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Background Almost half of patients with functional hypothalamic amenorrhea (FHA) show polycystic ovarian morphology (PCOM) on the ultrasound, which leads to a diagnostic confusion. Although FHA and polycystic ovarian syndrome (PCOS) have been thought to co-exist and some FHA-patients seem to have had PCOS before developing FHA, respectively, once hypothalamic inhibition proceeds, the FHA phenotype predominates over the PCOS features, except from PCOM. This connection has never been shown longitudinally. Furthermore, it is still not clear if FHA-PCOM is actually related to preexisting PCOS or if these women constitute their very own heterogeneous subgroup. Thus, the aims of this study were to evaluate changes in hormonal parameters and PCOM after remission and to provide further insight into pathophysiological processes of PCOM in FHA. Methods Monocentric retrospective cohort study. Sixty women with FHA in remission were included. While anti-mullerian hormone (AMH) was the main outcome parameter, we also analyzed total testosterone, luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol (E2), sex hormone-binding globulin (SHBG) and dehydroepiandrosterone sulfate (DHEAS). PCOM was diagnosed using ultrasound. Results At baseline, FHA-PCOM patients revealed higher baseline prolactin ( p  = 0.029) and AMH levels ( p  < 0.001). At follow-up, compared to women without PCOM, these women had higher PCOM prevalence (48.1% versus 0%, p  < 0.001), higher AMH levels (median 6.49 ng/mL, IQR 4.74–7.95 versus median 2.25 ng/mL, IQR 2.0-2.71; p  < 0.001) and higher PCOS prevalence (22.2% versus 0%, p  = 0.006). While overall median AMH levels increased significantly, FHA-PCOM patients revealed a significant median decrease in AMH levels (median AMH dynamics − 0.82 ng/mL, IQR – 2.30 - -0.16; p  < 0.001). Conclusions Our data support the hypothesis that relative FSH deficiency in hypothalamic dysfunction can lead to lower AMH levels. In contrast, the decline in AMH levels and the resolution of PCOM in the FHA-PCOM group may indicate a reversible state of ovarian hyperactivation during FHA. Trial registration Not applicable.

Background Women with functional hypothalamic amenorrhea (FHA) reveal polycystic ovarian morphology (PCOM) in up to 50%. If stress sensitivity in women with polycystic ovary syndrome (PCOS) is the reason why PCOS women are prone to develop FHA, patients with FHA caused by stress should reveal PCOM more often. Methods In a retrospective cohort study, 38 stress-associated and 38 excessive exercise-induced FHA women were included. The main outcome parameter was PCOM. In addition, the focus was on general patient characteristics as well as on prolactin, dehydroepiandrosterone-sulphate (DHEAS), and anti-Mullerian hormone (AMH). Results PCOM was found in 34/76 patients (44.7%). The stress group showed a higher prevalence of PCOM than the excessive exercise group (57.9% versus 31.6%, p =  0.019) as well as higher prolactin levels (median 13.2ng/mL versus 11.7ng/mL, p =  0.008) and a trend towards higher DHEAS levels ( p =  0.058). Conclusions In FHA women, the PCOM prevalence was significantly higher in the stress-group than in the excessive exercise-group. The well-known stress sensitivity in women with PCOS might explain why PCOS women are prone to develop FHA as well as the high PCOM prevalence in FHA women.

Saliva was proposed as a diagnostic tool for systemic diseases. Here we determined the correlation of bone turnover markers in saliva, bone turnover markers in serum and bone mineral density in postmenopausal osteoporotic and healthy women. Forty postmenopausal osteoporotic and 40 age-matched healthy non-osteoporotic females were recruited for this case–control study. Serum and stimulated saliva levels of osteocalcin, N-terminal propeptide of type I collagen, bone-specific alkaline phosphatase and cross-linked-C-telopeptide of type I collagen were determined. Bone mineral density of the lumbar spine, proximal femur, and total hip were obtained. We show that osteocalcin and cross-linked-C-telopeptide of type I collagen (CTX) reached detectable levels in saliva while N-terminal propeptide of type I collagen and alkaline phosphatase were close or below the detection limit. Serum levels of bone turnover markers were significantly higher than saliva levels. Correlation analysis revealed a strong correlation of serum osteocalcin and, to a lesser extent, also serum CTX values with bone mineral density in lumbar spine, femoral neck, or total hip, respectively. There was, however, no significant correlation of bone mineral density with the respective bone turnover markers in saliva. There was a trend that saliva osteocalcin correlates with femoral neck ( p  = 0.16) or total hip ( p  = 0.06). There was also no association between serum and saliva bone turnover markers. This study reveals that saliva cannot replace the withdrawal of serum to evaluate bone metabolism.

