Polycystic ovary syndrome (PCOS) is a common disease caused by complex endocrine and metabolic abnormalities in women of childbearing age. Metformin is the most widely used oral hypoglycemic drug in clinic. In recent years, metformin has been used in the treatment of PCOS, but its mechanism is not clear. In this study, we aimed to investigate the effect of metformin on PCOS and its mechanism through PCOS mouse model. Female C57BL/6J mice aged 4-5 weeks were intragastrically given letrozole (1 mg/kg daily) combined with a high-fat diet (HFD) for 21 days to establish the PCOS model. After modeling, metformin (200 mg/kg daily) was intragastrically administered. One month later, the body weight and oral glucose tolerance test (OGTT) were measured. Hematoxylin eosin (H&E) staining was used to detect the pathological changes of ovary. The serum levels of anti-Mullerian hormone (AMH), follicle-stimulating hormone (FSH), luteinizing hormone (LH), E₂ and testosterone (T) were measured by ELISA. The expression of DDX4/MVH was detected by immunohistochemistry. DDX4/MVH and PCNA were co-labeled by immunofluorescence. The protein levels of DDX4/MVH, PCNA, cyclin D2, AMPK and mTOR were detected by Western blot. The results showed that after metformin treatment, the body weights of PCOS mice were gradually returned to normal, glucose tolerance was significantly improved, serum E₂ levels were increased, while AMH, LH, T levels and LH/FSH ratio were decreased. Ovarian polycystic lesions were reduced with reduced atresia follicles. Furthermore, the number of proliferative female germline stem cells (FGSCs) and levels of proliferation related proteins (PCNA, cyclin D2) were significantly increased, and the p-mTOR and p-AMPK levels were markedly up-regulated. These results suggest that metformin treatment not only improves hyperandrogenemia, glucose intolerance and polycystic ovarian lesions in PCOS, but also activates the function of FGSCs. The underlying mechanism may be related to the phosphorylation of AMPK and mTOR. These findings provide new evidence to use metformin in the treatment of PCOS and follicular development disorder.
AMP-Activated Protein Kinases ; Animals ; Cyclin D2 ; Female ; Follicle Stimulating Hormone/therapeutic use* ; Humans ; Luteinizing Hormone/therapeutic use* ; Metformin/pharmacology* ; Mice ; Mice, Inbred C57BL ; Oogonial Stem Cells/metabolism* ; Ovarian Cysts/drug therapy* ; Ovarian Neoplasms ; Polycystic Ovary Syndrome/drug therapy* ; Proliferating Cell Nuclear Antigen/therapeutic use* ; TOR Serine-Threonine Kinases

Nonobstructive azoospermia (NOA) refers to the failure of spermatogenesis, which affects approximately 1% of the male population and contributes to 10% of male infertility. NOA has an underlying basis of endocrine imbalances since proper human spermatogenesis relies on complex regulation and cooperation of multiple hormones. A better understanding of subtle hormonal disturbances in NOA would help design and improve hormone therapies with reduced risk in human fertility clinics. The purpose of this review is to summarize the research on the endocrinological aspects of NOA, especially the hormones involved in hypothalamic-pituitary-testis axis (HPTA), including gonadotropin-releasing hormone, follicle-stimulating hormone, luteinizing hormone, prolactin, testosterone, estradiol, sex hormone binding globulin, inhibin B, anti-Müllerian hormone, and leptin. For the NOA men associated with primary testicular failure, the quality of currently available evidence has not been sufficient enough to recommend any general hormone optimization therapy. Some other NOA patients, especially those with hypogonadotropic hypogonadism, could be treated with hormonal replacement. Although these approaches have succeeded in resuming the fertility in many NOA patients, the prudent strategies should be applied in individuals according to specific NOA etiology by balancing fertility benefits and potential risks. This review also discusses how NOA can be induced by immunization against hormones.
Azoospermia/etiology* ; Follicle Stimulating Hormone ; Humans ; Luteinizing Hormone ; Male ; Sperm Retrieval ; Testis ; Testosterone/therapeutic use*

