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Bone mineral density (BMD) expressed as the Z score of lumbar spine (L2-L4) and femoral neck in persistent young amenorrheic women () and normal menstruating women in dialysis ().
Source publication
Chronic renal failure in women is frequently associated with endocrine disturbances leading to menstrual disorders. However, most studies on renal osteodystrophy have not taken into account the possible role of these hormonal disturbances on the pathogenesis of bone alterations seen in these patients. In the present study, we evaluated bone mineral...
Context in source publication
Context 1
... biochemical parameters are shown in Table 2. As shown in Figure 2, there was a significant correlation between total serum estradiol and the Z score of lumbar spine BMD in the amenorrheic women (r 0.45, P 0.01). A similar positive correlation was obtained between total serum estradiol and absolute BMD values expressed as g/cm 2 (r 0.51, P 0.01). ...
Citations
... We adjusted keywords and conducted backward and forward snowballing searches and found 3 extra articles. Finally, a total of 22 articles [1,10,19,21,[26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43] were included in this meta-analysis. A PRISMA 2020 flowchart was provided to illustrate the screening and including process (Fig. 1). ...
... Of the included 22 articles from 13 countries (STable 2), 17 articles [10, 19, 26-35, 38, 40, 42, 43] compared hormone profiles of HD women to age-matched healthy controls (Ct) and 7 articles [1,26,27,31,38,39,41] compared hormone features of HD women to women after RT. What's more, 7 articles [1,21,29,30,36,37,43] provided hormones data of age-matched premenopausal HD women with or without regular menses (HDre vs. HDir). As a means to reduce heterogeneity among the studies, we created a subgroup consisting of studies where blood samples were obtained during the follicular phase of the menstrual cycle. ...
... Eight studies [1,26,27,29,30,34,35,43] took the blood samples of menstruating women during the follicular phase. Other 14 studies took blood samples of all subjects at the same time of a random day [19,32,33,41] or before HD [28,31] or others [21,36,42] or not mentioned [10,[37][38][39][40]. There were 12 articles [1, 10, 19, 21, 28-30, 33, 36, 37, 42, 43] excluding the medicine interfering for hormones assessment, which was one of the major factors for confounding assessment. ...
Background
A meta-analysis followed by PRISMA 2020 statement was performed aiming to present a whole prolactin and sex hormone profile in hemodialysis women.
Methods
Literatures were searched in PubMed, Cochrane library, Embase, and Web of science before March 11, 2023. Trial sequential analysis (TSA) was performed to test the conclusiveness of this meta-analysis. Egger’s test and trim-and-fill analysis was used to test publication bias. We took standardized mean difference (SMD) as pool effect of hormones values including prolactin (PRL), follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2) and progesterone (P). This study was registered in PROSPERO and the number was CRD42023394503.
Results
Twenty-two articles from 13 countries were analyzed. Combining the results of TSA and meta-analysis, we found that compared with healthy control, hemodialysis women had higher PRL, follicular FSH and LH values and lower P levels (PRL: I² = 87%, SMD 1.24, 95% CI: 0.79–1.69, p < 0.00001; FSH: I² = 0%, SMD 0.34, 95% CI: 0.13–0.55, p = 0.002; LH: I² = 39%, SMD 0.64, 95% CI: 0.34–0.93, p < 0.00001; P: I² = 30%, SMD − 1.62, 95% CI: -2.04 to -1.20, p < 0.00001). What’s more, compared with women after renal transplantation, hemodialysis women had higher PRL levels (I² = 0%, SMD 0.51, 95% CI: 0.25–0.78, p = 0.0001). There was not enough evidence to draw a conclusion on the comparison of hormones between regular and irregular menses hemodialysis women. Egger’s test and trim-and-fill analysis didn’t show significant publication bias.
Conclusions
Hemodialysis women had higher serum PRL, follicular phase FSH, LH and lower serum P values compared with healthy control. PRL values of hemodialysis women were also higher than that of women after renal transplantation.
... В работе J. Weisinger et al. (2000) выполнено сравнение костного и минерального метаболизма и состояния гипофизарно-гонадной оси в двух группах молодых диализных женщин: с персистирующей аменореей и регулярным менструальным циклом. В группе пациенток с аменореей значения трабекулярной МПК в поясничном отделе позвоночника были достоверно ниже и коррелировали с уровнем эстрадиола, а уровни фолликулостимулирующего гормона и биохимических маркеров костной резорбции были достоверно выше. ...
... В группе пациенток с аменореей значения трабекулярной МПК в поясничном отделе позвоночника были достоверно ниже и коррелировали с уровнем эстрадиола, а уровни фолликулостимулирующего гормона и биохимических маркеров костной резорбции были достоверно выше. Полученные результаты позволили сделать вывод, что аменорея у молодых диализных пациенток ассоциирована с более низкой МПК и усиленной резорбцией кости при сравнении с диализными пациентками с регулярным менструальным циклом [43]. ...
