Menopause and hormone replacement therapy: the 2017 Recommendations of the Italian Menopause Society.

Over the last decade, the risk benefits ratio of hormone replacement therapy (HRT) has been reevaluated mainly in tens of cardiovascular risk. Present Consensus Statement is largely inspired by the Global Consensus on Menopausal Hormone Therapy in 2013 and 2016 by leading global menopause societies (The American Society for Reproductive Medicine, The Asia Pacific Menopause Federation, The Endocrine Society, The European Menopause and Andropause Society, The International Menopause Society, The International Osteoporosis Foundation and The North American Menopause Society). The aim of these recommendations is to provide a simple and updated reference on postmenopausal HRT. The term HRT typically includes estrogen replacement therapy (ERT) and estrogen-progestogen therapy (EPT). EPT can be sequential, when progestogen is added to ERT for 10-14 days a month, or continuous combined when progestogen is administered continuously every day along with a fixed amount of estrogen, In the everyday language, HRT includes also tibolone and the tissue-selective estrogen complex.

IRIS: methodological assessment of psychopathological disease in a cohort of hirsute women.

BACKGROUND: Hirsutism in females can be a source of considerable psychological distress and a threat to female identity. The aim of our study was to evaluate a possible relationship between facial, total body hair involvement and physical, mental and social well-being during 12 months of follow-up and treatment. Both objective and subjective methods of evaluating hirsutism were used: the Ferriman-Gallwey (FG) scoring method and the questionnaires General Health Questionnaire (GHQ)-12, Polycystic Ovary Syndrome Questionnaire (PCOSQ) and SF-12. METHODS: The total of 469 female patients (mean age 27.61±7.63 years) was enrolled in 27 Italian centers participating in this study. Higher total body score was correlated to significant emotional discomfort. The correlation between the FG total body score, the facial score and physical/mental health was found to be significant in all the patients assessed by SF-12 questionnaire. The ongoing reduction of GHQ-12 score was found for the facial FG score at the first follow-up (T0-T1 period) and at the second one (T0-T2). No relationship was found between T1 and T2. At both 6 (T1) and 12 months (T2) follow-up an increase of PCOSQ Score (psychological improvement) was accompanied by a concomitant reduction of the FG Score (reduction of hirsutism). Physical health assessed by SF-12 questionnaire does not change at both 6- and 12-month follow-up, but mental health decreased at both T1 and T2. RESULTS: The clinical improvement was achieved at 6 months regardless on treatment used and it was maintained for the next six-month follow-up. The clinical outcome could be assessed both by FG Score both through questionnaires administrated to each patient with hirsutism. CONCLUSIONS: For the evaluation of psychopathological discomfort the most appropriate questionnaire was GHQ-12, because of it major sensitivity to identify the psychological discomfort in the hirsutism.

Psychopathological traits of adolescents with functional hypothalamic amenorrhea: a comparison with anorexia nervosa.

BACKGROUND: Functional hypothalamic amenorrhea (FHA) is a form of anovulation, due to the suppression of hypothalamic-pituitary-ovarian axis, not related to identifiable organic causes. Like adolescents with anorexia nervosa (AN), subjects with FHA show dysfunctional attitudes, low self-esteem, depressive mood, anxiety and inability to cope with daily stress. The aim of the study is to examine similarities and differences between FHA and AN in terms of clinical profiles and psychological variables. METHODS: 21 adolescents with FHA, 21 adolescents with anorexia nervosa, and 21 healthy adolescents were included in the study. All the teenagers completed a battery of self-administered psychological tests for the detection of behaviors and symptoms attributable to the presence of an eating disorder (EDI-2), depression (CDI), and alexithymia (TAS-20). RESULTS: Different from healthy controls, subjects with FHA and with AN shared common psychopathological aspects, such as maturity issues, social insecurity and introversion, a tendency to depression, excessive concerns with dieting, and fear of gaining weight. Nevertheless, adolescents with AN presented a more profound psychopathological disorder as observed at test comparisons with subjects with FHA. CONCLUSIONS: Results show a clinical spectrum that includes AN and FHA and suggest the necessity to treat FHA with a multidisciplinary approach for both organic and psychological aspects.