OBJECTIVE: To investigate the efficacy and safety of aromatase inhibitor letrozole in treatment of male children with disorders of sex development (DSD). METHODS: Clinical data of 12 male DSD children with a mean age of 14.6±2.5 years admitted to Peking Union Medical College Hospital from January 2014 to January 2016 were retrospectively analyzed. The patients were treated with letrozole (1.25-2.5 mg, once a day) for 3 months or longer, and followed up for 0.5-2.5 years. Clinical manifestation and laboratory test findings were documented, and the efficacy and safety were evaluated. RESULTS: After half-year treatment, the blood luteinizing hormone (LH), follicle-stimulating hormone (FSH) and testosterone levels of patients increased (all < 0.05), and estrogen levels decreased from baseline ( < 0.05). After 1 year of treatment, the blood testosterone level was significantly higher ( < 0.05); the LH and FSH levels tended to increase and the estrogen level tended to decrease, but there was no significant statistical difference ( >0.05). Semen was routinely detected in 8 patients, and sperms were detected in semen of 3 patients with hypospadias. There were no significant changes in biochemical results after treatment, and no significant adverse event was observed during the treatment. CONCLUSIONS Letrozole can effectively increase testosterone levels in patients with disorders of sex development and promote spermatogenesis, it has no significant adverse effects in short-term administration.
Adolescent ; Child ; Disorders of Sex Development ; drug therapy ; Follicle Stimulating Hormone ; Humans ; Letrozole ; therapeutic use ; Luteinizing Hormone ; Male ; Retrospective Studies ; Testosterone

Gonadotropin therapy is commonly used to induce virilization and spermatogenesis in male isolated hypogonadotropic hypogonadism (IHH) patients. In clinical practice, 5.6%-15.0% of male IHH patients show poor responses to gonadotropin treatment; therefore, testosterone (T) supplementation can serve as an alternative therapy to normalize serum T levels and promote virilization. However, treatment with exogenous T impairs spermatogenesis and suppresses intratesticular T levels. This retrospective study aimed to determine whether oral testosterone undecanoate (TU) supplementation together with human chorionic gonadotropin (hCG) would negatively affect spermatogenesis in IHH patients compared with hCG alone. One hundred and seven IHH patients were included in our study. Fifty-four patients received intramuscular hCG and oral TU, and 53 patients received intramuscular hCG alone. The median follow-up time was 29 (range: 12-72) months in both groups. Compared with the hCG group, the hCG/TU group required a shorter median time to normalize serum T levels (P < 0.001) and achieve Tanner stage (III and V) of pubic hair and genital development (P < 0.05). However, there were no significant differences in the rate of seminal spermatozoa appearance, sperm concentration, or median time to achieve different sperm concentration thresholds between the groups. In addition, there were no significant differences in side effects, such as acne and gynecomastia, observed in both groups. This study indicates that oral TU supplementation together with hCG does not impair spermatogenesis in treated IHH patients compared with hCG alone, and it shortens the time to normalize serum T levels and promote virilization.
Adolescent ; Adult ; Chorionic Gonadotropin/therapeutic use* ; Drug Therapy, Combination ; Follicle Stimulating Hormone/blood* ; Humans ; Hypogonadism/drug therapy* ; Luteinizing Hormone/blood* ; Male ; Retrospective Studies ; Spermatogenesis/drug effects* ; Testosterone/therapeutic use* ; Treatment Outcome ; Young Adult

Hypogonadotropic hypogonadism (HH) is a rare disease in which medical treatment has a high success rate to achieve fertility. This study aimed to analyze the efficacy of hormone replacement therapy and determine predictive factors for successful spermatogenesis and spontaneous pregnancy in patients with idiopathic HH. A total of 112 patients with low testosterone (T), luteinizing hormone (LH) and follicle-stimulating hormone (FSH), and normal prolactin levels were diagnosed with HH and administered LH and FSH analogs as hormone replacement therapy. During treatment, 96 (85.7%) patients had sperm present in ejaculate samples. Among these patients, 72 were married and wanted a child. Of these 72 patients, 48 (66.7%) of couples had pregnancies from natural conception. After initiation of treatment, the mean time for the appearance of sperm in semen was 9.48 months. There were no significant differences between baseline FSH, T, and LH levels; however, older age, larger testicular size, and low rate of undescended testes were favorable factors for successful spermatogenesis. Larger testicular size and older age were also the main predictive factors for natural conception. We found that patients with undescended testes had a younger age, smaller testes, and lower T levels compared with patients exhibiting descended testes. The rate of sperm found in the ejaculate was not significantly decreased in patients with undescended compared with descended testis (73.7% vs 87.6%, P = 0.261). The medical approach for males with HH and azoospermia provides a successful treatment modality in regard to successful spermatogenesis and achievement of pregnancy.
Adolescent ; Adult ; Chorionic Gonadotropin/therapeutic use* ; Follicle Stimulating Hormone/therapeutic use* ; Gonadotropins/therapeutic use* ; Hormone Replacement Therapy/methods* ; Humans ; Hypogonadism/pathology* ; Luteinizing Hormone/therapeutic use* ; Male ; Middle Aged ; Retrospective Studies ; Spermatogenesis/drug effects* ; Young Adult

OBJECTIVETo observe the efficacy differences between acupuncture combined with medication and medication alone for infertility patients with polycystic ovary syndrome (PCOS).