The article presents current data on mineral and bone disorders in patients with various stages of chronic kidney disease. The key points of bone lesions pathology are reflected, which include impaired secretion of parathyroid hormone and phosphorus-calcium metabolism, specific osteopathy and extraskeletal calcification, the relationship between bone pathology and cardiovascular complications is indicated. The role of diagnostic tools (FRAX questionnaire, bone densitometry, biochemical parameters and new biological markers) is discussed, approaches to the interpretation of research results are defined. Both general population and specific risk factors for bone strength decrease and occurrence of osteoporotic fractures pathology in chronic kidney disease are described.
... As in the general population [1], demographic factors such as older age, Caucasian ethnicity, and female gender predispose to increased fracture risk in CKD [3]. Late menarche [11] and menstrual disturbances [12] are also associated with low BMD in women with ESKD, indicating a role of hypogonadism similar to what is known in post-menopausal osteoporosis. ...
... Consistent with our understanding of the physiology of sex hormones, higher serum estradiol levels are associated with greater BMD in both pre- [12] and post-menopausal [31] women on dialysis. Further, younger women with persistent amenorrhea have lower BMD than those with normal menstrual cycles [12]. ...
... Consistent with our understanding of the physiology of sex hormones, higher serum estradiol levels are associated with greater BMD in both pre- [12] and post-menopausal [31] women on dialysis. Further, younger women with persistent amenorrhea have lower BMD than those with normal menstrual cycles [12]. Both higher testosterone [32,33] and estradiol [32,34] levels are associated with greater BMD in men with late-stage CKD. ...
Osteoporosis is a state of bone fragility with reduced skeletal resistance to trauma, and consequently increased risk of fracture. A wide range of conditions, including traditional risk factors, lifestyle choices, diseases and their treatments may contribute to bone fragility. It is therefore not surprising that the multi-morbid patient with chronic kidney disease (CKD) is at a particularly high risk. CKD is associated with reduced bone quantity, as well as impaired bone quality. Bone fragility in CKD is a composite of primary osteoporosis, accumulation of traditional and uremia-related risk factors, assaults brought on by systemic disease, and detrimental effects of drugs. Some risk factors are modifiable and represent potential targets for intervention. This review provides an overview of the heterogeneity of bone fragility in CKD.
... In a young cohort of women receiving haemodialysis (mean age = 36.5 ± 9.1 years) identified to have persistent amenorrhea (n = 31), oestradiol levels were significantly lower compared to women receiving dialysis with regular menstrual cycles (98.25 ± 24.1 vs. 315 ± 41.8 pg/ml, p < 0.001) [71]. In these women, Z-scores for LS aBMD by DXA was significantly lower (− 1.14 ± 1.2 versus 0.12 ± 0.81, p < 0.006) compared with those with regular menstrual cycles. ...
... Similarly, in pre-menopausal women with CKD, it would be more prudent to compare women who are amenorrhoeic (and assumed hypogonadal) versus those with regular menstrual cycles rather than using linear models assessed by a single hormone value (that are within the eugondal range) with bone outcomes. One observational study included in this systematic review examined pre-menopausal women with amenorrhea and found them to have lower LS aBMD compared those with regular menstrual cycles [71]. The interventional study by Matuszkiewicz-Rowinska et al. also assessed pre-menopausal women with amenorrhea and demonstrated a benefit of oestradiol/NE on LS and FN BMD following 12 months of treatment compared with placebo, indicating a potential role for HRT in preserving BMD in these women. ...
Purpose of Review
Patients with chronic kidney disease (CKD) have a greatly increased fracture risk compared with the general population. Gonadal hormones have an important influence on bone mineral density (BMD) and fracture risk, and hormone therapies can significantly improve these outcomes. Gonadal dysfunction is a frequent finding in patients with CKD; yet, little is known about the impact of gonadal hormones in the pathogenesis and treatment of bone health in patients with CKD. This systematic review and meta-analysis aimed to examine the effects of gonadal hormones and hormone therapies on bone outcomes in men and women with CKD.
Methods
EMBASE, MEDLINE, SCOPUS, and clinical trial registries were systematically searched from inception to February 14, 2018 for studies that assessed gonadal hormones or hormone treatments with bone outcomes in patients with CKD stage 3–5D. Two independent reviewers screened the titles and abstracts of search results according to inclusion criteria and assessed study quality and risk of bias using validated assessment tools.
