Impaired Sexual Function in Young Women With PCOS: The Detrimental Effect of Anovulation.

BACKGROUND: Even though polycystic ovary syndrome (PCOS) is a common reproductive disorder affecting young women, its impact on their sexual health is not well known. AIM: To examine the different aspects of female sexuality in young women with PCOS and attempt to associate hormonal changes and ovulatory status with their sexual function. METHODS: Anthropometric characteristics, hormonal levels and sexual function based on the Female Sexual Function Index (FSFI) questionnaire were assessed in 76 young women with PCOS and 133 matched controls. OUTCOMES: Sexual function is significantly impaired in young women with PCOS. RESULTS: Women with PCOS demonstrated lower scores than controls in arousal (5.04 ± 1.19 vs 4.48 ± 1.44, P < .001), lubrication (5.29 ± 1.17 vs 4.69 ± 1.54, P < .001), orgasm (4.78 ± 1.40 vs 4.11 ± 1.61, P = .001), satisfaction (5.22 ± 1.10 vs 4.78 ± 1.31, P = .016), and total score of the FSFI (29.51 ± 5.83 vs 26.76 ± 6.81, P < .001), even after correction for BMI. When corrected for total testosterone, the domains of lubrication, satisfaction, and total score of FSFI remained significantly impaired in women with PCOS (P values .037, .024, & .044 respectively). In multivariate logistic regression analysis, after adjusting for the effect of BMI and hormone levels, dysfunction in orgasm, satisfaction and the total FSFI score were still 3-4 times more common in PCOS (adjusted OR [95% CI]: 3.54, P = .020; 2.96, P = .050; 3.87, P = .027). Even though no statistically significant differences were observed between women with ovulatory PCOS and controls, we detected statistically significant differences in all domains of sexual function apart from pain between controls and PCOS women with anovulation (desire P value .04, arousal P value <.001, lubrication P value <.001, orgasm P value .001, satisfaction P value .001 and FSFI total score P value <.001). CLINICAL IMPLICATIONS: Women with PCOS have compromised sexual function, which is independent of their BMI and highly dependent on their ovulatory status. STRENGTHS AND LIMITATIONS: This is the first study in women with PCOS that implicates anovulation as a risk factor for sexual impairment in PCOS. Further studies are needed to elucidate the mechanisms implicated and to examine the effect of PCOS therapy on the patients' sexual function. CONCLUSION: The adverse effect of PCOS status on the female sexual function is independent of BMI and only partially dependent on hormonal changes characterizing the syndrome. Anovulation appears to be the major determinant of sexual impairment among women with PCOS. Mantzou D, Stamou MI, Armeni AK, et al. Impaired Sexual Function in Young Women With PCOS: The Detrimental Effect of Anovulation. J Sex Med 2021;18:1872-1879.

Effect of excess iodine intake on thyroid on human health.

The recommended daily intake of iodide, is 150 µg for adolescents and adults, 250 µg for pregnancy and lactation. Thyroid gland is an effective collector of iodine. The active iodine uptake along the basolateral membrane of thyroid cell is followed by its transport to the apical edge of the cell and then to the follicle lumen. TSH acts through cAMP and stimulates NIS gene expression and protein synthesis. The major proportion of iodine in the thyroid gland is bound to Thyroglobulin. The non-organic intrathyroidal iodine is usually low, but significantly greater compared to plasma. Large doses of iodine reduce both the uptake and the organification (Wolff-Chaikoff effect) and cause partial inhibition of Tg proteolysis. The thyroid gland has several protective mechanisms resulting on the maintenance of normal thyroid function despite wide fluctuations of the daily iodine intake. Ingestion of several commonly used drugs and food conservatives results in acute or chronic excessive iodine intake. Failure to escape from the iodine induced organification inhibition can cause hypothyroidism, which is temporary and subsides after iodine exposure ceases. Iodine excess may also establish a status of excessive thyroid hormone synthesis and release, thus inducing autonomic thyroid function in iodopenic areas or can contribute to the development of iodine-induced hyperthyroidism in iodine abundant areas. The anti-arrhythmic Amiodarone, is a benzofuranic product with a very high iodine content, is associated with either hypo- or hyperthyroidism development. In the presence of defective auto-protective mechanisms, excessive iodine ingestion can divert the normal thyroid function.