Purpose To study how many women are misdiagnosed with polycystic ovary syndrome (PCOS) instead of functional hypothalamic amenorrhea (FHA), which is important to improve overall well‐being, long‐term health, and fertility issues. Methods The FHA prevalence in a cohort of 401 women previously diagnosed with PCOS (revised Rotterdam criteria) was estimated retrospectively based on experts and previous studies: luteinizing hormone (LH) <2 IU/mL, LH <5.36 IU/mL, sex hormone binding globulin (SHBG) >53.3 nmol/L, Testosterone <0.36 ng/mL, and the formula of Beitl et al. [(7.05*testosterone ng/mL) − (0.005*SHBG nmol/L) + (0.117*LH mIU/mL) − 2.463 < 0]. Results The highest rate of women with suspicion of FHA in patients referred for PCOS was found when the SHBG cut‐off of ≥53.3 nmol/L was used (36.9%), followed by the use of the LH cut‐off of <5.36 IU/mL (12.5%). The minimal suspected rate was achieved with the LH cut‐off <2.0 IU/mL (1.7%). Women who fulfilled the criteria for PCOS phenotype D (ovulatory dysfunction and polycystic ovarian morphology) revealed the maximum rate for suspected FHA (up to 47.6%). Conclusion It is still necessary to evaluate reliable markers for the differential diagnosis between PCOS and FHA to avoid incorrect treatment, which might lead to negative long‐term effects in women with undiagnosed FHA. In this unselected population of women referred to a center specialized in gynecologic endocrinology for suspicion of PCOS, a minimum rate of misdiagnosed FHA patients of about 2% was found. It is necessary to evaluate reliable markers for the differential diagnosis between PCOS and FHA to avoid incorrect treatment, which might lead to negative long‐term effects in women with undiagnosed FHA.

We aimed to assess the systemic and hepatic renin-angiotensin-system (RAS) fingerprint in advanced chronic liver disease (ACLD). This prospective study included 13 compensated (cACLD) and 12 decompensated ACLD (dACLD) patients undergoing hepatic venous pressure gradient (HVPG) measurement. Plasma components (all patients) and liver-local enzymes (n = 5) of the RAS were analyzed using liquid chromatography–tandem mass spectrometry. Patients with dACLD had significantly higher angiotensin (Ang) I, Ang II and aldosterone plasma levels. Ang 1–7, a major mediator of the alternative RAS, was almost exclusively detectable in dACLD (n = 12/13; vs. n = 1/13 in cACLD). Also, dACLD patients had higher Ang 1–5 (33.5 pmol/L versus cACLD: 6.6 pmol/L, p < 0.001) and numerically higher Ang III and Ang IV levels. Ang 1–7 correlated with HVPG (ρ = 0.655; p < 0.001), von Willebrand Factor (ρ = 0.681; p < 0.001), MELD (ρ = 0.593; p = 0.002) and interleukin-6 (ρ = 0.418; p = 0.047). Considerable activity of ACE, chymase, ACE2, and neprilysin was detectable in all liver biopsies, with highest chymase and ACE2 activity in cACLD patients. While liver-local classical and alternative RAS activity was already observed in cACLD, systemic activation of alternative RAS components occurred only in dACLD. Increased Ang 1–7 was linked to severe liver disease, portal hypertension, endothelial dysfunction and inflammation.

Background To evaluate in women with functional hypothalamic amenorrhea (FHA), whether there is a difference between patients with and without polycystic ovarian morphology (PCOM) concerning the response to a gonadotropin releasing hormone (GnRH) stimulation test and to pulsatile GnRH treatment. Methods In a retrospective observational study, 64 women with FHA who underwent a GnRH stimulation test and 32 age-matched controls without PCOM were included. Pulsatile GnRH treatment was provided to 31 FHA patients and three-month follow-up data were available for 19 of these. Results Serum levels of gonadotropins and estradiol were lower in FHA women than in controls ( p  < 0.05). FHA patients revealed PCOM in 27/64 cases (42.2%). FHA patients without PCOM revealed lower anti-Müllerian hormone (AMH) levels than controls (median 2.03 ng/mL, IQR 1.40–2.50, versus 3.08 ng/mL, IQR 2.24–4.10, respectively, p  < 0.001). Comparing FHA patients with and without PCOM, the latter revealed lower AMH levels, a lower median LH increase after the GnRH stimulation test (240.0%, IQR 186.4–370.0, versus 604.9%, IQR 360.0–1122.0; p  < 0.001) as well as, contrary to patients with PCOM, a significant increase in AMH after three months of successful pulsatile GnRH treatment (median 1.69 ng/mL at baseline versus 2.02 ng/mL after three months of treatment; p  = 0.002). Conclusions In women with FHA without PCOM, the phenomenon of low AMH levels seems to be based on relative gonadotropin deficiency rather than diminished ovarian reserve. AMH tended to rise after three months of pulsatile GnRH treatment. The differences found between patients with and without PCOM suggest the former the existence of some PCOS-specific systemic and/or intra-ovarian abnormalities.