METHODSAccording to random number table, a total of 60 infertility patients with PCOS were randomly assigned into an observation group and a control group, 30 cases in each one. The patients in the control group were treated with diane-35 from the 3rd day into menstruation, and one menstrual cycle was taken as a session of treatment. At the same time of using diane-35, the patients in the observation group were treated with acupuncture at Guanyuan (CV 4), Qihai (CV 6), Sanyinjiao (SP 6), Zusanli (ST 36), Zigong (EX-CA 1), Shenshu (BL 23), Pishu (BL 20), Weishu (BL 21) and Ganshu (BL 18) during non-menstruation period; the acupuncture was given once every two days, three treatments per week. The patients in both groups were treated for two sessions. The basic sex hormone and body mass index (BMI) were compared between the two groups before and after treatment. After ovulation induction treatment, the endometrial thickness, amount of mature follicle, ovulation rate, clinical pregnancy rate, occurrence rate of ovarian hyperstimulation syndrome (OHSS) and the number of early spontaneous abortion were compared between the two groups during ovulation.

RESULTSAfter treatment, the luteinizing hormone (LH), testosterone (T) and BMI reduced in the observation group (all <0.05), while only LH reduced in the control group (<0.05). The reducing of estradiol (E), T and BMI in the observation group was more significant than that in the control group (all <0.05). The ovulation rate was 93.3% (28/30) in the observation group, which was higher than 80.0% (24/30) in the control group (<0.05). The rate of clinical pregnancy was 43.3% (13/30) in the observation group, which was higher than 33.3% (10/30) in the control group (<0.05). The differences of endometrial thickness, amount of mature follicle, occurrence rate of OHSS and number of early spontaneous abortion were not significant between the two groups (all >0.05).

CONCLUSIONAcupuncture as adjunctive treatment could improve BMI, reduce the levels of LH, E and T, increase ovulation reaction and effectively shorten reproduction cycles in infertility patients with PCOS.

Acupuncture Therapy ; Body Mass Index ; Combined Modality Therapy ; Cyproterone Acetate ; therapeutic use ; Drug Combinations ; Estradiol ; blood ; Ethinyl Estradiol ; therapeutic use ; Female ; Humans ; Infertility, Female ; therapy ; Luteinizing Hormone ; blood ; Ovulation Induction ; Polycystic Ovary Syndrome ; therapy ; Pregnancy ; Pregnancy Rate ; Testosterone ; blood

OBJECTIVETo compare the clinical efficacy differences between acupuncture at back- points of five , Geshu (BL 17), Shenmen (HT 7) and regular medication for the treatment of menopausal insomnia.

METHODSA total of 128 female patients of menopausal insomnia were randomly divided into an observation group and a control group, 64 cases in each one. Four patients in the observation group and 2 patients in the control group dropped out during the treatment. The patients in the observation group were treated with acupuncture at Feishu (BL 13), Xinshu (BL 15), Pishu (BL 20), Ganshu (BL 18), Shenshu (BL 23), Geshu (BL 17) and Shenmen (HT 7), once a day, and there was an interval of 2 days between every 5 days of treatment. The patients in the control group were treated with oral administration of alprazolam (0.4 mg or 0.8 mg) before sleep. Three-week treatment was taken as one course, and totally three courses were given in the two groups. Pittsburgh sleep quality index (PSQI), levels of estradiol (E), follicle-stimulating hormone (FSH) and luteinizing hormone (LH) were observed before treatment and 30 days after treatment; the efficacy was evaluated 30 days after treatment.

RESULTSEach item score and total score of PSQI 30 days after treatment were lower than those before treatment in the two groups (all <0.05), the scores in the observation group were lower than those in the control group (all <0.05). The levels of E 30 days after treatment were higher than those before treatment in the two groups (both <0.05), but the level of FSH and LH 30 days after treatment were lower than those before treatment in the two groups; the level in the observation group was superior to that in the control group (all <0.05). The total effective rate was 98.3% (59/60) in the observation group, which was better than 95.2% (59/62) in the control group (<0.05).

CONCLUSIONAcupuncture at Feishu (BL 13), Xinshu (BL 15), Ganshu (BL 18), Pishu (BL 20), Shenshu (BL 23), Geshu (BL 17), and Shenmen (HT 7) has better efficacy for menopausal insomnia than alprazolam.

