Luteinizing Hormone Deficiency

Introduction:

Luteinizing hormone is important for inducing puberty and regulating sexual functioning. The luteinizing hormone plays a crucial role in each menstrual cycle phase. The hypothalamic-pituitary-gonadal axis regulates the release of luteinizing hormone. Both male and female infertility can be caused by luteinizing hormone deficiency. Luteinizing hormone deficiency is associated with Kallmann syndrome in men. In women, luteinizing hormone deficiency prevents ovulation and may result in irregular menstrual cycles.

What Is Luteinizing Hormone?

Luteinizing hormone (LH), also called lutropin or lutrophin, is a hormone responsible for regulating reproductive functioning. Luteinizing hormone is produced and secreted by the anterior pituitary gland. The pituitary gland is an endocrine gland that is small and responsible for several bodily functions. It is also responsible for regulating the functioning of the various endocrine glands. However, the hypothalamus also plays a vital role in producing the luteinizing hormone. The hypothalamus produces and secretes the gonadotropin-releasing hormone, which regulates the secretion of luteinizing hormone from the anterior pituitary gland. The primary function of the luteinizing hormone is the regulation of the functioning of ovaries and testes in women and men, respectively.

What Is the Function of the Luteinizing Hormone?

Luteinizing hormone is responsible for carrying out the following functions:

• In Men: The testosterone production by Leydig cells in the testes is stimulated by the luteinizing hormone. Testosterone is an androgen (male sex hormone) responsible for sperm production. Testosterone is also responsible for developing secondary sexual characteristics like facial and body hair growth, increased muscle mass, deepening of the voice, etc.

• In Women: Luteinizing hormone plays different roles during the menstrual cycle. During the first and the second week of the menstrual cycle, the luteinizing hormone is necessary to stimulate the ovarian follicles to produce estradiol (female sex hormones). The luteinizing hormone surges and increases in level to cause ovulation around day 14 of the cycle. Ovulation is the process of releasing a mature egg from the ovaries. Moreover, at around weeks three and four, the luteinizing hormone is responsible for the production of progesterone (progestogen sex hormone) which is a hormone that helps in supporting the initial stages of pregnancy.

How Is Luteinizing Hormone Regulated?

• The hypothalamic-pituitary-gonadal axis is a system that controls luteinizing hormone release from the anterior pituitary gland. This system involves the hypothalamus, the pituitary gland, and the gonads (testes or ovaries).

• The hypothalamus releases the gonadotrophin-releasing hormone, which then binds to target receptors in the anterior pituitary gland, thus stimulating the production and secretion of luteinizing hormone.

• The bloodstream carries the released luteinizing hormone, which attaches to the target receptors in the testes or ovaries to regulate the synthesis of sperm or eggs.

• A negative feedback loop regulates the level of luteinizing hormone. The secretion of hormones from the testes or ovaries (gonads) can reduce the secretion of gonadotrophin-releasing hormone (GnRH) and luteinizing hormone. Moreover, the gonadotropin-releasing hormone and luteinizing hormone levels rise when the hormones secreted from the gonads drop.

What Is Luteinizing Hormone Deficiency?

Luteinizing hormone levels in the body drop below the average biological range, known as luteinizing hormone deficiency. Luteinizing hormone deficiency is a type of hypogonadism (decreased or absent hormone secretion or other gonadal function). Luteinizing hormone and follicle-stimulating hormone deficiencies always coexist because of the same origin of secretion. Isolated luteinizing hormone deficiency is rare but can occur in certain conditions. Luteinizing hormone deficiency can be congenital (present at birth) or acquired. Due to the necessity of luteinizing hormone for supporting proper testicular and ovarian function, luteinizing hormone deficiency can cause infertility in both men and women. Luteinizing hormone deficiency can also lead to delayed puberty, reproductive abnormalities, dysfunction of the gonads, irregular menstrual cycles, etc.

What Causes Luteinizing Hormone Deficiency?

The causes of luteinizing hormone deficiency can be classified into hypothalamic and pituitary causes-

Hypothalamic Causes of Luteinizing Hormone Deficiency Are:

• Kallmann Syndrome: Kallmann syndrome is a congenital (condition present at birth) cause of luteinizing hormone deficiency. It occurs as a result of genetic variations that occur due to the failure of differentiation or migration of gonadotropin-releasing hormone neurons.