Low-risk papillary thyroid carcinoma patients who underwent near-total thyroidectomy without prophylactic central compartment lymph node dissection and were ablated with low-dose 50mCi RAI had excellent 10-year prognosis.

BACKGROUND: The current trend in the management of low risk differentiated thyroid carcinoma is to follow less aggressive strategies. OBJECTIVE: To assess the long-term morbidity and mortality outcomes of low-risk papillary thyroid carcinoma (PTC) patients undergoing minimal intervention. DESIGN: We retrospectively analyzed 137 patients with low-risk PTC (stage I: n=77; stage II: n=60). Of these patients, 107 (Group 1) had macro-PTC and underwent near-total thyroidectomy and received postoperatively 50mCi RAI. The remaining 30 patients (Group 2) had micro-PTC (<1cm) and were treated only by means of near-total thyroidectomy. RESULTS: The median follow-up for Group 1 patients was 10 years (range: 3-30). At 1-year evaluation, 8 patients of Group 1 had indeterminate or incomplete biochemical response, of whom 4 had also incomplete structural response to initial therapy. Only 1 of 4 patients with structural incomplete response underwent cervical lymph node dissection and then received an additional dose of 100mCi RAI. The remaining 7 patients received only an additional dose of 100mCi RAI. These patients have been continuously followed till the present time with no recurrences or deaths (median follow-up: 17.5 years; 3-30 years). At 15 years, 2 patients of Group 1 experienced biochemical recurrence and they received 100mCi RAI. Three patients of Group 2 experienced recurrence, with 2 receiving 50mCi RAI and 1 undergoing cervical lymph node dissection with 50mCi RAI. CONCLUSIONS: Patients with low-risk macro-PTC treated by means of near-total thyroidectomy without PCCLND and receiving postoperatively a low dose of 50mCi RAI have excellent long-term prognosis.

Association of Calpain (CAPN) 10 (UCSNP-43, rs3792267) gene polymorphism with elevated serum androgens in young women with the most severe phenotype of polycystic ovary syndrome (PCOS).

OBJECTIVES: To highlight a possible association of Calpain (CAPN 10) gene UCSNP-43 polymorphism with hormonal and metabolic traits of young women with different phenotypes of polycystic ovary syndrome (PCOS). DESIGN: PCOS women were genotyped for the CAPN 10 gene UCSNP-43 polymorphism. A comparison of clinical and biochemical features of women with PCOS stratified on the basis of the CAPN 10 gene UCSNP-43 variants was assessed. METHODS: Anthropometric, hormonal and biochemical measurements were carried out in 668 PCOS women and 200 healthy controls. Subjects were also genotyped for the CAPN 10 gene UCSNP-43 polymorphism. The genotype frequency distributions between groups and controls were compared using the chi-square test. The association of the polymorphism with the clinical and biochemical features of the study cohort was estimated as well. RESULTS: No association of the frequency of CAPN 10 gene UCSNP-43 polymorphism with PCOS was detected. No association of the polymorphism with the anthropometric, biochemical and hormonal features was detected both in PCOS and control women. The polymorphism was associated with serum Δ4 androstenedione (p = 0.018), as well as with 17-OH progesterone (17-hydroxyprogesterone) among women with PCOS phenotype A (p = 0.012). CONCLUSIONS: CAPN 10 gene polymorphism UCSNP-43 is deprived of a metabolic contribution to cardiovascular disease (CVD). However, due to its association with androgen excess in phenotype A, CAPN 10 gene polymorphism UCSNP-43 could be used as a genetic marker for CVD in young PCOS women.

Elevated serum androstenedione is associated with a more severe phenotype in women with polycystic ovary syndrome (PCOS).

OBJECTIVE: To evaluate the impact of elevated serum Δ4A levels on the hormonal and metabolic features of the different phenotypes of PCOS. DESIGN: 1276 women with PCOS according to the Rotterdam criteria were included, in whom serum hormonal levels were determined. RESULTS: In PCOS women as a whole, as well as in patients presenting clinical and/or biochemical hyperandrogenemia (phenotypes I and II), Δ4A levels >3.8 ng/ml were positively related to LH, LH/FSH ratio, T, DHEAS, 17 OH progesterone and FAI and negatively related to T/Δ4A ratio. In the milder phenotype III, a positive correlation between Δ4A levels >3.8 ng/ml and T, DHEAS, 17 OH progesterone and FAI and a negative one between increased Δ4A and T/Δ4A ratio were reported. In the whole PCOS group with androstenedione >3.8 ng/ml, an increased ovarian volume was observed, while a greater mean follicular number was found only in phenotypes I and II. CONCLUSIONS: Increased serum Δ4A levels, which are associated with more severe PCOS phenotypes, possibly contribute to the worsening of PCOS features and therefore could be a valuable marker of biochemical hyperandrogenemia.

