Postmenopausal osteoporosis is a kind of degenerative disease, also described as "invisible killer." Estrogen is generally considered as the key hormone for women to maintain bone mineral content during their lives. Iron accumulation refers to a state of human serum ferritin that is higher than the normal value but less than 1000 μg/L. It has been found that iron accumulation and osteoporosis could occur simultaneously with the decrease in estrogen level after menopause. In recent years, many studies indicated that iron accumulation plays a vital role in postmenopausal osteoporosis, and a significant correlation has been found between iron accumulation and fragility fractures. In this review, we summarize and analyze the relevant literature including randomized controlled trials, systematic reviews, and meta-analyses between January 1996 and July 2022. We investigate the mechanism of the effect of iron accumulation on bone metabolism and discuss the relationship of iron accumulation, osteoporosis, and postmenopausal fragility fractures, as well as the main clinical treatment strategies. We conclude that it is necessary to pay attention to the phenomenon of iron accumulation in postmenopausal women with osteoporosis and explore the in-depth mechanism of abnormal bone metabolism caused by iron accumulation, in order to facilitate the discovery of effective therapeutic targets for postmenopausal osteoporosis.
Humans ; Female ; Osteoporotic Fractures ; Osteoporosis, Postmenopausal/drug therapy* ; Postmenopause ; Osteoporosis ; Bone Density ; Estrogens ; Iron/therapeutic use*

OBJECTIVES: Hysteroscopic adhesiolysis (HA) remains the mainstay on treatment for intrauterine adhesions (IUA). The fertility outcome of patients with moderate and severe intrauterine adhesions after HA is still far from satisfactory. Estrogen combined with progesterone is the most common treatment; however, they do not help in improving the fertility rate to the maximum because of the limitations. This retrospective, non-randomized controlled study will assess the effects of traditional Chinese medicine Yangmo decoction after HA in restoration of the endometrium and improvement of the fertility rate. METHODS: A total of 427 patients, who met the inclusion criteria, aged between 20 and 45 years and diagnosed with moderate or severe IUA underwent HA at the Third Xiangya Hospital from January to August 2021, were enrolled for this study. Participants were assigned into 2 groups: A Yangmo decoction group (n=213, patients were given Yangmo decoction consisting of Ginseng flower, Sanchi flower, Daidai flower, Snow lotus, Licorice and so on after HA), and an estrogen and progesterone group (n=214, patients were given estrogen and progesterone after HA). The following basic information was collected retrospectively for both groups, including age, parity, history of abortion, menstrual status, and times of hysteroscopic interventions. American Fertility Society (AFS) score was used by a senior surgeon and the density of opening of endometrial glands was evaluated during HA. The parameters were obtained from three-dimensional transvaginal ultrasound (3D-TVUS) preoperatively and postoperatively, to evaluate the efficacy of Yangmo decoction, estrogen, and progesterone. All patients were followed up on telephone to determine the fertility rate until 6 months from the last HA. RESULTS: Based on the basic information collected preoperatively, there were no significant differences between the groups (all P>0.05). Postoperatively, patients in the Yangmo decoction group had a better surgical success rate with a more significant AFS reduction (P<0.001), better density of opening of endometrial glands in the uterine cavity (P<0.000 1) after HA, and a better fertility rate (40.4%) in the time of 6 months after the last HA than those of the estrogen and progesterone group. CONCLUSIONS Yangmo decoction has better therapeutic efficacy in the treatment of intrauterine adhesion after HA than the combined effect of estrogen and progesterone. Yangmo decoction helps restore the endometrium and improve the fertility rate, therefore, it can be adopted as a routine practice for IUA patients who have fertility requirements.
Humans ; Young Adult ; Adult ; Middle Aged ; Retrospective Studies ; Progesterone/therapeutic use* ; East Asian People ; Medicine, Chinese Traditional ; Estrogens/therapeutic use*

