The menopausal period is characterized by the absence of menses for at least 12 consecutive months , by changes in hormonal secretions and other physiological changes.
The cyclical cessation of ovarian activity and the fertile season normally occurs around the average age of 50 years (+ or – 5 years). However, due to ovarian dysfunction, certain diseases, genetics or particular medical procedures, some women enter menopause early, under the age of 40. This natural or induced condition is known as early (or premature) menopause .
In addition to dealing with hot flashes , mood swings and other typical symptoms that accompany climacteric , many women in early menopause have to cope with additional emotional and physical problems (infertility, reduction of bone density , metabolic effects that can compromise numerous organs etc.).
What Is Early Menopause?
Early menopause coincides with the loss of ovarian activity (and the consequent disappearance of menstrual cycles) before the age of 40 . This condition can occur spontaneously or induced , due to bilateral ovariectomy surgery or pharmacological or radiotherapy ovarian suppression . The phenomenon affects approximately 1-3% of Italian women of reproductive age.
Premature Ovarian Failure (Pof)
Premature Ovarian Failure (Pof): What It Means And What Causes It
Premature menopause is also indicated with the term POF ( Premature Ovarian Failure ); this term refers to premature ovarian failure with amenorrhea , elevated serum gonadotropins ( FSH and LH ), and hypoestrogenism ( decreased plasma estradiol ).
In reality, the two conditions are not exactly equivalent:
- Premature ovarian failure can be considered a transitory phenomenon , since in many cases intermittent spontaneous ovarian activity can occur for years, characterized by occasional menstrual periods alternating with others of amenorrhea (absence of menstruation for at least three months). Women with premature ovarian failure are still able to produce estradiol (so ovulation can occur ) and can sometimes be able to become pregnant .
- The patient with early menopause stops menstruating completely (and permanently) and is therefore unable to get pregnant.
In women with premature ovarian failure:
- There are dysfunctional primordial follicles, which are physiologically unpredictable and absolutely irregular;
- Ovulation can occur in 5-10% of cases.
When POF becomes a permanent condition , it equates to early menopause.
What Are The Causes Of Premature Menopause?
At the basis of the onset of early menopause there is a follicular atresia (arrest of the development of the follicle ), generated by multiple causes, some complex and others of a primitive nature.
In two thirds of cases, early menopause is considered idiopathic : the specific cause at the origin of the condition cannot be identified and the karyotype does not show any alterations (ie there are no specific genetic abnormalities that predispose to early menopause).
The possible causes that promote early menopause are:
Genetic (Hereditary) Abnormalities
Some genetic syndromes and chromosomal alterations , evident on karyotype analysis , are associated with premature menopause.
Some examples involve mutations on the X chromosome and include:
- Fragile X chromosome syndrome , caused by a particular mutation of the FMR1 gene, located on the X chromosome;
- Turner syndrome (45,X) , in which menopause precedes menarche and ovarian function is absent;
- Swyer syndrome (pure gonadal dysgenesis): involvesunderformed and non- functional gonads .
Inherited enzyme/metabolic defects may also promote early menopause:
- Galactosemia : systemic pathology caused by the malfunctioning of enzymes that perform the function of metabolizing galactose ; as a result, the body is unable to convert it into glucose . Unconverted galactose is thought to produce an ovarian toxic effect ;
- Congenital adrenal hyperplasia : autosomal recessive disease affecting the adrenal glands and characterized by disorders in the biosynthesis of steroid hormones ;
- Mucopolysaccharidosis : systemic metabolic diseases, caused by specific enzyme deficiencies. These diseases are classified among the heterogeneous group of lysosomal storage diseases.
The autoimmune diseases that coexist with early menopause can be of two types:
- The immune system mistakenly produces anti-ovarian antibodies (antifollicle, anti- corpus luteum , anti- pituitary hormone receptors , etc.);
- Premature ovarian failure can be associated with other systemic autoimmune diseases, especially of the thyroid type ( hypothyroidism ) or affecting the adrenal gland , as in the case of Addison’s disease (it limits the production of hormones secreted by the adrenal glands). Other systemic autoimmune conditions to be considered in early menopause are Crohn’s disease , systemic lupus erythematosus , and rheumatoid arthritis .