Recent Findings
Thirteen studies met the inclusion criteria. Six moderate-to-high quality observational studies showed inconsistent association between any gonadal hormone and bone outcomes, limited by significant study heterogeneity. Five moderate-high risk of bias interventional studies examined treatment with selective oestrogen receptor modulators in post-menopausal women (four using raloxifene and one bazedoxifene) and demonstrated variable effects on BMD and fracture outcomes. Meta-analysis of raloxifene treatment in post-menopausal women demonstrated improvement in lumbar spine (SMD 3.30; 95% CI 3.21–3.38) and femoral neck (SMD 3.29; 95% CI 3.21–3.36) BMD compared with placebo. Transdermal oestradiol/norethisterone in pre-menopausal women receiving dialysis (n = 1 study), demonstrated BMD improvement over 12 months. Testosterone treatment for 6 months in dialysis-dependant men (n = 1 study) did not improve BMD.
Summary
There is evidence that raloxifene treatment may be beneficial in improving BMD in post-menopausal women with CKD. There is insufficient evidence for other hormone treatments in men or women. Despite high fracture rates and frequent gonadal dysfunction in patients with CKD, significant evidence gaps exist, and well-designed studies are required to specifically assess the impact of gonadal status in the pathogenesis of CKD-related bone fragility and its treatment.
... The effects of sex hormone levels on bone health in CKD has not been well described. Low levels of E are associated with reduced BMD in both men 7 and women 8,9 on hemodialysis, and BMD has been shown to improve with hormone replacement therapy in women. 10 In male patients, it has been suggested that the action of sex hormones on BMD could be mediated through the receptor activator of nuclear factorÀkB (RANK) and RANK ligand (RANKL) system, 11,12 although others have found no correlation between levels of T and BMD. ...
Introduction
Low levels of sex hormones are common in patients with chronic kidney disease (CKD) and may be a contributing factor to bone fragility. We investigated associations between levels of sex hormones and bone mineral density (BMD) in adult kidney transplantation candidates.
Methods
Volumetric BMD of spine and hip were measured by computed tomography. Parathyroid hormone (PTH), testosterone (T), estradiol (E), and sex hormone binding globulin were measured from fasting morning blood samples. Bioavailable (Bio) T and E were calculated based on constants for protein binding.
Results
A total of 146 patients (102 men and 44 women) were included in the analyses. The median age was 54 years (range, 32−72 years); 32% were diabetic; and 36% received maintenance dialysis therapy. In men, Bio T was positively associated with BMD at the lumbar spine (β = 5.02, P = 0.002), total hip (β = 6.35, P = 0.001), and femoral neck (β = 13.9, P = 0.002), independently of age, body mass index, dialysis, diabetes type 1 and 2, parathyroid hormone, and steroid exposure. Bio E was positively associated with BMD at the lumbar spine (β = 0.23, P = 0.03) and femoral neck (β = 0.61, P = 0.04) using the same fully adjusted model. In postmenopausal women, Bio T was positively correlated with lumbar spine BMD (r = 0.46, P = 0.02).
Conclusion
High endogenous levels of sex hormones were associated with greater bone density in male kidney transplantation candidates. Disturbances in the gonadal axis may contribute to skeletal fragility in men with late-stage CKD.
... Пациентки ГД с аменореей имеют значительно меньшую минеральную плотность поясничного отдела позвоночника по сравнению с пациентками ГД с сохранным МЦ. Сывороточные уровни фалликулостимулирующего гормона и маркеров костной резорбции были выше у пациенток ГД с аменореей [44]. ...
This article gives an overview of the scientific evidence on the impact of physical activity on various parameters of the health of people with end-stage renal disease. With examples of clinical observations, interrelations are established between nutritional status, menstrual disorders, osteopenia, erectile dysfunction and the impact on them of methods of physical rehabilitation.
... Пациентки ГД с аменореей имеют значительно меньшую минеральную плотность поясничного отдела позвоночника по сравнению с пациентками ГД с сохранным МЦ. Сывороточные уровни фалликулостимулирующего гормона и маркеров костной резорбции были выше у пациенток ГД с аменореей [44]. ...
This article gives an overview of the scientific evidence on the impact of physical activity on various parameters of the health of people with end-stage renal disease. With examples of clinical observations, interrelations are established between nutritional status, menstrual disorders, osteopenia, erectile dysfunction and the impact on them of methods of physical rehabilitation.
... Amenorrheic women on hemodialysis may also be at increased risk for metabolic bone disease [93]. In a recent study of 74 women on hemodialysis, trabecular bone mineral density was lower in amenorrheic patients when compared to those with regular menses. ...
... With regards to hormone replacement therapy, it has been noted that woman on hemodialysis are often not treated in the same manner as nonuremic women [94]. In three separate trials only 4.8, 6 and 11.3 % of post-menopausal females were noted to be receiving hormone replacement therapy [93][94][95], and this number is significantly reduced when compared to non-uremic women. Given the potential benefits of estrogen therapy on bone mineralization and cardiovascular morbidity, it is likely that such therapy is being underutilized in this patient population [96], and would warrant exploration. ...