With the process of urbanization and population aging in China, the burden of cardiovascular disease and the incidence of coronary heart disease among postmenopausal women have greatly increased. Studies have found that the incidence of coronary heart disease in postmenopausal women is closely related to the level of estrogen, but there are still difficulties of low efficiency and large side effects in current therapies. Kidney deficiency has a strong correlation with reproductive development and overall function. The clinical manifestations and characteristics of postmenopausal coronary heart disease patients conform to the pathogenesis of kidney deficiency in traditional Chinese medicine. The kidney-invigorating method has a good efficacy in treating postmenopausal coronary heart disease patients. This paper summarizes clinical and pharmacological evidences, expounds the relationship between kidney deficiency and the level of estrogen, and the pathological mechanism of the kidney-tonifying method in the treatment of coronary heart disease, and defines the clinical efficacy and advantages of the kidney-tonifying method. The method may become an effective method to prevent and treat postmenopausal coronary heart disease, and is expected to benefit patients with coronary heart disease better.
China ; Coronary Disease/drug therapy* ; Drugs, Chinese Herbal/therapeutic use* ; Estrogens ; Female ; Humans ; Kidney ; Medicine, Chinese Traditional

Aromatase is the rate-limiting enzyme in estrogen biosynthesis. The third generation aromatase inhibitors (AIs), represented by letrozoleand and anastrozole, can combine with aromatase, effectively reducing the estrogen level in the body. Because of its high efficiency, selectivity and reversibility, it has been used in the treatment of McCune-Albright syndrome, familial male-limited precocious puberty, gynecomastia, and adolescent boy with short stature. The good efficacy and safety of AIs have been observed. However, so far the drug instructions of AIs usually do not show indications for children; there are risks of adverse reactions involving liver and kidney function, lipid metabolism, hyperandrogenemia and bone metabolism; especially the long-term effects on reproductive system and bone metabolism are still not clear. Therefore, it is necessary to prescribe it carefully and follow up closely. It was not recommended that AIs be routinely used to improve adult height of adolescent boy with short stature. And more clinical evidences are needed for the safety and effectiveness of AIs prescribed in pediatrics.
Adolescent ; Aromatase Inhibitors ; therapeutic use ; Child ; Estrogens ; Humans ; Male ; Puberty, Precocious

BACKGROUNDMenopausal hormone therapy (MHT) has been proven to have beneficial effects on several components of metabolic syndrome. However, the effects vary according to different regimens, dosages, and duration of MHT. The aim of the study was to evaluate the effect of standard-dose 0.625 mg conjugated equine estrogen (CEE) and half-dose 0.3 mg CEE daily with different progestogens in a continuous sequential regimen on postmenopausal metabolic parameters in generally healthy postmenopausal women.

METHODSA prospective, open-label, randomized controlled clinical trial was conducted between February 2014 and December 2015. Totally 123 Chinese postmenopausal women with climacteric symptoms were included in this study and were randomly assigned to three groups: Group A received CEE 0.3 mg/micronized progesterone (MP) 100 mg daily; Group B received CEE 0.625 mg/MP 100 mg daily; and Group C received CEE 0.625 mg/dydrogesterone 10 mg daily. Drugs were given in a continuous sequential pattern. The duration of treatment was 12 months. Clinical, anthropometrical, and metabolic variables were measured. Data were analyzed according to intention-to-treat analysis, using Student's t-test and analysis of variance.

RESULTSA total of 107 participants completed the 12-month follow-up and were included in the data analysis. At 12 months of treatment, high-density lipoprotein cholesterol and apolipoprotein A significantly increased, and low-density lipoprotein cholesterol, fasting glucose, and glycosylated hemoglobin significantly decreased in Groups B and C, compared with baseline (all P < 0.05). Among the three groups, only Group C showed significantly increased triglycerides compared with baseline (1.61 ± 0.80 mmol/L vs. 1.21 ± 0.52 mmol/L, P = 0.026). Each group showed a neutral effect on total cholesterol, lipoprotein A, apolipoprotein B, and fasting insulin levels. No cardiovascular and venous thromboembolic events occurred in the three groups.

CONCLUSIONSAmong Chinese postmenopausal women, half-dose CEE was not sufficient to induce a favorable lipid and carbohydrate profile compared with standard-dose CEE. Adding natural MP may counterbalance the TG-increasing effect of CEE.

