It is known that, in contemporary Western society, the practice of physical exercise can have a positive effect on weight and body composition, on well-being diseases, and therefore life expectancy,
on certain enteric problems (for example constipation), on joint discomfort, on mood and mental balance and even on the success of the pregnancy.
On the other hand, on the other hand, excessive motor physical activity seems closely related to far from negligible negative effects, with sometimes serious repercussions on the body. Perhaps due to a later alignment with the contemporary sporting habits of the general population, the female sex is today the focus of numerous studies that analyze the correlation between motor physical exercise and general health; in particular, the interest of the scientific community seems to focus on:
Impact on life expectancy
Role in Fertility
Importance in pregnancy
Properties useful for the symptoms of premenopause
Prevention of osteoporosis
Overweight and obesity are increasingly common in developed countries, with significant consequences on the health of the general population. The evaluation criterion is the body mass index ( BMI), which however should be perfected by also inserting the constitution and the morphological type, or a measurement of the muscular circumferences and of the subcutaneous fat folds (plicometry); alternatively bio- impedancemetry can be used.
In overweight sedentary patients, in outpatient settings, to define the extent of this excess and consider the distribution of body fat, it is common practice to evaluate the waist circumference (WC, waist circumference) or the waist to hip ratio (WHR).) – the latter less and less used. This is because android -type adipose distribution is more correlated with metabolic, vascular and therefore death or permanent disability risks; in women this occurs especially after menopause, when the levels of female sex hormones drop.
The undeniable adverse effects of obesity on health are expressed, in particular, with the increased risk of type 2 diabetes mellitus, hypertension and other metabolic pathologies, therefore atherosclerosis and thrombosis, consequently cardio -cerebro-vascular events, as well as harmful effects on the reproductive system. It has been well demonstrated that weight loss in women is associated with a reduction in the risk of these pathologies in obese patients.
In particular, a high prevalence of obesity has been noted in the infertile population, thus demonstrating how body weight plays a fundamental role in the modulation of development and reproductive function. This occurs because the excess of fat favors an increase in estrogen levels, following an increase in the peripheral conversion – in particular of the fat tissue – from androstenedione to estrone, thus favoring a condition of anovularity, just as occurs in the syndrome of polycystic ovarian disease (PCOS).
Physical exercise and increased fertility in the obese
It has recently been demonstrated that obese women subjected to physical exercise for 24 weeks show a reduction in all the parameters measuring obesity, and in particular in WC – the main indicator of insulin resistance – therefore an important reduction in visceral fat ; this is demonstrated by the fact that women with reduced WC resume ovulation. The modification of this parameter therefore improves not only insulin sensitivity, but also plays an important role on the muscle, the major glucose storage site. This effect occurs because physical exercise increases the expression and activity of proteinsinvolved in the translation of the signal triggered by insulin on skeletal muscle. Moderate physical exercise, through the aforementioned mechanisms, favors an improvement in the regularity of menstrual cycles, therefore, with the resumption of ovulation, an increase in spontaneous fertility and that obtained with treatment is observed.
The beneficial effect of physical activity is also manifested in an improvement in pregnancy outcomes. Indeed, it has been demonstrated that women who have achieved a reduction in body weight following changes in their lifestyle have a lower probability of developing complications related to pregnancy, such as gestational diabetes, preeclampsia, and fetal malformations. A reduction in the abortion rate was also noted in these women.
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The negative effects of physical exercise can be explained by inverse mechanisms which often get confused and overlap with each other. These mechanisms are represented by exercise – induced weight loss and /or by the metabolic stress that physical exercise itself induces.
Exercise and amenorrhea
These mechanisms present themselves clinically with the clinical picture of amenorrhea, ie with the absence of spontaneous menstruation for at least 3 months. When this occurs, it is classically referred to as “female amenorrhea”. Female athletes’ amenorrhea can be classified into”primitive”amenorrhea, i.e. when the woman does not have the onset of menarche ( first menstruation), and secondary, when menstruation disappears after a more or less long period of spontaneous menstrual flows.”Exercise Amenorrhea”, along withand from anorexia nervosa) is part of the functional hypothalamic amenorrheas. The latter must be differentiated from hypothalamic amenorrhea due to organic causes, which include those secondary to tumor, ischemic or inflammatory pathology.
Those particularly at risk for amenorrhea from excessive physical exercise are above all those who practice sports such as swimming, fitness, classical dance, marathon (…). In these women, amenorrhea is primarily due to a reduction in body weight and a lack of fat mass ; these conditions are also aggravated by the reduction of caloric income by the subjects themselves.
Neuro-endocrine causes of amenorrhea in female athletes
Another important mechanism responsible for amenorrhea in athletes is that of neuro – endocrine stress, with a consequent increase in the inhibitory tone on the hypothalamus by oxytocin, serotonin and melatonin, therefore with reduced secretion of GnRH.