Salivary adiponectin levels are associated with training intensity but not with bone mass or reproductive function in elite Rhythmic Gymnasts.

Elite Rhythmic Gymnasts (RGs) constitute a unique metabolic model and they are prone to developing Anorexia Athletica. The aim of the present study was to evaluate the effect of training intensity on salivary adiponectin levels and assess a possible role of salivary adiponectin levels as a predictive factor of reproductive dysfunction and bone mass acquisition in elite RGs. The study included 80 elite female RGs participating in the World Rhythmic Gymnastics Championship tournament held in Montpellier, France on September 2011. Anthropometric values were assessed, training data and menstrual pattern were recorded, bone mass was measured with Broadband ultrasound attenuation (dB/Mhz) and baseline salivary adiponectin levels were determined. The athletes were classified as intensely and very intensely trained, considering the mean training intensity (40.84h/week). Moreover, considering their reproductive status, they were divided into RG's with normal menstruation, primary amenorrhea and oligomenorrhea. All comparisons were adjusted to age, BMI and body fat percentage differences. Very intensely trained RGs showed higher salivary adiponectin levels (p=0.05). Moreover, salivary adiponectin levels showed significant correlation with training intensity (r=0.409, p=0.003). On the other hand, no association of salivary adiponectin levels was documented with either reproductive function or bone mass acquisition. The results of the present study suggest that, in elite RGs, salivary adiponectin levels are associated with the intensity of training, possibly reflecting the deterioration of energy balance rather than the training stress. On the other hand, a predictive role of salivary adiponectin levels in reproductive dysfunction or bone mass acquisition could not be supported.

Despite a high prevalence of menstrual disorders, bone health is improved at a weight-bearing bone site in world-class female rhythmic gymnasts.

CONTEXT: Regular physical activity during puberty improves bone mass acquisition. However, it is unknown whether extreme intense training has the same favorable effect on the skeleton. OBJECTIVE: We evaluated the bone mass acquisition in a unique cohort of world-class rhythmic gymnasts. STUDY PARTICIPANTS: A total of 133 adolescent girls and young women with a mean age of 18.7 ± 2.7 (14.4-26.7) years participated in this study: 82 elite rhythmic gymnasts (RGs) and 51 controls (CONs). MAIN OUTCOME MEASURES: Anthropometric variables and body composition were assessed, and all participants completed questionnaires on their general medical, menstrual, and training histories. Broadband ultrasound attenuation (BUA in decibels per megahertz) was determined by quantitative ultrasound at the heel. RESULTS: RGs presented lower weight (-8.5%, P < .001), body mass index (-11.7%, P < .001), and body fat mass (-43%, P < .001) and higher muscle mass (6.3%, P < .01) and height (+2.8 cm, P < .01). RGs presented an age of menarche significantly delayed compared with CONs (15.6 ± 1.6 vs 12.7 ± 1.7 years; P < .001) and a high prevalence of menstrual disorders (64%). BUA values were higher in RGs vs CONs (68.6 ± 4.6 and 65.4 ± 3.3 dB/Mhz, respectively; P < .001). This difference was exacerbated when BUA was adjusted for age and body weight. BUA values in RGs were not affected by menstrual or training status. Among RGs with menarche, BUA was higher (71.5 ± 4.1 and 67.9 ± 3.5 dB/Mhz) for delayed (14.4 ± 0.8 years) vs severely delayed (17.3 ± 1.4 years) menarcheal age. BUA was positively correlated with body weight and body mass index and tended to be correlated with age. CONCLUSION: Conversely to expectations for adolescents and young women with a high prevalence of menstrual disorders and/or delayed menarche, intense training in rhythmic gymnastics appeared to have a beneficial effect on the bone health of a weight-bearing site. This effect was nevertheless modulated by the age of menarche. The high mechanical loading generated by this activity may counterbalance the negative effect of menstrual disorders.

The effect of prolonged aerobic exercise on serum adipokine levels during an ultra-marathon endurance race.