TRIAL REGISTRATIONClinicalTrials.gov, NCT01698164; https://clinicaltrials.gov/ct2/show/NCT01698164?term=NCT01698164&rank=1.

Apolipoproteins B ; blood ; Blood Pressure ; drug effects ; Body Composition ; drug effects ; Dydrogesterone ; administration & dosage ; therapeutic use ; Estrogens, Conjugated (USP) ; administration & dosage ; therapeutic use ; Female ; Humans ; Insulin ; blood ; Lipoprotein(a) ; blood ; Metabolic Syndrome ; blood ; drug therapy ; Middle Aged ; Postmenopause ; Progesterone ; administration & dosage ; therapeutic use ; Triglycerides ; blood

BACKGROUNDIt is now recognized that Cimicifuga foetida (C. foetida) extract is effective in alleviating menopausal symptoms. But the durations reported were usually short. The aim of this study was to investigate the effects of C. foetida extract therapy and different estrogen and progesterone sequential therapies, on the breasts of early postmenopausal women.

METHODSThis was a prospective randomized trial. Ninety-six early menopausal women were recruited and randomly assigned into three groups treated with different therapies for 2 years. Patients were given C. foetida extract in Group A, estradiol valerate and medroxyprogesterone acetate in Group B, and estradiol valerate and progesterone in Group C. Ultrasonography was used to monitor changes in breast during treatment.

RESULTSIn comparing breast glandular section thickness before and after 1 and 2 years of treatment, no significant difference was observed in Group A (11.97 ± 2.84 mm vs. 12.09 ± 2.58 mm and 12.61 ± 3.73 mm, P > 0.05); in Group B glandular section thickness had increased significantly (10.98 ± 2.34 mm vs. 11.84 ± 2.72 mm and 11.90 ± 3.33 mm, P < 0.05) after treatment, the same as Group C (11.56 ± 3.03 mm vs. 12.5 ± 3.57 mm and 12.22 ± 4.39 mm P < 0.05). In comparing breast duct width before and after 1 and 2 years of treatment, no significant difference was seen in Group A (1.07 ± 0.19 mm vs. 1.02 ± 0.18 mm and 0.98 ± 0.21 mm, P > 0.05); in Group B the duct width had a downward trend after treatment (0.99 ± 0.14 mm vs. 0.96 ± 0.22 mm and 0.90 ± 0.18 mm, P < 0.05), the same as Group C (1.07 ± 0.20 mm vs. 1.02 ± 0.17 mm and 0.91 ± 0.19 mm, P < 0.05). The nodules detected before treatment had disappeared after 1-year of treatment or exhibited no distinct changes in the three groups. However, new breast nodules had appeared after 2 years of treatment: There was one case in Group A, two cases in Group B and four cases in Group C, with breast hyperplasia after the molybdenum target check.

CONCLUSIONSIn early postmenopausal patients, C. foetida extract therapy and estrogen and progesterone therapy at low doses did not increase the incidence of malignant breast tumors.

Adult ; Breast ; drug effects ; Breast Neoplasms ; drug therapy ; Cimicifuga ; chemistry ; Estrogens ; therapeutic use ; Female ; Hormone Replacement Therapy ; Humans ; Male ; Middle Aged ; Plant Extracts ; pharmacology ; Postmenopause ; Progestins ; therapeutic use ; Software

BACKGROUNDThin endometrium is associated with poor reproductive outcomes; estrogen treatment can increase endometrial thickness (EMT). The aim of this retrospective cohort study was to investigate the factors influencing the effectiveness of estrogen treatment and reproductive outcomes after the treatment in patients with thin endometrium.

METHODSRelevant clinical data of 101 patients with thin endometrium who had undergone estrogen treatment were collected. Possible factors influencing the effectiveness of treatment were analyzed retrospectively by logistic regression analysis. Eighty-seven infertile women without thin endometrium who had undergone assisted reproduction served as controls. The cases and controls were matched for age, assisted reproduction method, and number of embryos transferred. Reproductive outcomes of study and control groups were compared using Student's t-test and the Chi-square test.

