Generality
Hypogonadism is an abnormal condition, characterized by a more or less marked reduction in the functional activity of the gonads, which in the man are the testicles, while in the woman they are the ovaries.
The presence of hypogonadism may depend on a problem inherent in the gonads (primary hypogonadism) or a problem on the hypothalamic-pituitary axis that controls the activity of the gonads (secondary hypogonadism).
The symptoms of hypogonadism vary according to the sex of the patient.
The therapy is, as a rule, of the hormonal type: in the woman, it consists in the exogenous administration of estrogens; in humans, in the exogenous administration of testosterone.
Brief review of the hypothalamus axis - pituitary - gonads
In humans, the gonads - the reproductive organs responsible for the production of sex cells or gametes - are under the control of hypothalamus and pituitary glands .
Here's how:
- Gland of the central nervous system, the hypothalamus secretes hormones of a proteic nature, called RH hormones or release hormones (NB: RH stands for relasing hormones ).
RH hormones are four in all and act on the pituitary gland, causing the secretion of other hormones.
- The hypothalamic RH hormones are: GnRH, TRH, GHRH and CRH.
Of interest for this article, it is only GnRH, or relasing hormone for gonadotropins . The function of GnRH is to stimulate the pituitary gland to secrete gonadotropins ( FSH and LH ).
- In the framework that includes the hypothalamus, the pituitary gland and the gonads, the pituitary gonadotropins FSH and LH have the task of stimulating the gonads to secrete the sex hormones .
Male and female sex hormones derive from cholesterol; in humans, their main representative is testosterone, while in women, they are estrogens and progesterone (NB: in humans, there are small amounts of estrogen and progesterone; similarly, in women, there are small amounts of testosterone).
What is hypogonadism?
Hypogonadism is the medical term that indicates a more or less marked reduction in the functional activity of the gonads, which in the man are the testicles, while in the woman they are the ovaries .
A reduction in the functional activity of the gonads leads to a decrease in the secretion of sex hormones.
WHAT ROLE DO THE MALE AND FEMALE SEXUAL HORMONES HAVE?
In general, sex hormones control the development of secondary sexual characteristics and the genital apparatus as a whole.
Going into the details of man and woman, male sex hormones regulate the development of the testicles, penis, pubic hair and muscles; female sex hormones, on the other hand, govern the growth of breasts and pubic hair, enlargement of the pelvis and the onset of menstruation.
MALE HYPOGONADISM AND FEMININE HYPOGONADISM
If it concerns man, the condition of hypogonadism is more precisely called male hypogonadism ; similarly, if the woman is interested, it is more specifically called female hypogonadism .
Male hypogonadism is a condition characterized by reduced testicular function, on which a testosterone deficiency depends.
Female hypogonadism, on the other hand, is that condition characterized by a reduced functionality of the ovaries, followed by less or no production of estrogens, progesterone and derived hormones.
Types
Experts on genital diseases consider that it is possible to classify hypogonadism according to various criteria.
According to the most common criterion, there is primary hypogonadism and secondary hypogonadism :
- Hypogonadism is defined as primary when it results from a defect or problem at the level of the gonads.
This means that the signals coming from the hypothalamus and pituitary gland are correct; what does not work properly are the reproductive organs.
Possible conditions responsible for primary hypogonadism are: Klinefelter syndrome, Turner syndrome, cryptorchidism, Noonan syndrome, etc.
- Hypogonadism is called secondary (or central), when it is the result of defects in the hypothalamus or pituitary gland.
This means that the gonads are healthy and would function properly, if there were not a problem upstream, at the level of the hypothalamic gland and the pituitary gland.
Conditions that can cause secondary hypogonadism are: Kallmann's syndrome, pituitary diseases, malnutrition, brain tumors involving the hypothalamus, opiate abuse, etc.
OTHER CLASSIFICATION CRITERION
The second most widespread criterion of classification of hypogonadism distinguishes the latter in: congenital hypogonadism and acquired hypogonadism .
