiency: ovaries stop working normally before age 40, from autoimmune, genetic (such as fragile X premutation) or unknown causes.
• Chemotherapy and radiation to the pelvis or testes.
• Testicular injury, torsion or surgery, and undescended testes.
• Mumps orchitis after puberty.
• Hemochromatosis (iron overload), which can affect the testes and pituitary.

Secondary hypogonadism

• Pituitary tumors and their treatment, including prolactin-secreting adenomas. High prolactin from any cause suppresses GnRH.
• Kallmann syndrome: a genetic condition with absent puberty and loss of smell.
• Medicines: long-term opioids, anabolic steroids and testosterone taken without medical supervision, high-dose steroids and GnRH-blocking drugs.
• Obesity, type 2 diabetes and obstructive sleep apnea, very common causes of low testosterone in men.
• Low energy availability: extreme exercise, low body weight or eating disorders, causing hypothalamic amenorrhea in women.
• Serious illness, head injury, brain radiation, and infiltrative diseases such as sarcoidosis.

Age-related decline in testosterone in men is gradual and modest. It is sometimes called late-onset hypogonadism and is often linked to weight and other health problems.

Symptoms

Symptoms depend on age at onset and sex.

Before puberty

• delayed or absent puberty
• in boys: little growth of the penis and testes, high voice, little body hair, long arms and legs
• in girls: no breast development or periods

In men

• low sex drive and erectile dysfunction, fewer morning erections
• fatigue, low mood and poor concentration
• reduced muscle mass and strength, more body fat
• loss of body and facial hair, smaller or softer testes
• breast enlargement (gynecomastia)
• hot flashes and sweats in severe cases
• low sperm count and infertility
• bone thinning and fractures

In women

• irregular or absent periods (amenorrhea)
• hot flashes, night sweats and vaginal dryness
• low sex drive and pain with intercourse
• infertility
• bone loss and an earlier rise in heart risk

Diagnosis

• Morning total testosterone (men), measured fasting between about 7 and 10 a.m., and repeated, because levels vary and dip after meals or illness. The AUA uses a cut-off of 300 ng/dL. Free testosterone may be checked when binding protein levels are abnormal.
• Estradiol (women), interpreted with the menstrual cycle.
• LH and FSH to separate primary from secondary.
• Prolactin, thyroid tests and iron studies.
• Semen analysis if fertility matters.
• Karyotype (chromosome test) if Klinefelter or Turner syndrome is suspected.
• Pituitary MRI if secondary hypogonadism is unexplained, prolactin is high or there are headaches or vision changes.
• Bone density scan (DEXA) to check for osteoporosis.

Treatment

Treat the cause

Stopping opioids or anabolic steroids where possible, weight loss, treating sleep apnea, treating a prolactinoma with cabergoline, or removing a pituitary tumor can restore hormone levels in secondary hypogonadism.

Testosterone replacement in men

Testosterone is given as gels, injections, patches, pellets, nasal or oral forms. It improves sex drive, energy, muscle and bone. Monitoring includes testosterone levels, hematocrit (testosterone can thicken the blood) and prostate checks in older men.

Estrogen replacement in women

Estrogen with a progestogen (to protect the womb lining if the uterus is present) relieves symptoms and protects bones and heart. Young women with POI or Turner syndrome are usually advised to take it until about the natural age of menopause, around 51. Combined birth control pills are an alternative for some.

Puberty induction

Teenagers receive low doses of testosterone or estrogen that are increased gradually over 2 to 3 years to mimic natural puberty.

Fertility treatment

• Secondary hypogonadism: pulsatile GnRH or injections of hCG and FSH can trigger sperm production or ovulation.
• Primary hypogonadism: sperm retrieval from the testes with IVF and ICSI is possible in some men with Klinefelter syndrome. Women with ovarian failure can often conceive with donor eggs.

Complications and outlook

Untreated hypogonadism raises the risk of osteoporosis and fractures, anemia, loss of muscle, low mood and, in women with early estrogen loss, heart disease. With hormone replacement most symptoms improve within weeks to months, and bone density improves over a year or two. Secondary causes such as obesity, opioids or prolactinomas can sometimes be fully reversed.

Frequently asked questions

What is the difference between primary and secondary hypogonadism?

In primary hypogonadism, the testes or ovaries themselves are damaged, so LH and FSH from the pituitary are high. In secondary hypogonadism, the pituitary or hypothalamus fails to send signals, so LH and FSH are low or normal. The type guides further tests and fertility options.

Is hypogonadism the same as low testosterone?

In men, low testosterone is the main feature of hypogonadism, so the terms overlap. Hypogonadism is broader: it also includes low sperm production and applies to women, where it means low estrogen and ovarian function. See our page on low testosterone for male-specific detail.

Can hypogonadism be cured?

Some forms can. Secondary hypogonadism caused by obesity, opioids, anabolic steroids, high prolactin or a treatable pituitary tumor may reverse when the cause is treated. Genetic or primary causes are usually permanent and managed with lifelong hormone replacement.

Can you have children with hypogonadism?

Often, yes. People with secondary hypogonadism can usually be treated with hormone injections to produce sperm or ovulate. In primary hypogonadism, options include sperm retrieval and IVF in men, and donor eggs in women.

What are the symptoms of hypogonadism in women?

The main symptoms are irregular or absent periods, hot flashes, night sweats, vaginal dryness, low sex drive and difficulty getting pregnant. In girls it causes absent breast development and periods. Low estrogen also causes bone loss over time.