RESULTSAt the end of estrogen treatment, EMT was ≥8 mm in 93/101 patients (92.1%). Effectiveness of treatment was significantly associated with maximal pretreatment EMT (P = 0.017) and treatment duration (P = 0.004). The outcomes of assisted reproduction were similar in patients whose treatment was successful in increasing EMT to ≥8 mm and the control group. The rate of clinical pregnancy in patients was associated with the number of good-quality embryos transferred in both fresh (P = 0.005) and frozen-thawed (P = 0.000) embryo transfer cycles.

CONCLUSIONSThinner EMT before estrogen treatment requires longer treatment duration and predicts poorer treatment outcomes. The effectiveness of treatment depends on the duration of estrogen administration. Assisted reproductive outcomes of patients whose treatment is successful (i.e., achieves an EMT ≥8 mm) are similar to those of controls. The quality of embryos transferred is an important predictor of assisted reproductive outcomes in patients treated successfully with exogenous estrogen.

Endometrium ; drug effects ; Estrogens ; therapeutic use ; Female ; Humans ; Infertility, Female ; drug therapy ; therapy ; Male ; Pregnancy ; Pregnancy Rate ; Retrospective Studies

OBJECTIVETo evaluate the effects of estrogen on renal function of pregnant rabbits with hemorrhagic shock.

METHODSForty pregnant New Zealand white rabbits were randomized into 4 groups, namely normal control group (NG group, with anesthesia only), estrogen group (E2 group, with additional estrogen injection at 60 min), estrogen-hemorrhagic shock (E2SG) group and fructose-hemorrhagic shock (FSG) group. In the latter two groups, the rabbits were subjected to phlebotomy for 15 min to induce hemorrhagic shock with a blood pressure of 40 mmHg; after maintenance of the pressure for 45 min, intravenous injections of estrogen or fructose were given before resuscitation 20 min later. Blood urea nitrogen (BUN) and creatinine (Cr) concentration were measured at different time points and renal pathology of the rabbits was observed.

RESULTSNo significant differences were founding serum BUN and Cr levels between NG and E2G groups during the experiment. In FSG and E2SG groups, serum BUN level began to increase at 80 min after hemorrhagic shock and was significantly higher in FSG group (P<0.05); serum Cr level increased progressively from the start of the experiment and began to decrease at 60 min, with a faster rate of reduction in E2SG group (P<0.05).

CONCLUSIONEstrogen can effectively lower serum BUN and Cr levels and ameliorate renal pathologies to offer protective effect in pregnant rabbits against hemorrhagic shock.

Animals ; Blood Urea Nitrogen ; Estrogens ; pharmacology ; therapeutic use ; Female ; Kidney ; drug effects ; pathology ; Pregnancy ; Rabbits ; Shock, Hemorrhagic ; pathology ; physiopathology

OBJECTIVETo observe the effect of Modified Zuoguiwan (MZ) on the balance between helper T cell subsets 17 (Th17) and regulatory T cell subsets (Treg) in estrogen deficiency induced bone loss mice and to explore its mechanism.

METHODSTotally 50 BALB/c mice were divided into the sham-operation group, the ovariectomy model group, the low dose MZ group, the middle dose MZ group, and the high dose MZ group by random digit table, 10 in each group. Mice in the low, middle, and high dose MZ groups were respectively administered with MZ at the daily dose of 7.25, 14.50, and 29.00 g/kg by gastrogavage, 0.5 mL each time for 12 successive weeks. Meanwhile, mice in the sham-operation group and the ovariectomy model group were administered with equal volume by gastrogavage, 0.50 mL each time. The serum estradiol (E2) level was assessed by enzyme linked immunosorbent assay (ELISA). Bone mineral density (BMD) of thigh bone was measured with dual energy X ray absorptiometry. In addition, the population of Th17/Treg subsets in spleen mononuclear cells was analyzed by extracellular and intracellular staining method using flow cytometry. Moreover, the mRNA expression of IL-17A and TGF-β in the spleen mononuclear cells was detected by reverse transcription polymerase chain reaction (RT-PCR).