Heart rate variability in adolescents with functional hypothalamic amenorrhea and anorexia nervosa.

Aim of this study consisted in assessing the 24-h heart rate variability (HRV), a measure of autonomic nervous system (ANS) imbalance, in 21 adolescents with functional hypothalamic amenorrhea (FHA, 11 normogonadotropic, N-FHA, and 10 hypogonadotropic, Hy-FHA) compared to 21 patients with anorexia nervosa (AN) and 21 controls. As expected, subjects with AN showed a significant dysregulation in multiple HRV parameters, while Hy-FHA patients presented with a dysregulation in a few domains (SDNN, HFr), which was not present in girls with N-FHA, who showed values largely similar to controls. FHA might represent part of the AN biological spectrum, and a link between these two conditions might exist, possibly related to the degree of psychological and/or hormonal dysfunction.

Spermatogenic and steroidogenic impairment of the testicle characterizes the hereditary leucine-75-proline apolipoprotein a-I amyloidosis.

CONTEXT: The leucine-75-proline variant of apolipoprotein A-I leads to a new hereditary systemic amyloidosis involving mostly the liver and kidney. OBJECTIVE: The objective of the study was to examine the effects of this amyloidosis on testicular structure and function. DESIGN: This was an observational study in which patients with testicular amyloidosis were characterized. SETTING: The study was carried out at the Endocrinology Department of Brescia University. PATIENTS OR OTHER PARTICIPANTS: Over a 13-yr period, 25 patients were found to be affected by leucine-75-proline apolipoprotein A-I testicular amyloidosis. Thirteen had the testicle as the first or only organ involved (group 1); in 12 testicular damage followed that of other organs (group 2). INTERVENTIONS: There were no interventions. MAIN OUTCOME MEASURE: Hormone and lipidic profiles, semen analysis, echographic volume of testicles, testicular histology, and genetic analysis were carried out. RESULTS: Group 1 patients were younger than those of group 2. In group 1, eight had hypergonadotropic hypogonadism and five were normogonadic with high gonadotropins; in group 2 all subjects were hypogonadic. All men had low high-density lipoprotein values. Group 1 patients were macroorchid, whereas the testicular volume was at the highest limit in group 2 (group 1 vs. group 2, P < 0.05). All men in the first group and six in the second group were azoospermic; the remaining had oligoposia. Biopsies showed the germinal epithelium replaced by amyloid. Leydig cells were essentially preserved in normogonadic but not hypogonadic patients. CONCLUSIONS: This amyloidosis may determine infertility, macroorchidism, and hypogonadism. Endocrine impairment follows spermatogenic impairment.

Endocrine profiles and neuropsychologic correlates of functional hypothalamic amenorrhea in adolescents.

OBJECTIVE: To determine trigger factors and neuropsychologic correlates of functional hypothalamic amenorrhea (FHA) in adolescence and to evaluate the correlations with the endocrine-metabolic profile. DESIGN: Cross-sectional comparison of adolescents with FHA and eumenorrheic controls SETTING: Academic medical institution PATIENT(S): Twenty adolescent girls with FHA (aged <18 years) and 20 normal cycling girls INTERVENTION(S): All subjects underwent endocrine-gynecologic (hormone) and neuropsychiatric (tests and interview) investigations. A separate semistructured interview was also used to investigate parents. MAIN OUTCOME MEASURE(S): Gonadotropins, leptin, prolactin, androgens, estrogens, cortisol, carrier proteins (SHBG, insulin-like growth factor-binding protein 1), and metabolic parameters (insulin, insulin-like growth factor 1, thyroid hormones) were assayed in FHA and control subjects. All girls were evaluated using a test for depression, a test for disordered eating, and a psychodynamic semistructured interview. RESULT(S): Adolescents with FHA showed a particular susceptibility to common life events, restrictive disordered eating, depressive traits, and psychosomatic disorders. The endocrine-metabolic profile was strictly correlated to the severity of the psychopathology. CONCLUSION(S): Functional hypothalamic amenorrhea in adolescence is due to a particular neuropsychologic vulnerability to stress, probably related to familial relationship styles, expressed by a proportional endocrine impairment.

