What is Luteinizing Hormone Deficiency?
Luteinizing hormone (LH) is a type of protein-based hormone produced in the pituitary gland. It’s released in response to signals from the hypothalamus – another part of the brain – that releases gonadotropin-releasing hormone (GnRH). Various conditions can result in a decrease in LH as a way to keep the body’s internal balance or in response to a system that controls brain and sex glands. However, it’s rare to have a deficiency of LH by itself. This usually happens when someone takes external testosterone, which can decrease or stop LH production due to its countering effect.
Most of the time, when there is a deficiency of LH, there is also a deficiency of another hormone called follicle-stimulating hormone (FSH). This is because both these hormones are produced by the same cells in the pituitary gland. LH plays a crucial role in preparing the reproductive cells in both males and females for reproduction. In men, it signals the testes to produce testosterone, while in women, it prompts the ovaries to make certain hormones and plays a vital role in releasing an egg for potential fertilization.
LH and FSH are key hormones in the control system involving the hypothalamus, pituitary gland, and the sex organs. If they are lacking, it can result in delayed puberty, reproductive abnormalities, and a medical condition known as hypogonadism which involves lower than normal levels of sex hormones. The symptoms vary depending on whether the deficiency starts before or after puberty.
What Causes Luteinizing Hormone Deficiency?
A deficiency of LH, or Luteinizing Hormone, can either be something you’re born with (congenital) or something you develop later (acquired). Depending on how our reproductive axis — a system involving the hypothalamus in the brain, the pituitary gland, and the gonads — functions, LH deficiency can be divided into two categories: causes related to the hypothalamus and causes related to the pituitary gland.
Let’s talk about the hypothalamus-related causes first.
1. Kallmann Syndrome: This is a congenital, or in-born, cause of LH deficiency, often associated with decreased to no sense of smell. This happens due to certain genetic mutations which interfere with the development or movement of a specific group of neurons that produce a hormone called GnRH (gonadotropin-releasing hormone). Some studies show that mutations in a gene known as KISS1 might cause this. The KISS1 gene is responsible for kisspeptin hormone, an important player in the reproductive system. A decrease in GnRH hormone results in a lowered production of sex hormones, which may appear as a lack of puberty and sexual development.
2. LH beta-subunit mutations: Such mutations are defects in the beta subunit of LH or the LH receptor, leading to fertility issues and the absence of menstruation because of the decrease in LH levels needed for ovulation. In this situation, the LH hormone levels may seem high compared to normal, but the mutated hormone is not functional.
3. Idiopathic hypogonadotropic hypogonadism (IHH): This condition results from the complete or partial lack of GnRH-induced release of hormones called LH and FSH. This means that there’s not enough activation to release LH and FSH. IHH is quite rare and can occur in both men and women.
4. Stress-related hypogonadotropic hypogonadism: This is brought about by suppressing the hypothalamus because of prolonged intense physical exercise and extreme weight loss. Both these conditions result in an increase of a hormone known as corticotropin-releasing hormone (CRH), which prevents the regular release of GnRH from the hypothalamus. This results in low FSH and LH levels, which may appear as the absence of menstruation.
Now, let’s discuss pituitary-related causes.
1. Hyperprolactinemia: This condition most commonly happens due to a pituitary tumor that secretes prolactin. High prolactin levels prevent the secretion of FSH and LH from the anterior pituitary and can result in hypogonadism, fertility issues, and galactorrhea (a condition where a woman’s breasts leak milk even when she is not pregnant or breastfeeding).
2. Sheehan Syndrome: This happens because of heavy bleeding during childbirth, which causes damage to the pituitary gland due to lack of blood supply. It results in the reduction or loss of all hormones produced by the pituitary gland, including the reproductive hormones FSH and LH.
Apart from these, other causes from the pituitary side include pituitary tumors, infections, inflammation, strokes, and trauma.
Risk Factors and Frequency for Luteinizing Hormone Deficiency
Hypogonadotropic hypogonadism (HH), a condition prevalent in both men and women, ranges in occurrence from 1 in 10,000 to 1 in 86,000. Kallmann Syndrome, more common in men, is implicated in about 66% of the cases. This syndrome is often discovered in children who have delayed puberty.
A variant of the condition, stress-related hypogonadotropic hypogonadism, is frequently seen in young women, and is responsible for about 30% of cases of secondary amenorrhea, a term for missed periods.