Sexual dysfunction is a common finding in both men and women with chronic kidney failure. Common disturbances include erectile dysfunction in men, menstrual abnormalities in women, and decreased libido and fertility in both sexes. These abnormalities are primarily organic in nature and are related to uremia as well as the other comorbid conditions that frequently occur in the chronic kidney failure patient. Fatigue and psycho social factors related to the presence of a chronic disease are also contributory factors. Disturbances in the hypothalamic-pituitary-gonadal axis can be detected prior to the need for dialysis but continue to worsen once dialytic therapy is initiated. Impaired gonadal function is prominent in uremic men while the disturbances in the hypothalamic-pituitary axis are more subtle. By contrast, central disturbances are more prominent in uremic women. Therapy is initially directed towards optimizing the delivery of dialysis, correcting anemia with recombinant erythropoietin, and controlling the degree of secondary hyperparathyroidism with vitamin D. For many practicing nephrologists sildenafil has become the first line therapy in the treatment of impotence. In the hypogonadal man whose only complaint is decreased libido, testosterone may be of benefit. Regular gynecologic follow up is required in uremic women to guard against potential complications of unopposed estrogen effect. Uremic women should be advised against pregnancy while on dialysis. Successful transplantation is the most effective means of restoring normal sexual function in both men and women with chronic kidney failure.
... Sexual dysfunction is common in ESKD [76]. Amenorrheic young women with ESKD on dialysis have lower trabecular bone mineral density (BMD) and evidence of increased bone resorption when compared with regularly menstruating women on dialysis [77]. However, there are limited studies evaluating therapies, including hormone therapy, to treat hypogonadal signs and symptoms in the CKD population [78]. ...
Menstrual disorders, infertility and premature menopause are common but often underrecognized phenomena among women with chronic
kidney disease. Hypothalamic, rather than ovarian dysfunction, may be the cause of the abnormal reproductive milieu, which
can be at least partially reversed by kidney transplantation and increased intensity of hemodialysis. Endogenous sex hormones,
and specifically estradiol, appear to be renoprotective in women, although the effects of exogenous estradiol (as an oral
contraceptive and postmenopausal hormone therapy) on kidney function are more controversial. Treatment with postmenopausal
hormone therapy in women with end-stage kidney disease (ESKD) has been associated with improved quality of life, bone health
and markers of cardiovascular risk, as well as an increased risk of arteriovenous access thrombosis. The selective estrogen
receptor modulator raloxifene has been associated with both a decreased fracture risk as well as renoprotection in women with
kidney disease. Young women with ESKD are more likely to die from infection or develop malignancy, suggesting an immunomodulatory
role of estrogen. Whether the premature menopause commonly observed in female patients with kidney disease results in increased
cardiovascular morbidity and mortality is unknown, although preliminary studies have suggested a possible therapeutic role
for manipulation of the sex hormone milieu to mitigate risk in this population. Large, prospective, randomized studies examining
the role of sex hormones in women with kidney disease are required to address the question.
... Meanwhile, estrogen plays an important protective role in the kidneys of CKD patients [27][28][29][30]; thus, estrogen loss accelerates the progression of CKD. Therefore, estrogen deficiency might lead to more severe CKD-MBD, with increased bone resorption and decreased trabecular BMD [31,32]. It has been reported that estrogen administration can decrease the bone resorption rate and restore normal trabecular bone volume and trabecular connectivity in these CKD patients [33]. ...
... Barreto et al. [32] reported that amenorrheic female patients on hemodialysis presented with a lower BV/TV ratio than menstruating patients. Weisinger et al. [31] reported a significantly lower trabecular BMD in the lumbar spine of amenorrheic women compared with regularly menstruating dialysis patients. In this study, we found that serum BUN levels were higher in the CKD+OVX group than in the CKD group, indicating that estrogen deficiency aggravated CKD. ...
Background:
Chronic kidney disease (CKD) has been regarded as a grave public health problem. Estrogen is a critical factor for both renal protection and bone remodeling. Our previous study demonstrated that CKD impairs the healing of titanium implants. The aim of this study was to investigate the effects of estrogen deficiency on the mandibular bone in CKD mice.
Methods:
Forty eleven-week-old female C57BL mice were used in this study. Uremia and estrogen deficiency were induced by 5/6 nephrectomy and ovariectomy (OVX), respectively. After 8 weeks, the mice were sacrificed, and their mandibles were collected for micro-CT analysis and histological examination.
Results:
All the mice survived the experimental period. Serum measurements confirmed a significant increase in BUN in the CKD group that was further increased by OVX. OVX led to significant decreases in both the BV/TV and cortical thickness of the mandibular bone in CKD mice.
Conclusion:
In summary, our findings indicate that estrogen deficiency leads to further mandibular bone loss in CKD mice.