PurposeIt is still not clear whether to screen women with primary premature ovarian insufficiency for autoimmunity. Moreover, a possible association of autoimmunity with decreased bone mass density in premature ovarian insufficiency patients has not been evaluated. Thus, the objectives of this study were to review our experience with the use of an autoimmune screening panel in premature ovarian insufficiency women and to focus on bone mass density.MethodsIn a retrospective cohort study, 76 chromosomally normal women with primary premature ovarian insufficiency were included. The main outcome parameters were the results of an autoimmune screening panel and of dual-energy X-ray absorptiometry.ResultsMedian age was 33 years. Sixty percent of premature ovarian insufficiency patients revealed abnormal dual-energy X-ray absorptiometry results (minimal T-score < −1.0). Any signs of autoimmunity were found in 21 women (36.2%). The most frequent abnormal results were increased thyroperoxidase antibodies (24.1%) and thyroglobulin antibodies (20.7%). A longer duration of amenorrhea (β = −0.015; p = 0.007), any abnormality during autoimmune screening (β = −0.940; p = 0.010), and a lower body mass index (β = −0.057; p = 0.036) were associated with a lower minimal T-score.ConclusionIn chromosomally normal women with primary premature ovarian insufficiency, the prevalence of autoimmunity and decreased bone mass density seem high. Our data highlight the association between autoimmune abnormalities and decreased dual-energy X-ray absorptiometry results.

Vascular calcification is a component of cardiovascular disease, which is leading cause of death in patients with chronic kidney disease (CKD). A functional assay (T50-test) measuring the propensity of human serum to calcify associates with mortality and cardiovascular events in CKD patients. Calcification propensity is known to increase with CKD stage. We investigated whether the T50 readout is directly dependent on excretory kidney function (eGFR) or rather explained by deranged parameters of bone and mineral metabolism in the course of CKD. T50, along with markers implicated in calcification and mineral metabolism, were measured in a cross-sectional cohort of 118 patients with CKD stage 1–5. Associations of T50 with measured parameters were analysed and partial correlations performed to test to which extent the association of T50 with eGFR can be attributed to variation of these parameters. T50 correlates with eGFR, but serum levels of phosphate and calcium largely explain this association. Phosphate, magnesium, fetuin A, albumin, bicarbonate, and serum cross-laps but not Parathyroid Hormone or Fibroblast Growth Factor 23 are associated with T50 in multivariate adjusted models. These findings indicate that T50 values depend mainly on the concentration of promoters and inhibitors of calcification in serum, but not excretory kidney function.

Background and Objectives: Polycystic ovary syndrome (PCOS) is associated with an elevated risk of impaired mental health and psychiatric disorders, such as depression and anxiety. Physical factors like weight and hirsutism, as well as psychological factors, such as self-esteem and coping strategies, are all known to have an influence on mental health status. Aim: To assess psychological symptoms in women with and without PCOS, by use of the well-established, validated self-report questionnaire: Symptom Checklist-90-Revised (SCL-90); to determine the reliability of the SCL-90 for assessment of PCOS patients. Design: Prospective case-control study. Methods: Psychological symptoms were assessed using the German version of the SCL-90 in 31 PCOS women and 31 healthy controls. To test the impact of various parameters on numerical outcome parameters, correlation analyses were conducted. Results: PCOS women revealed significantly increased SCL-90 scores in seven out of the nine subscales (hostility subscale, anxiety subscale, depression subscale, paranoid ideation subscale, psychoticism subscale, somatization subscale, interpersonal sensitivity subscale, obsessive compulsive subscale), as well as in all three global indices (p < 0.05). SCL-90 scores were significantly positively correlated with perceived total stress and perceived helplessness and significantly negatively correlated with perceived self-efficacy (p < 0.05). Conclusions: PCOS women experienced higher levels of psychological symptoms including depressive and anxiety symptoms. Higher perceived stress, higher perceived helplessness and lower self-efficacy were associated with more psychological symptoms. Hence, there is a need to support PCOS women with their emotional regulation and coping strategies.

Background/Objectives: Gender-affirming hormone therapy (GAHT) is known to influence the lipid profiles of trans men and transmasculine individuals. Recent data show that moderate prolactin (PRL) elevations might exert beneficial metabolic effects (“HomeoFIT-PRL model”). The aim of this study is to investigate changes in PRL levels and possible associations between PRL and lipid profiles in this population after a year of GAHT. Methods: In a retrospective cohort study, 97 participants, who received GAHT with testosterone, were included. Blood lipids, PRL, and sex steroid hormone levels were evaluated prior to and at 10–14 months after treatment started. Results: The difference in PRL levels between baseline and follow-up was significant (p = 0.007) with a median difference of +2.3 ng/mL. Concerning blood lipids, the decline in high-density lipoprotein cholesterol (HDL-C) reached statistical significance (median 56 mg/dL versus 50 mg/dL; p < 0.001), and low-density lipoprotein cholesterol (LDL-C) and triglyceride levels increased (p = 0.023 and p = 0.045, respectively). Individuals with a PRL > 25 ng/mL at follow-up (n = 20, 20.6%) revealed increases in total cholesterol and LDL-C significantly less often. Overall, participants frequently displayed unfavorable changes in their lipid profile after 10–14 months of GAHT, as well as a slight but significant increase in PRL. About 20% of patients showed mild-to-moderate hyperprolactinemia (PRL > 25 ng/mL). However, such changes were associated with potentially beneficial dynamics in the lipid profile, at least for triglycerides. Conclusions: These findings seem in line with the HomeoFIT-PRL model suggesting that moderate elevations in PRL levels might exert beneficial metabolic effects. Increases in PRL after testosterone were common.