The histological picture that characterizes patients with autoimmune premature ovarian failure is the presence of oophoritis (inflammation of the ovary).
Viral And Bacterial Infections
Certain viral infections , such as cytomegalovirus or mumps , or bacterial infections ( tuberculosis ) are thought to contribute to early menopause in some patients. Mumps , in fact, has among its complications the inflammation of the ovary (oophoritis), which, if it becomes chronic , is able to compromise the functionality of the organ. The same process is triggered by Koch’s bacillus , which in addition to affecting the lungs , can trigger genital tuberculosis and consequently oophoritis.
Iatrogenic Causes: Induced Premature Menopause
In these cases the menopause is premature due to a therapeutic procedure which can be pharmacological (chemotherapy), radiation or surgery. These treatments produce different consequences on fertility, associated symptoms, etc.
- Pharmacological therapies : early menopause is a condition that can be promoted by chemotherapy . Obviously, this effect depends on many factors, including the age of the woman, the types of drugs used and the dosage. Some of the chemotherapy drugs that can promote the condition are: alkylating agents , cyclophosphamide and busulfan ; with minor ovarian toxic effects: methotrexate and fluorouracil . The damage promoted by chemotherapy is gradual and, once the cure is finished, there can be a complete reactivation of ovarian activity.
- Radiotherapy : the damages induced by radiotherapy are irreversible only if the irradiation is carried out at the pelvic level and with a particularly high dosage. Ovarian recovery is, therefore, possible.
- Surgical menopause : bilateral ovariectomy (removal of both ovaries) and hysterectomy ( removal of the uterus ) are surgical interventions that favor the precocity of menopause. These interventions may be necessary for the presence of a tumor, ovarian cysts , severe endometriosis or other pathological conditions. Bilateral oophorectomy produces a rapid decrease in circulating levels of ovarian hormones and induces infertility permanently and immediately.
Even a wrong lifestyle , especially smoking and alcohol abuse , seems to bring forward the age of menopause. Furthermore, the existence of a family predisposition must be considered , for which the age at which the mother, grandmother or an older sister entered menopause should always be taken into consideration.
|Causes of premature menopause|
|Genetic causes||Chromosomal abnormalities / genetic syndromes|
|Systemic causes||Galactosemia, mucopolysaccharidosis|
|Immune causes||Systemic or organ autoimmune diseases|
|Iatrogenic causes||Chemotherapy, radiotherapy, surgical therapy|
|infectious causes||Viral (mumps), bacterial (TB)|
|Surgical causes||Ovariectomy, hysterectomy|
|Other causes||Idiopathic causes, lifestyles (smoking, alcohol), family predisposition|
Early Menopause Symptoms
Early Symptoms Of Early Menopause: How Do You Recognize Them?
The symptoms are generally difficult to interpret and are often the same that accompany natural menopause.
The clinical picture of early menopause can include:
- Sudden cessation or irregular onset of menstrual flows, with evident changes in the menstrual cycle : oligomenorrhea (alteration of the rhythm of the menstrual cycle), polymenorrhea (abnormal increase in the frequency of the cycle) and menometrorrhagia ( hemorrhagic profuse blood loss which occurs in conjunction with menstruation and tends to prolong its duration). The evolution of these signs is amenorrhea, ie the absence of menstruation for at least three months and, subsequently, their definitive disappearance;
- Aggravation of premenstrual syndrome ;
- Hot flashes : a sudden feeling of heat, followed by intense sweating , spreads over the upper body until the face and neck are flushed
These symptoms are a sign that the ovaries are producing less estrogen .
Other symptoms associated with early menopause
Along with the symptoms listed above, some women may experience:
- Vaginal dryness and pain during sexual intercourse ;
- Bladder control issues , such as incontinence or increased frequency of urination ;
- Irritability, mood swings , mild depression and insomnia (associated with decreased estrogen levels);
- Transient tachycardias ;
- Hair loss , dry skin and weight changes (weight gain);
- Decreased sex drive.
Early menopause can be emotionally devastating. One of the most common problems a woman has to face is the prospect of not being able to have children: the most immediate consequence of early menopause is infertility , caused by the drastic reduction of follicles and their deterioration.