OBJECTIVE: To evaluate the effect of prolonged intensive aerobic exercise and acute energy deficit (180 km ultra-marathon race) on serum leptin, adiponectin, resistin and visfatin levels and their association and interaction with serum cortisol and insulin levels in highly trained ultra-endurance runners. DESIGN: The study included 17 highly trained ultra-endurance male athletes (mean age 51.29±6.84 years and body mass index (ΒΜΙ) 23.51±1.90) participating in the 5th Olympian Race held in Greece on May 2010. Anthropometric values were assessed; Serum cortisol, insulin, leptin, adiponectin, resistin and visfatin levels were measured at baseline, post-exercise and ~20 hours after the end of the race. RESULTS: All hormonal values of the post-exercise and recovery status were corrected for plasma volume changes. The estimated energy deficit during the ultra-endurance event was about 5000 Kcal. At the end of the race serum resistin levels were elevated (p<0.001) and serum leptin levels were reduced (p<0.001) and failed to reach pre-exercise levels, although showing a tendency towards restoration. No significant changes were noted in serum adiponectin and visfatin levels. CONCLUSIONS: Ultra-endurance aerobic exercise and acute negative energy balance lead to an up-regulation of serum resistin levels and a down-regulation of serum leptin levels.

Increased frequency of the anti-mullerian-inhibiting hormone receptor 2 (AMHR2) 482 A>G polymorphism in women with polycystic ovary syndrome: relationship to luteinizing hormone levels.

CONTEXT: The polycystic ovary syndrome (PCOS) is a common and complex disease without a clear pattern of inheritance. Anti-Müllerian hormone (AMH) has an inhibitory effect on FSH-stimulated follicle growth. Serum AMH levels are higher in women with PCOS than in normo-ovulatory women. The elevated AMH levels may reflect abnormalities in AMH signaling. OBJECTIVE: The purpose of this study was to evaluate the association of the anti-Müllerian hormone receptor 2 (AMHR2) -482 A>G polymorphism (rs2002555) with the pathophysiology of PCOS. DESIGN: AMHR2 -482 A>G polymorphism genotyping were performed in a large cohort of women with PCOS and in a healthy control group. SETTING/SUBJECTS: A total of 858 Caucasian Greek women with PCOS and 309 healthy control women were studied. INTERVENTIONS: Genotyping and hormonal measurements were preformed. MAIN OUTCOME MEASURES: Hormone levels in women with PCOS were analyzed. RESULTS: The AMHR2 polymorphism was more common in women with PCOS than in control women (P = .026). Homozygous AMHR2 -482 A>G gene polymorphisms (GG) were associated with decreased levels of LH (P = .003) and lower LH to FSH ratios (P = .01) in women with PCOS, as well as with lower prolactin levels (P = .004). No other associations related to AMHR2 -482 A>G polymorphisms were observed in women with PCOS or control women. CONCLUSION: In this study, the role of the AMHR2 -482 A>G gene polymorphism in the pathogenesis of PCOS was suggested by the association of the variant with PCOS risk. Thus, further research is needed to elucidate a possible association of the AMHR2 -482 A>G gene polymorphism with AMH signaling and impaired ovarian function and its clinical significance in women with PCOS.

Diet, physical exercise and Orlistat administration increase serum anti-Müllerian hormone (AMH) levels in women with polycystic ovary syndrome (PCOS).

The present study investigates the combined effect of diet, physical exercise and Orlistat for 24 weeks, on serum anti-Müllerian hormone (AMH) levels in overweight and obese women with polycystic ovary syndrome (PCOS) and in overweight and obese controls. Sixty-one (61) selected women with PCOS and 20 overweight and obese controls followed an energy-restricted diet, physical exercise plus Orlistat administration (120 mg, 3 times per day) for 24 weeks. At baseline, week 12 and week 24, serum levels of AMH, FSH, LH, PRL, androgens, sex hormone-binding globulin (SHBG), glucose, and insulin were measured and Free Androgen Index (FAI) and Insulin Resistance (IR) indices were calculated. In PCOS women, serum AMH levels increased after 12 and 24 weeks of treatment. After 12 weeks LH and SHBG were increased, while Testosterone decreased. After 12 and 24 weeks, FAI was decreased and all indices of IR were significantly improved. We concluded that in overweight and obese women with PCOS Orlistat administration, combined with diet and physical exercise, for 24 weeks, resulted in significant weight loss, improvement of hyperandrogenism and insulin sensitivity, and increased serum AMH levels.