Androgens, insulin-like growth factor-I (IGF-I), and carrier proteins (SHBG, IGFBP-3) in postmenopause.

OBJECTIVE: To determinate the profile of androstenedione (A), total (T), and free testosterone (FT), dehydroepiandrosterone (DHEA), DHEA-sulphate (DHEAS), sex hormone-binding globulin (SHBG), insulin-like growth factor-I (IGF-I) and IGF-binding protein-3 (IGFBP-3) in non-smoking, postmenopausal women of normal weight and to search for correlations between hormones and carrier proteins and chronological age, number of years of postmenopause and age of onset of menopause. DESIGN: A group of 149 postmenopausal women aged 49 to 74 years were divided into three groups based on the number of years of postmenopause: 2-4 years (group A), 9-12 years (group B), and 19 years or more (group C). Seventy-two women aged 21 to 35 years were the controls. Hormones and carriers were assessed in all groups. RESULTS: A, DHEA, DHEAS, and IGF-I were significantly lower than controls in all groups, whereas T, FT, SHBG, and IGBFP-3 were lower only in groups B and C. All hormones and carriers were negatively correlated with the number of years of postmenopause; DHEA and T also showed a positive correlation with the age of onset of menopause. CONCLUSIONS: Androgens, SHBG, and IGF-I/IGFBP-3 show a diversified decline in postmenopause that is involved in the physiological aging process. Thus, a modification, in excess or deficiency, could favor the development of central symptoms or pathologies.

Leptin in functional hypothalamic amenorrhoea.

BACKGROUND: Leptin, body weight, body mass index (BMI) and other hormones in women with functional hypothalamic amenorrhoea (FHA) were investigated and the hypothesis proposed that energy imbalance is the predominant mechanism for leptin reduction in patients with FHA. METHODS: Eighty-eight women with FHA and 65 age- and weight-matched controls were divided into homogeneous groups on the basis of their BMI: women with different degrees of underweight (BMI 15-16, 17-18 kg/m(2)) and of normal weight (BMI 19-21, 22-24 kg/m(2)). Hormone and carrier protein assays were measured in all groups. RESULTS: In each BMI group of patients with FHA, gononadotrophins, prolactin, insulin, free tri-iodothyronine and leptin levels were significantly lower than those of the respective controls, whereas cortisol and insulin-like growth factor (IGF)-binding protein-1 (IGFBP-1) were higher. We found significant linear positive correlations between leptin and body weight, BMI, LH, peptide-C, insulin, IGF-1 values and negative correlations with cortisol and IGFBP-1. CONCLUSIONS: Leptin values in women with FHA are significantly lower than controls, even in the group of patients having normal body weight and BMI. Leptin profile is different between patients with FHA and controls: it is suggested that energy balance can interfere with the ratio of body weight/leptin and BMI/leptin in FHA.

Long-term follow-up of functional hypothalamic amenorrhea and prognostic factors.

This study evaluated the prognosis of functional hypothalamic amenorrhea (FHA) and the predictive factors of recovery, through a long-term follow-up. Ninety-three women affected by FHA underwent a follow-up for an average period of 8.1 yr (range 7-9 yr). At the end of the follow-up, 65 (70.7%) patients recovered. Statistical analysis showed that there was no association between recovery and anamnestic causes of FHA or with the echographic ovarian morphology but identified the predictive factors of recovery as the basal body mass index (BMI), the basal cortisol, and androstenedione plasma levels. A higher basal BMI and A, and lower cortisol values are positive prognostic factors for the recovery. Also the BMI, acquired during the follow-up, is important for FHA resolution: in fact, in recovered women the BMI increased or remained stable, whereas in nonrecovered women it decreased or remained stable. At the end of the follow-up, 52 (74.3%) patients treated with hormone replacement therapy and 8 (80%) with no therapy recovered, but only 5 (41.7%) with oral contraceptive pills recovered.