While pituitary tumors are rare and can occur at any age, they are commonly diagnosed in late adulthood. In addition, there’s a form of the disorder termed ‘idiopathic’ because its cause is unknown, and can also transpire at any age.
Signs and Symptoms of Luteinizing Hormone Deficiency
Kallmann syndrome is a condition that results in a lack of a sense of smell (anosmia) or a weak sense of smell (hyposmia) along with delayed puberty. People with this condition may lack secondary sexual characteristics such as reduced body and facial hair, a deep voice, and pubic hair. This often results in a body shape characterized by long limbs compared to the torso, poor muscle development, small testicles, and a small penis in men. In women, it could lead to a lack of breast development and an absence of menstruation. Some men with Kallmann syndrome may also have gynecomastia, a condition characterized by enlarged breast tissue.
Stress-related hypogonadotropic hypogonadism is commonly seen in women in their reproductive years who have recently experienced significant stress or excessive weight loss, such as that caused by anorexia nervosa. Factors contributing to the weight loss and subsequent hypogonadism can include excessive physical activity, mental health conditions like anorexia nervosa, and malnutrition.
Idiopathic hypogonadotropic hypogonadism (IHH) presents similarly in children to Kallmann syndrome, with the exception of the lack of smell. In adults, IHH can cause sexual problems such as loss of sex drive and erectile dysfunction in men, and absence of periods in women.
Individuals with pituitary tumors may experience different symptoms, but common ones include visual problems and headaches. Hyperprolactinemia, a condition characterized by excessive amounts of the hormone prolactin in the blood, can cause a lack of menstruation and abnormal milk production in women, and impotence, infertility, and hypogonadism in men. Although less common, men with this condition may also experience abnormal milk production.
Testing for Luteinizing Hormone Deficiency
When it comes to suspected issues with the thyroid or hormonal imbalance, laboratory tests are often the first step. Your doctor may test the level of thyroid-stimulating hormone (TSH) in your blood to check if you have hypothyroidism, a condition where the thyroid gland doesn’t produce enough hormones. For women, a pregnancy test might also be run.
The doctors will also check the levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), and prolactin (PRL) in your blood. These are hormones that play a major role in sexual development and fertility. Sometimes, tumors in the pituitary gland at the base of the brain can grow upwards and interrupt the delivery of dopamine to the pituitary stalk. Dopamine helps to control the levels of prolactin, and when it’s stopped, this can lead to high prolactin levels, a condition known as hyperprolactinemia.
If you have a condition known as Kallmann syndrome, the doctors may also carry out an olfactory test. Kallmann syndrome is a genetic disorder that affects your sense of smell and your body’s sexual development. People with this syndrome are often unable to smell (anosmia), and this test can help confirm the diagnosis.
In addition to lab tests, you may also need to have a magnetic resonance imaging (MRI) scan of your head. An MRI scan uses strong magnetic fields and radio waves to produce detailed images of the inside of your body. This test can help your doctor check for any structural abnormalities in the hypothalamus (a part of your brain that has important functions including the release of hormones) and the pituitary gland, especially for any tumors known as pituitary adenomas.
Treatment Options for Luteinizing Hormone Deficiency
In cases of LH deficiency, the treatment depends on the cause, age, gender of the patient, and whether the patient wants to have children in the future or not.
For young boys who haven’t hit puberty yet, a type of medicine called androgen, specifically testosterone, can help start puberty and the development of adult male characteristics. These medicines come in different forms such as skin patches, gels, injections, and pills. Generally, starting testosterone treatment around the age of 12 to 14 is advised to help induce puberty.
If a man who has already reached puberty has LH deficiency, he might also be given testosterone replacement therapy. This treatment can reverse the signs and symptoms of a condition called hypogonadism, affecting the body’s ability to produce testosterone. This treatment can also help with other conditions related to low testosterone levels such as low red blood cell count (anemia), decreased bone density, muscle wasting, and changes in mood or mental abilities. If a man wishes to father children, there are treatments available that can help increase fertility. It’s important to note that these treatments can take up to two years to work before sperm production starts.
In girls who haven’t reached puberty yet, estrogen therapy is used to start puberty and cause breast development. Estrogen can be given as a pill, a gel to be applied on the skin, or a patch. The decision of when to start estrogen treatment is tailored to each individual and depends on factors such as the girl’s age, bone age, height, and emotional and social considerations.