- Hypogonadism is called congenital, when it is present from birth.
Possible causes of congenital hypogonadism are the aforementioned Turner syndrome and Klinefelter syndrome.
- Hypogonadism is defined as acquired, when those affected by it develop in the course of life, following particular triggering events.
Potential causes of acquired hypogonadism are: the so-called opioid-induced androgen deficiency (typical of those who have long abused codeine, morphine, etc.), infantile mumps, brain traumas involving the hypothalamus or pituitary gland, etc.
Causes
The main causes of primary hypogonadism are:
- Some genetic diseases affecting sex chromosomes, such as Turner syndrome (in women) or Klinefelter syndrome (in men)
- Cryptorchidism, in humans. This condition can induce hypogonadism in the event of failure to treat during childhood.
- Some forms of post-mumps orchitis, in humans. Orchite is the medical term for an inflammatory state in the testicles.
- Surgical interventions, reserved for sexual organs. In such situations, hypogonadism represents a surgical complication.
- Chemotherapeutic or radiotherapeutic treatments . Generally, chemotherapy or radiotherapy hypogonadism is temporary. The gonads, in fact, resume their natural function some time after the conclusion of the aforementioned therapies.
It is rare that radiotherapy and chemotherapy cause permanent infertility.
The most important causes of secondary (or central) hypogonadism, however, are:
- Kallmann's syndrome . It is a genetic disease, characterized by dysfunction of the hypothalamus, which does not produce the right amounts of GnRH.
The lack of production of GnRH impairs the secretion of FSH and LH by the pituitary gland; without adequate amounts of FSH and LH, the gonads do not secrete sex hormones;
- Pituitary diseases . These diseases compromise the hormonal secretion activity of the pituitary gland itself and this affects the gonads.
Among pituitary diseases, pituitary tumors deserve particular mention;
- Some inflammatory diseases, such as sarcoidosis, tuberculosis or histiocytosis, which affect the hypothalamus or pituitary gland, altering its activity;
- Some infectious diseases, such as AIDS;
- Prolonged use of opiate pain medications . Among the medicines of an opiate nature capable of causing secondary hypogonadism, there are: codeine, morphine, oxycodone, methadone, fentanyl, hydromorphine and dihydrocodeine;
- Obesity ;
- Aging ;
- Hemochromatosis . It is a genetic disease, usually hereditary, characterized by the abnormal accumulation of iron in various organs (including glands) of the body. For the tissues and organs in which it accumulates, iron can be very harmful, to the point of causing irreparable damage;
- Nutritional deficiencies due to malnutrition ;
- Brain surgery, from which a more or less serious lesion of the hypothalamus arises;
- Brain tumors involving the hypothalamus;
- Head trauma that specifically affects the hypothalamus or pituitary gland;
Symptoms and Complications
The symptoms of hypogonadism in humans are different from the symptoms of hypogonadism in women.
In male subjects, hypogonadism is responsible for: poor muscle development, abnormal growth of the breast, erectile dysfunction, reduced penis and testicular development, infertility (due to poor or no sperm production), recurrent sense of fatigue, decrease or absence of libido, osteoporosis, hair loss, hot flushes and difficulty concentrating.
By shifting attention to the female sex, hypogonadism in women is due to: absence of menstruation, poor breast development, hot flushes, hair loss, loss of libido and loss of a milky liquid from the breast.
SECONDARY HYPOGONADISM: THE SYMPTOMATOLOGICAL FRAMEWORK IS EXTENDED
In addition to showing the aforementioned symptoms, those suffering from secondary hypogonadism also complain of a series of disorders related to the condition that gave rise to hypogonadism.
To understand what has been said, it is useful to report the following example: a brain tumor, involving the hypothalamus, also causes headaches, visual disturbances and various hormonal dysfunctions (NB: it will be remembered that the hypothalamus produces several hormones).
Diagnosis
For a correct diagnosis of hypogonadism, the following are essential: physical examination, medical history and hormone dosage tests on a blood sample.