RESULTSCompared with the sham-operation group, both E2 and BMD significantly decreased, the percentage of Th17 subset and Th17/Treg ratio both increased, the percentage of Treg subset obviously decreased, the expression of IL-17A mRNA significantly increased, and the expression of TGF-β mRNA significantly decreased in the ovariectomy model group (all P < 0.05). Compared with the model group, BMD obviously increased, the percentage of Th17 subset and Th17/Treg ratio both decreased, the percentage of Treg subset obviously increased, the expression of IL-17A mRNA significantly decreased, and the expression of TGF-β mRNA significantly increased in the middle dose MZ group and the high dose MZ group (all P < 0. 05). Correlation analyses showed that BMD was positively related to both the serum E2 level and the percentage of Treg subset (P < 0.05), but negatively related to the percentage of Th17 subset (P < 0.05). In addition, the serum E2 level was positively related to the percentage of Treg subset, but obviously negatively related to that of Th17 subset (P < 0.05).

CONCLUSIONSThere was correlation between Th17/Treg imbalance and E2 deficient bone loss. MZ could decrease the proportion of Th17 subset, but elevate the proportion of Treg subset in E2 deficient bone loss mice. It could achieve therapeutic effect through adjusting the balance of Th17/Treg in E2 deficient bone loss mice.

Animals ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Estrogens ; deficiency ; metabolism ; Female ; Flow Cytometry ; Humans ; Interleukin-17 ; Mice ; Mice, Inbred BALB C ; Osteoporosis, Postmenopausal ; drug therapy ; RNA, Messenger ; Spleen ; T-Lymphocyte Subsets ; T-Lymphocytes, Helper-Inducer ; T-Lymphocytes, Regulatory ; Th17 Cells ; Transforming Growth Factor beta ; metabolism

OBJECTIVETo study whether effect of aspirin plus low-dose diethylstilbestrol is more effective and safer than high diethylstilbestrol dose alone on prevention of ovariectomy-induced osteopenia and dyslipidemia.

METHODSThirty-eight 4-month-old female SD rats were divided into baseline (BAS) group (n=6), sham operation group (n=8) and ovariectomy (OVX) group (n=24). The OVX group was further divided into vehicle treatment group (n=8), diethylstilbestrol (30 μg/kg•d) treatment group (OVX+D30 group, n=8), and aspirin (9 mg/kg•d) plus diethylstilbestrol (10 μg/kg•d) treatment group (OVX+A-D10 group, n=8). Their left tibiae were collected for the bone histomorphometric analysis in undecalcified sections. Left femurs were collected for the bone mineral density measurement.

RESULTSThe body weight and serum cholesterol were increased, while uterine weight and cancellous bone mass were decreased in OVX rats compared with the SHAM group. Cancellous bone mass was significantly increased, while body weight and bone resorption parameters were decreased in both A-D10 and D30 treatment group compared with OVX group. The rats treated with A-D10 showed significantly increased in bone formation parameters and decreased in serum triglyceride compared with the D30-treated rats.

CONCLUSIONAspirin plus low-dose diethylstilbestrol can effectively prevent osteopenia by reducing bone resorption, and is thus a better treatment modality for preventing dyslipidemia than high-dose diethylstilbestrol alone.

Animals ; Anti-Inflammatory Agents, Non-Steroidal ; pharmacology ; therapeutic use ; Aspirin ; pharmacology ; therapeutic use ; Biomarkers ; blood ; Body Weight ; drug effects ; Bone Density ; Bone Diseases, Metabolic ; blood ; prevention & control ; Bone and Bones ; drug effects ; Diethylstilbestrol ; pharmacology ; therapeutic use ; Drug Evaluation, Preclinical ; Drug Therapy, Combination ; Dyslipidemias ; blood ; prevention & control ; Estrogens, Non-Steroidal ; pharmacology ; therapeutic use ; Female ; Organ Size ; drug effects ; Ovariectomy ; Rats ; Uterus ; drug effects