In women who wish to have children, there are treatments available to stimulate ovulation, the process where the ovary releases an egg ready for fertilization. This can be done using a combination of estrogen therapy and hormones called gonadotropins. It’s crucial to understand that regular estrogen treatment by itself does not induce ovulation. Removing stress or gaining weight could also help restore normal hormone levels in women whose LH deficiency is linked to these factors.
If the LH deficiency is due to a pituitary disorder, the treatment will depend on the specific cause and the hormonal imbalance involved. One such condition is hyperprolactinemia, where the pituitary gland in the brain produces too much of a hormone called prolactin. This can be managed effectively with certain types of medication. In cases that do not respond to medication, surgery may be necessary followed by regular check-ups.
What else can Luteinizing Hormone Deficiency be?
Luteinizing hormone deficiency is a type of condition that results in below normal production of sex hormones. It is important to distinguish this from other conditions that result in similar symptoms – these can include conditions that affect the sex organs directly, or other disorders that influence the production of hormones in the brain. Once this type of hormone deficiency is diagnosed, the next step is to determine the cause.
When diagnosing luteinizing hormone deficiency, doctors try to rule out the following conditions:
- Primary hypogonadism
- Primary amenorrhea (the absence of menstrual periods in a woman of reproductive age)
- Hypogonadism due to thyroid problems
- Luteal phase dysfunction (a condition affecting the latter part of the menstrual cycle)
- Prolactinoma (a benign tumor of the pituitary gland that produces a hormone called prolactin)
- Ovarian insufficiency (a failure of the ovaries to function normally)
- Decreased sperm production
- Polycystic ovarian syndrome (a hormonal disorder common among women of reproductive age)
The aim for the doctor is to consider all these conditions carefully, and to perform necessary tests to accurately diagnose the underlying cause.
What to expect with Luteinizing Hormone Deficiency
People with Kallmann syndrome or unexplained low sex hormones (known as genetic idiopathic hypogonadotropic hypogonadism) need continuous hormone replacement therapy. This is essential for normal sexual function and fertility. In some cases, however, fertility may not return as everyone responds differently to this hormone therapy.
Pituitary adenomas, which are small, noncancerous tumors in the pituitary gland, may shrink on their own if they are tiny (a condition referred to as microadenomas). However, these microadenomas need to be checked regularly. Larger pituitary tumors, or macroadenomas, need to be watched through regular imaging tests at least once a year. These larger tumors might need to be surgically removed if they continue growing.
Low sex hormone levels caused by stress usually get better once the stress is managed, and it generally has a good outlook. Weight-loss related low sex hormone levels, like in the eating disorder anorexia nervosa, often get better once a healthy weight is achieved.
Possible Complications When Diagnosed with Luteinizing Hormone Deficiency
If LH deficiency isn’t treated, it can cause infertility. In cases where it happens before puberty, the person won’t go through puberty and won’t develop secondary sexual characteristics. Additionally, a lack of testosterone can lead to loss of muscle mass, weakened bones, and a decrease in sex drive in men.
Side Effects of Untreated LH Deficiency:
- Infertility
- Failure to go through puberty
- Lack of secondary sexual characteristics
- Loss of muscle mass
- Weakened bones
- Decreased sex drive in men
Preventing Luteinizing Hormone Deficiency
Having low levels of a hormone called LH can cause problems such as infertility or not going through puberty. It’s crucial for patients and their families to understand how this works. For these issues, hormone replacement therapy can be an effective solution and it is important to start the treatment as soon as the delay in hitting puberty or the cause behind it is identified. For older men, a type of therapy known as gonadotropin therapy can help with fertility issues. However, the effectiveness of the therapy varies from person to person. Therefore, it’s not guaranteed that fertility will be achieved, and much depends on how the body responds and if the treatment plan is followed religiously.
Women with low LH levels should consider estrogen replacement therapy. If they wish to become pregnant, it is often advised to contact a reproductive endocrinology specialist. This specialist focuses on the function of the reproductive system and can provide expert advice on these issues.
Last but not least, it’s important for patients to know about the possible side effects of hormone therapy. Understanding these possible effects can help patients make informed decisions about their treatment plan, and help them to feel more in control of their health and well-being.
