Hypogonadotropic Hypogonadism: The Complete Guide

Take-home points‍

• Hypogonadotropic hypogonadism is when a man has low testosterone levels, but an issue outside the testicles is responsible.
• Low sex drive, erectile dysfunction, thinning hair, and infertility are some of the most common symptoms.
• Treatment depends on where the issue is and a man’s fertility goals. Testosterone is the most common treatment.
• With treatment, symptoms usually improve, and men can go on to have children.
  

What is hypogonadotropic hypogonadism (HH)?

Hypogonadotropic hypogonadism (also known as secondary hypogonadism) is when the sex organs (the testicles or ovaries) aren’t producing enough sex hormones. For men, this means the testicles aren’t producing enough testosterone.

With primary hypogonadism, the issue is with the testicles themselves. But with secondary hypogonadism (HH), the issue is to do with the hormonal signals the testicles are receiving. To produce testosterone, the testicles need stimulation from two main hormones: luteinizing hormones (LH) and follicle stimulating hormone (FSH). These hormones are produced from the pituitary gland at the bottom of you brain and released into the blood.¹

However, for the pituitary gland to produce LH and FSH, it also needs to be stimulated by gonadotropin releasing hormone (GnRH). GnRH itself is released from a part of the brain called the hypothalamus. When a problem with either the pituitary gland or the hypothalamus disrupts the production of these hormones, this leads to hypogonadotropic hypogonadism.¹

Learn more about hypogonadism causes, diagnosis, and treatment

What causes hypogonadotropic hypogonadism?

We’ve already discussed that problems in the hypothalamus (a part of the brain) or the pituitary gland (hormone-producing gland at the bottom of the brain) cause hypogonadotropic hypogonadism. But what could these problems be? Broadly speaking, the causes of hypogonadotropic hypogonadism can be inherited or non-inherited.

Inherited causes of hypogonadotropic hypogonadism

Inherited causes are passed on in your genes and tend to run in families. One example includes Kallmann syndrome. With this condition, a gene mutation causes the cells in the hypothalamus that produce GnRH to not develop correctly.² This means GnRH is not secreted properly, which has a knock-on effect on FSH and LH (which stimulate the testicles to produce testosterone), and testosterone production.

Non-inherited causes of hypogonadotropic hypogonadism

Non-inherited causes of hypogonadotropic hypogonadism include infection, drugs, tumours, trauma, severe or chronic illnesses, iron overload (due to a medical condition), and hyperprolactinaemia (high levels of a hormone called prolactin).³

Another cause that’s receiving more attention recently is functional hypogonadotropic hypogonadism. This type of hypogonadotropic hypogonadism is diagnosed once other obvious causes have been ruled out. The hypothalamus and/or the pituitary are affected, but the reason why is unclear. Originally, it was though that this type of hypogonadotropic hypogonadism was due to ageing. However, more recent evidence suggests that type 2 diabetes and obesity are involved. Infections like HIV, low energy availability, and different drugs may also have an impact.⁴

How common is hypogonadotropic hypogonadism?

Primary hypogonadism, also known as hypergonadotropic hypogonadism, is much more common than hypogonadotropic hypogonadism in adult men.¹ Hypogonadotropic hypogonadism is less common, affecting between 1 in 10,000 and 1 in 86,000 men.⁵

Hypogonadotropic hypogonadism symptoms

As the causes of hypogonadotropic hypogonadism are different, the symptoms can appear at different stages of life. If the cause is present from before puberty, the development of a boy’s penis and testicles will be affected. Boys may also have:¹

• Thin bones.
• Poor muscle mass.
• Fat around their abdomen.
• Anaemia (low oxygen levels in their red blood cells).
  

If hypogonadotropic hypogonadism happens after puberty, a man’s sexual development shouldn’t be affected. But they may experience low sex drive, hair thinning, growth of breasts, anaemia, and loss of bone and muscle mass. These symptoms are all due to the lack of testosterone. A man’s fertility can be lower than normal as sperm may not be produced effectively.

Hypogonadotropic hypogonadism diagnosis

Hypogonadotropic hypogonadism is usually suspected when the symptoms we’ve discussed are present. If a boy is late to go through puberty, and isn’t showing any signs like hair growth or sexual development, HH may be suspected. In these cases, a blood test to check hormone levels is needed. Even if hormone levels suggest hypogonadotropic hypogonadism, the condition isn’t officially diagnosed until the boy is 18, as it may be delayed puberty.

In adult men, hypogonadotropic hypogonadism may be considered if they’re experiencing a reduced sex drive, erectile dysfunction, or weight gain. But for many men, they don’t realise anything is wrong until they start trying for a baby. Infertility testing may highlight that a man has HH, even if he’s not experiencing other symptoms. Luckily, there are some treatments to help with fertility (more on this in the next section).

For an official diagnosis, blood testosterone levels (taken in the morning) must be low, alongside low levels of FSH, LH, or both.¹ If LH and FSH are both normal or high, it’s likely to be primary (or hypergonadotropic) hypogonadism rather than hypogonadotropic hypogonadism. Extra blood tests or scans may also be done to work out the cause of hypogonadotropic hypogonadism.

Hypogonadotropic hypogonadism treatment

The type of treatment depends on the cause, how much the symptoms impact a man’s life, and his fertility goals. Testosterone replacement therapy is the most common treatment, and can be effective at improving sex drive, hair loss, muscle, and bone mass. Usually, the aim is to use artificial testosterone to get blood testosterone levels into a normal range. However, testosterone supplements don’t usually help with fertility.

For men who are hoping to have children, other treatment options may be more helpful. In hypogonadotropic hypogonadism, the problem isn’t with the testicles, but with the hormones that stimulate them to work. So artificial hormones can be used to replace them.

The type of replacement hormone depends on where the issue is. If the problem is with the hypothalamus, replacement GnRH is used. If it’s with the pituitary gland, replacement FSH and/or LH is used. This can help stimulate the testicles to produce testosterone and sperm, although levels may still be below normal. Often, the amount of sperm is still enough to achieve pregnancy. In cases where a man is still struggling, there are other fertility treatments that can help.^1,3

Alongside any hormones, the cause of hypogonadotropic hypogonadism will also be treated if it’s reversible. This could be an infection that needs antibiotics, surgery to remove a tumour, or lifestyle changes to improve the causes of functional hypogonadotropic hypogonadism.

Learn more about treatment options for hypogonadism

If you’re experiencing any of the symptoms discussed on this page, or you’re worried about your fertility, book an appointment with a healthcare professional. Find more information about hypogonadism on the NHS website.

References

1. Fraietta R, et al. Clinics (Sao Paulo). 2013;68 Suppl 1(Suppl 1):81-8.
2. Sonne J, Lopez-Ojeda W. Kallmann Syndrome. In: StatPearls 2023.
3. Darby E, Anawalt BD. Treat Endocrinol 2005;4(5):293–309.
4. Spaziani M, et al. Front Endocrinol (Lausanne) 2023 Jun 29;14:1184530.
5. Hayes FJ, et al. Endocrinol Metab Clin North Am 1998;27(4):739–63.