Sometimes, doctors may also consider it necessary to use some diagnostic imaging tests, including ultrasound, CT or nuclear magnetic resonance (NMR).
EXAMINATION OBJECTIVE
The physical examination is the medical evaluation of the symptoms reported by the patient.
Since it also includes the search for the most characteristic signs of hypogonadism, it is very common for the doctor to examine the muscle mass, the scalp and the appearance of the genitals.
EXAMS OF HORMONAL DOSAGE
Normally, hormone dosing tests on a blood sample from the patient include:
- Measurement of FSH (or follicle-stimulating hormone) and LH (or luteinizing hormone) levels;
- Measurement of estrogen levels in women;
- Measurement of testosterone levels in men;
In some circumstances, the doctor may also evaluate blood levels of iron, prolactin (a hormone of interest to women, which regulates breast growth and milk production) and thyroid hormones.
IMAGE DIAGNOSTIC TEST
Diagnostic imaging tests are useful, because they allow the doctor to assess the health of the internal genital organs or search for possible tumors in the brain or at the pituitary level.
Their prescription depends on what emerged during the previous examinations.
Treatment
To learn more: Drugs for the treatment of hypogonadism
In general, the treatment of hypogonadism varies according to the sex of the patient.
Thus, female hypogonadism requires treatment other than male hypogonadism.
The treatment of hypogonadism can be the same for both men and women, when at its origin there is some specific disease of the hypothalamus or pituitary gland, such as a hypothalamic tumor or a pituitary tumor.
THERAPY OF FEMALE HIPOGONADISM
The first-line treatment of female hypogonadism consists of estrogen-based hormone replacement therapy, in other words, exogenously administering estrogen .
Estrogen-based hormone replacement therapy, also known as estrogen replacement therapy, has the potential to promote endometrial cancer risk among its possible adverse effects.
According to some scientific studies, this risk could be limited by the combination of exogenous estrogens with a certain dose of progesterone.
In the case of low libido, exogenous administration of small amounts of testosterone is a good solution.
In case of irregular menstrual cycle or difficulty in conception, doctors could prescribe choriogonadotropin alfa (by injection) or exogenous FSH (in pills) to the patients.
Estrogen replacement therapy: the methods of administration
The most common exogenous estrogen intake modalities are two: through the application of a patch on the skin (via transdermal) or through ingestible pills (orally).
THERAPY OF THE MALE HYPOGONADISM
The first-line treatment of male hypogonadism consists of so-called testosterone replacement therapy (TRT), ie the exogenous administration of testosterone .
Among the side effects of TRT, the increased risk of cardiovascular diseases, including heart attack, deserves special mention. In this regard, in 2015, the FDA, that is the US government agency for the regulation of food and pharmaceutical products, required pharmaceutical companies that trade in exogenous testosterone to report, in the illustrative leaflets (under the heading undesirable effects), the possible increase in the risk of cardiovascular disease events.
Sometimes, in addition to the TRT, doctors may also consider the requirement of exogenous GnRH to be necessary. GnRH is useful in case of prepubertal patients (to promote puberty) and in case of reduced sperm production.
Testosterone replacement therapy: methods of administration
The possible ways of taking exogenous testosterone are: using a plaster or gel that can be applied to the skin (via the transdermal route), by injection (via parenteral route) and by swallowing tablets (orally).
SECONDARY HYPOGONADISM DUE TO A HYPOTALAMIC TEST OR HYPOFISARY
When the cause of hypogonadism is a tumor of the hypothalamus or pituitary gland, the treatment envisaged may consist of: surgery to remove the tumor mass, radiotherapy and / or chemotherapy.
Prognosis
The Urology Care Foundation - an American Foundation specializing in the field of urology - states that hypogonadism is a mostly chronic condition that requires life-long treatment.
The cases of secondary hypogonadism, whose causes are sometimes treatable even with good results, represent exceptions to what has just been said.