Acupuncture Points ; Acupuncture Therapy ; Alprazolam ; therapeutic use ; Estradiol ; blood ; Female ; Follicle Stimulating Hormone ; blood ; Humans ; Luteinizing Hormone ; blood ; Menopause ; Sleep Initiation and Maintenance Disorders ; therapy ; Treatment Outcome

Aged ; Aged, 80 and over ; Androgen Antagonists/pharmacology* ; Androgens/blood* ; Cohort Studies ; Gonadotropin-Releasing Hormone/antagonists & inhibitors* ; Hormones/blood* ; Humans ; Luteinizing Hormone/blood* ; Male ; Middle Aged ; Orchiectomy ; Prostatic Neoplasms/surgery* ; Toremifene/therapeutic use*

Pulsatile gonadotropin-releasing hormone (GnRH) may induce spermatogenesis in most patients with congenital hypogonadotropic hypogonadism (CHH) by stimulating gonadotropin production, while the predictors for a pituitary response to pulsatile GnRH therapy were rarely investigated. Therefore, the aim of our study is to investigate predictors of the pituitary response to pulsatile GnRH therapy. This retrospective cohort study included 82 CHH patients who received subcutaneous pulsatile GnRH therapy for at least 1 month. Patients were categorized into poor or normal luteinizing hormone (LH) response subgroups according to their LH level (LH <2 IU l^-1 or LH ≥2 IU l^-1) 1 month into pulsatile GnRH therapy. Gonadotropin and testosterone levels, testicular size, and sperm count were compared between the two subgroups before and after GnRH therapy. Among all patients, LH increased from 0.4 ± 0.5 IU l^-1 to 7.5 ± 4.4 IU l^-1 and follicle-stimulating hormone (FSH) increased from 1.1 ± 0.9 IU l^-1 to 8.8 ± 5.3 IU l^-1. A Cox regression analysis showed that basal testosterone level (β = 0.252, P = 0.029) and triptorelin-stimulated FSH_60min(β = 0.518, P = 0.01) were two favorable predictors for pituitary response to GnRH therapy. Nine patients (9/82, 11.0%) with low LH response to GnRH therapy were classified into the poor LH response subgroup. After pulsatile GnRH therapy, total serum testosterone level was 39 ± 28 ng dl^-1 versus 248 ± 158 ng dl^-1 (P = 0.001), and testicular size was 4.0 ± 3.1 ml versus 7.9 ± 4.5 ml (P = 0.005) in the poor and normal LH response subgroups, respectively. It is concluded that higher levels of triptorelin-stimulated FSH_60minand basal total serum testosterone are favorable predictors of pituitary LH response to GnRH therapy.
Adult ; Cohort Studies ; Follicle Stimulating Hormone/blood* ; Gonadotropin-Releasing Hormone/therapeutic use* ; Gonadotropins/blood* ; History, 16th Century ; Humans ; Hypogonadism/pathology* ; Luteinizing Hormone/blood* ; Male ; Pituitary Gland/pathology* ; Predictive Value of Tests ; Retrospective Studies ; Sperm Count ; Testis/pathology* ; Testosterone/blood* ; Treatment Outcome ; Triptorelin Pamoate/therapeutic use* ; Young Adult

BACKGROUNDPolycystic ovary syndrome (PCOS) is an endocrine disease that affects gynecological health. Treatment of PCOS remains a big challenge for clinicians.

OBJECTIVEThis meta-analysis was developed to compare the efficacy of co-treatment with traditional Chinese medicine (TCM) and letrozole against letrozole monotherapy in the treatment of PCOS.

SEARCH STRATEGYRandomized controlled trials (RCTs) were electronically retrieved from PubMed, Cochrane Library, China Biomedical Literature Database, China National Knowledge Infrastructure and Wanfang Data; related papers that were not available electronically were manually checked. All papers were assessed according to the Cochrane Handbook for Systematic Reviews of Interventions and the valid data were analyzed using Revman software (The Cochrane Collaboration, Copenhagen, Denmark).

INCLUSION CRITERIAWe included RCTs that compared co-treatment with TCM and letrozole against letrozole monotherapy in women with PCOS, which was defined by anovulation, biochemical or clinical hyperandrogenemia and polycystic ovaries. We included trials from all sources.

DATA EXTRACTION AND ANALYSISTwo independent reviewers extracted data, and evaluated study quality according to the Cochrane Handbook for Systematic Reviews of Interventions criteria for RCT, including issues of patient randomization, blinding and bias.

RESULTSEight RCTs, involving a total of 537 patients, were included in the present study. The meta-analysis showed that the cycle ovulation rate, the pregnancy rate and the total effective rate of symptom treatment were higher in treatments combining TCM with letrozole, compared with letrozole monotherapy. Although the rate of luteinizing hormone (LH)/follicle-stimulating hormone (FSH) and the body mass index of the group receiving combined therapy were lower than in letrozole monotherapy, no statistical difference was found in the LH and FSH level between the two groups.

CONCLUSIONAvailable evidence showed that co-treatment with TCM and letrozole was more effective than letrozole monotherapy in the treatment of PCOS.

Female ; Follicle Stimulating Hormone ; blood ; Humans ; Luteinizing Hormone ; blood ; Medicine, Chinese Traditional ; Nitriles ; therapeutic use ; Polycystic Ovary Syndrome ; blood ; therapy ; Publication Bias ; Randomized Controlled Trials as Topic ; Triazoles ; therapeutic use