Final height in elite male artistic gymnasts.

OBJECTIVE: Elite male artistic gymnasts (AG) are exposed to high levels of physical and psychological stress during adolescence and experience a significant late maturation in both linear growth and pubertal development. The aim of the present study was to determine the impact of intensive physical training on the adult final height in elite male AG. METHODS: This study is unique in character, as all variables were measured on the field of competition. The study was prospective and longitudinal; however, the current analysis of data is cross-sectional. Data from 86 elite male AG were obtained during the gymnastics competitions of European and World Championships. Clinical evaluation included height and weight measurements, as well as assessment of pubic hair and genital development according to Tanner's stages of pubertal development. The laboratory investigation included determination of skeletal maturation. All athletes completed a questionnaire that included questions on personal (onset and intensity of training, number of competitions per year) and family data (paternal and maternal heights). RESULTS: Male AG were below the 50th percentile for both final height and weight. Elite male AG had final height standard deviation score (SDS) lower than their genetic predisposition. Final height SDS was correlated positively with target height SDS (r = 0.430, p < 0.001) and weight SDS (r = 0.477, p < 0.001) and negatively to the intensity of training (r = -0.252, p = 0.022). The main factors influencing final height, by multiple regression analysis were weight SDS (p < 0.001) and target height SDS (p = 0.003). CONCLUSION: In elite maleAG, final height falls short of genetic predisposition, still well within normal limits. Considering medical and psychological risks in general, and based on the results of this research project, the International Federation of Gymnastics has increased the age limit for participants in international gymnastics competitions by 1 year.

Sibutramine administration decreases serum anti-Müllerian hormone (AMH) levels in women with polycystic ovary syndrome.

OBJECTIVE: To investigate the effect of diet, physical exercise and sibutramine administration on serum anti-Müllerian hormone (AMH) levels, hormonal and metabolic parameters in overweight and obese patients with polycystic ovary syndrome (PCOS). STUDY DESIGN: Prospective clinical study, in an outpatient clinic setting, of 76 overweight and obese women with PCOS. All patients were placed on a hypocaloric diet, physical exercise plus sibutramine (10 mg per day) for the first month and then on either a hypocaloric diet, physical exercise plus sibutramine (10 mg per day) or a hypocaloric diet and physical exercise for the subsequent 6 months. Serum AMH levels, body composition, hormonal and metabolic features and insulin sensitivity indices were evaluated at baseline and at 4 and 7 months of treatment. RESULTS: Body weight reduction was greater in the sibutramine group. Moreover, serum FSH and testosterone levels decreased, and SHBG, free androgen index and all indices of insulin resistance significantly improved at 4 and 7 months. Serum AMH levels decreased only in PCOS women who received sibutramine, at both 4 and 7 months of treatment. CONCLUSION: A hypocaloric diet and a diet plus sibutramine both resulted in significant weight loss in overweight and obese women with PCOS. Patients who received sibutramine showed greater weight loss and improvement in hyperandrogenemia and insulin sensitivity after 7 months of treatment. Serum AMH levels significantly decreased at both 4 and 7 months of treatment only in PCOS women who received sibutramine, indicating a possible direct, gonadotropin independent effect of sibutramine on the ovarian production of AMH.

Increased frequency of the DI genotype of the angiotensin-I converting enzyme and association of the II genotype with insulin resistance in polycystic ovary syndrome.

OBJECTIVE: The polycystic ovary syndrome (PCOS) is a common and complex disease with unclear pattern of inheritance, characterized by an androgen excess, while hyperinsulinemia and insulin resistance (IR) are common features of the syndrome. The angiotensin I converting enzyme (ACE) insertion (I)/deletion (D) gene polymorphism was proved to be involved in many pathophysiological conditions, including hypertension and IR. DESIGN: The purpose of this study was to evaluate the involvement of the ACE gene polymorphism in the pathogenesis of PCOS. METHODS: In a case-control association study involving 801 PCOS women and 266 healthy controls, hormonal determinations and ACE polymorphism genotyping were performed. The PCOS women were classified into three groups: Group A presented biochemical hyperandrogenism, combined with anovulation and polycystic ovarian morphology; Group B, clinical hyperandrogenism combined with anovulation and polycystic ovarian morphology; and Group C, chronic anovulation and polycystic ovarian morphology. RESULTS: A significant increase in the frequency of the DI genotype of the ACE polymorphism was detected in PCOS women as a whole (P=0.035), in PCOS Group A (P=0.039) and Group B (P=0.010), while there was no difference in Group C (P=0.939). Significant difference was also observed in hyperandrogenic PCOS women as a whole (Group A+B) (P=0.017). The II genotype was positively correlated with HOMA-IR and QUICKI and with fasting insulin and glucose/insulin ratio in these groups. CONCLUSIONS: The association study of the ACE I/D polymorphism in PCOS women demonstrates an increase in the DI genotype incidence and an association of the II genotype with IR.