• Luteinizing Hormone Beta-Subunit Mutations: In this case, the level of luteinizing hormone is high, but the beta sub-unit mutated hormone has reduced functional capabilities.

• Stress-Related: Due to prolonged vigorous activity, significant weight loss, and hypothalamic suppression, stress-related luteinizing hormone deficiency can occur.

Pituitary Causes of Luteinizing Hormone Deficiency Are:

• Sheehan Syndrome: Sheehan syndrome affects the pituitary gland and is caused by severe bleeding during childbirth. As a result, all pituitary gland hormones become absent or produced in low amounts.

• Hyperprolactinemia: Typically, a prolactin-secreting pituitary tumor causes hyperprolactinemia. High prolactin levels block the anterior pituitary's ability to secrete luteinizing hormone.

Is Luteinizing Hormone Deficiency a Common Condition?

• Luteinizing hormone deficiency is a rare condition, and it is reported in 1 in 10,000 to 1 in 86,000 individuals.

• Kallmann syndrome is linked to over 66 % of cases of luteinizing hormone deficiency. In addition, men tend to be more prone to Kallmann syndrome.

• Stress-related luteinizing hormone deficiency accounts for 30 % of all cases.

What Are the Symptoms of Luteinizing Hormone Deficiency?

Symptoms of luteinizing hormone deficiency are:

• Anosmia (inability to sleep) or hyposmia (reduced sense of smell) is associated with Kallmann syndrome.

• Delayed puberty.

• Lack of secondary sexual character; reduced facial and body hair; lack of deep voice: absence of pubic hair, etc.

• Small penis in men and underdeveloped breasts in women.

• Irregular menstrual cycles (primary amenorrhea) in women.

• Gynecomastia (development of breasts) in men.

• Loss of appetite, stress, and unusual weight loss in women of reproductive age.

• Reduced sex-drive.

• Erectile dysfunction.

• Visual problems and persistent headaches occur in the case of pituitary tumors.

• Infertility.

• Galactorrhea in men (abnormal milky discharge from nipples).

How Is Luteinizing Hormone Deficiency Diagnosed?

Luteinizing hormone deficiency is diagnosed in the following ways:

• The patient's detailed clinical and medical history can help diagnose luteinizing hormone deficiency.

• Serum level of thyroid-stimulating hormone (TSH) should be done to rule out the chances of hypothyroidism (underactive thyroid gland).

• Blood examinations are done to check the levels of luteinizing hormone, prolactin (the hormone responsible for milk production), follicle-stimulating hormone, and estradiol (female sex hormones). The presence of low estradiol levels, along with low or normal luteinizing hormone and follicle-stimulating hormone levels, indicate a hypothalamic issue. In addition, elevated levels of prolactin suggest pituitary problems.

• Magnetic resonance imaging (MRI) of the head should be done to examine abnormalities in the pituitary and hypothalamus, particularly pituitary gland tumors.

How Is Luteinizing Hormone Deficiency Treated?

The underlying cause of the condition, age of the patient, gender of the patient, and desire for fertility affect how luteinizing hormone deficiency is treated. Therefore, luteinizing hormone deficiency is treated in the following ways:

• Estrogen therapy is used to induce the development of secondary sexual characteristics in females who have delayed puberty. When adult women with luteinizing hormone deficiency want to conceive, they will be given injectable gonadotropins (hormones secreted by the pituitary to stimulate gonads) to induce ovulation.

• Testosterone is administered to males with delayed puberty due to hypogonadism associated with luteinizing hormone deficiency. Moreover, in men who do not desire fertility, testosterone therapy is used to increase sex drive and secondary sexual characteristics.

• Treatment for pituitary disorders depends on the underlying cause and hormonal imbalance.

• Dopamine agonists are used for treating hyperprolactinemia (increased levels of prolactin) caused by pituitary gland tumors. However, prolactinomas that are persistent need surgery and constant follow-ups.

Conclusion:

Luteinizing hormone deficiency associated with Kallmann syndrome requires life-long hormone replacement therapy to maintain normal sexual functioning and fertility. Stress-related luteinizing hormone deficiency usually subsides after alleviating stress, and the condition usually has a good prognosis. Pituitary gland tumors usually either resolve spontaneously or go away after surgical treatment. Luteinizing hormone deficiency that is left untreated can cause infertility, and if the deficiency occurs before puberty, the individual will not attain puberty and fail to develop secondary sexual characteristics. However, the condition can be managed after treatment, and treatment generally has a good prognosis.