The hormonal picture of female athletes’ amenorrheas, like those of functional hypothalamic amenorrheas in general, appears to be characterized by a subversion of the normal hypothalamic organization, which induces a functional deficit of the pituitary – ovarian axis. In fact, excessive physical exercise is understood by the body as a condition of stress, which influences the secretion of neuro-endocrine modulators with important alterations in the release of numerous factors, inducing hypogonadotropic hypogonadism.
In particular, there is a reduction in the levels of gonadotropins, an increase in the levels of prolactin, GH, ACTH, glucocorticoids and endorphins ; moreover and especially, there is a state of profound hypoestrogenism, due to poor ovarian function, with important repercussions on bone metabolism. Free androgen levels are increased following the condition of estrogen deficiency and decreased levels SHBG. TSH, T3 and T4 levels decreased._ Furthermore, these subjects have low levels of leptin, a hormone produced by adipose tissue, which is decreased due to the reduction of fat mass. Finally, the persistence of the stress condition involves the activation of the hypothalamic-pituitary-adrenal axis and consequently high levels of cortisol.
In women who have not had a menstrual cycle for at least 3 months, as revealed by the careful anamnesis conducted by the specialist, it will first of all be necessary to evaluate the levels of FSH and estradiol, to differentiate between hypogonadotropic and hypergonadotropic hypogonadism ; in the case of amenorrhea in female athletes there will be a state of hypogonadotropism. To exclude a condition of hypothyroidism or hyperprolactinaemia, it will be necessary to proceed with the evaluation of thyroid hormones and prolactin.
The diagnostic process of amenorrhea in female athletes
At this point in the diagnostic process, it is essential to establish whether it is amenorrhea related to hypothalamic or pituitary dysfunction.
GnRH test
For this purpose, the GnRH test will be carried out, with single bolus administration or microinfusion. In the case of single bolus infusion, the GnRH is infused intravenously at a dose of 100 ug, evaluating the response of the gonadotropins by means of blood samples taken 15 minutes apart from each other, for 2 hours. In normal subjects the levels of LHthey will rise to their maximum values approximately 30 minutes after the start of the test; FSH levels will also be elevated, although less markedly than LH. In the microinfusion GnRH test, on the other hand, GnRH is administered at doses of 0.2-0.4 ug/min for 3 hours intravenously, with an evaluation of the gonadotropin response every 15 minutes.
In the event that no response of LH and FSH to the test is observed, hypogonadism will be due to a pituitary deficit, while, in the case of amenorrhea in female athletes, the response to the test will be normal, since it is a hypothalamic pathogenesis. To identify whether hypothalamic amenorrhea is functional, such as that caused by excessive physical exercise, it will be necessary to exclude possible central organic causes through instrumental tests.
Naloxone test
As a last diagnostic step, the naloxone test will be performed. Naloxone is a selective antagonist of opioid peptides and is administered intravenously as a single bolus dose of 2 mg, with the determination of LH levels every 15 minutes for 2 hours. In women with hypothalamic amenorrhea, the administration of naloxone will lead to an increase in LH levels, but not the characteristic peak which, on the other hand, is found in normal subjects.
Therapeutic procedure for amenorrhea in female athletes
The therapeutic approach makes use first of all of the removal of the cause that induced the alteration; it is therefore necessary to advise women to reduce physical activity, together with a recovery of body weight accompanied by a balanced diet. This approach allows, in most cases, the resolution of the problem.
Given the key role played by endogenous opioids in hypothalamic amenorrhea, the oral administration of naloxone is recommended for 3-6 months at a dose of 50 mg/day; usually, the results of this approach are good, especially in women who had shown, during the diagnostic assessment, a positive response to the naloxone test.
Pulsatile GnRH could be used for therapeutic purposes, administered by means of infusion pumps; in reality this approach is reserved for women wishing to become pregnant in order to cause the LH peak to induce ovulation. The use of oral contraceptives, if on the one hand it has the advantage of favoring the appearance of menstrual-like bleeding in the patient with amenorrhea due to excessive physical exercise, on the other hand it could induce in the patient herself the erroneous belief that she has healed, distracting his already scant attention to his state of health.
From what has been discussed in this article, it can be seen that the systemic repercussions that can occur in the event of excessive physical exercise are many and documented, and that the cessation or reduction of physical activity, in most cases, allows for the re -establishment of normal physiology. of the hypothalamic-pituitary- ovarian axis.
It is also indisputable that moderate physical activity brings significant benefits on health in general and reduces the risk of developing obesity and related pathologies, such as cardio-vascular and metabolic alterations.
Furthermore, moderate physical activity is able not only to regulate the menstrual cycle but also to improve a woman ‘s fertility.