Measurement of salivary resistin, visfatin and adiponectin levels.

Hormonal determination in saliva offers several advantages. Peptides enter the salivary glands either by active transport mechanisms or are expressed and secreted by the salivary glands themselves. The collection of saliva is a noninvasive, easily repeatable and less stressful technique than blood withdrawal. The purpose of the present study was to introduce a method for measuring salivary resistin, visfatin and adiponectin levels and to evaluate their associations with serum levels. Resistin, visfatin and adiponectin levels were measured in serum and saliva of 50 healthy adult volunteers (17 male and 33 female) using commercial enzyme immunoassay kits for serum with minor modifications. The present study documented the determination of resistin and adiponectin levels in saliva and the significant correlation of salivary levels with serum levels (r=0.441, p<0.01 and r=0.347, p<0.05, respectively). Moreover, the identification of visfatin in saliva was achieved, but no significant correlation with serum visfatin levels was observed. To our knowledge, this is the first study to report the determination of resistin and visfatin in saliva and the significant correlation of salivary resistin with serum levels, while it confirmed the significant association between salivary and serum adiponectin. The introduction of salivary determinations of adipokines could contribute to the elucidation of the physiology and the role of the specific adipokines in various clinical conditions (obesity, insulin resistance, inflammation, reproduction, energy imbalance and stress response).

Menstrual function in sports.

OBJECTIVE: To highlight the recent developments in the field of menstrual function in sports and to provide an overview of our current understanding in regard to the pathophysiology, evaluation and management strategies of exercise-related reproductive dysfunction. DESIGN: A PUBMED search was carried out and all articles published from 1980 to 2010 with title words related to exercise, athletes, menstrual function and primary and secondary amenorrhea were reviewed. The review structure includes a pathophysiology overview, menstrual dysfunction among different athletic disciplines, clinical manifestations, evaluation and management strategies, with particular emphasis on recent data regarding the use of oral contraceptives and hormone replacement therapy. RESULTS AND CONCLUSION: Exercise-related reproductive dysfunction appears to be multifactorial in origin and remains a diagnosis of exclusion. Recent findings underscore the endocrine role of adipose tissue in the regulation of metabolism and reproduction, providing further data on our understanding of the pathophysiology of exercise-related reproductive dysfunction. Clinical manifestations range from primary amenorrhea or delayed menarche to luteal phase deficiency, oligomenorrhea, anovulation and secondary amenorrhea. Amenorrhea constitutes the most serious clinical consequence and is associated with bone pathology. Early diagnosis, thorough evaluation and individualized management (ranging from diet and exercise, or behavior adjustments to pharmacologic treatment) should be achieved in order to preserve bone mass.

The influence of intensive physical training on growth and pubertal development in athletes.

Genetic potential for growth can be fully expressed only under favorable environmental conditions. Although moderate physical activity has beneficial effects on growth, excessive physical training may negatively affect it. Sports favoring restricted energy availability, in the presence of high energy expenditure, are of particular concern. In gymnastics, a different pattern in skeletal maturation and linear growth was observed, resulting in an attenuation of growth potential in artistic gymnasts (AG), more pronounced in males than in females. In female rhythmic gymnasts (RG), the genetic predisposition to growth was preserved owing to a late catchup growth phenomenon. In all other sports not requiring strict dietary restrictions, no deterioration of growth has been documented so far. Intensive physical training and negative energy balance alter the hypothalamic pituitary set point at puberty, prolong the prepubertal stage, and delay pubertal development and menarche in a variety of sports. In elite RG and AG, prepubertal stage is prolonged and pubertal development is entirely shifted to a later age, following the bone maturation rather than the chronological age.