Preserved testicular artery at varicocele repair

Whether or not varicocele causes infertility is a contentiously debated issue. This study aimed to compare semen parameters and pregnancy rate in infertile males who underwent varicocelectomy with preserved or accidentally ligated testicular artery. Ninety-five infertile oligoasthenozoospermic patients with left-sided varicocele were subjected to subinguinal varicocelectomy with trial of preserving testicular artery. According to absence or presence of testicular artery in the histological excised pedicle the cases were divided into two groups; group 1 ( n  = 60) with preserved testicular artery and group 2 ( n  = 35) where the artery was accidentally ligated being not defined or injured. Semen analysis was carried out after 4, 8 and 12 months and post-operative pregnancy rate was assessed after 1 year. Serum follicle-stimulating hormone (FSH), luteinising hormone (LH) and total testosterone (T) were estimated pre- and post-operatively. Semen parameters (total sperm count, sperm concentration and sperm motility) showed significant increase post-operatively compared with pre-operative parameters but were comparable in both groups with no significant difference. Serum FSH, LH, T hormones and pregnancy rate (23.3% versus 22.9%) 1 year post-operatively showed no significant difference. It is concluded that accidental ligation of testicular artery has no deleterious effect on semen parameters during primary varicocele repair if the testicular arterial supply was not compromised.     

Melatonin hormone profile in infertile males

Melatonin is a hormone produced by the pineal gland. There is much controversy about its relationship to the male reproductive process. In this study, seminal plasma as well as the serum melatonin levels were studied in different infertile male groups and were correlated with their semen parameters and hormonal levels. One hundred twenty male cases subdivided into six equal groups were consecutively included; fertile normozoospermic men, oligoasthenozoospermia (OA), OA with leucocytospermia, OA with varicocele, non-obstructive azoospermia (NOA) with high serum follicle stimulating hormone (FSH) and NOA with normal FSH. Semen analysis, estimation of melatonin, FSH, testosterone (T) and prolactin (PRL) hormone was carried out. Mean level of serum melatonin was higher than its corresponding seminal concentrations in all investigated groups with a positive correlation between their levels (r = 0.532, p = 0.01). Serum and seminal plasma melatonin levels in all infertile groups were reduced significantly compared with their levels in the fertile group. The lowest concentrations were in OA with leucocytospermia group. Melatonin in both serum and semen demonstrated significant correlation with sperm motility (r = 607, 0.623 respectively, p = 0.01). Serum melatonin correlated positively with serum PRL (r = 0.611, p = 0.01). It may be concluded that melatonin may be involved in the modulation of reproductive neuroendocrine axis in male infertility. Also, low levels of melatonin in semen were observed in infertile groups having reduced sperm motility, leucocytospermia, varicocele and NOA.     

Bromocriptine for infertile males with mild hyperprolactinemia: hormonal and spermatogenic effects

To clarify the influence of hyperprolactinemia on spermatogenesis and steroidogenesis in infertile male patients, the serum prolactin (PRL), luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone, and estradiol concentrations were and the effect of bromocriptine treatment on spermatogenesis was examined. A total of 1234 patients were evaluated and 147 men had hyperprolactinemia. Of these, only 30 had PRL concentrations more than twice the upper limit of normal and most of them had a little excess over the upper limit. For 10 of these 30, serum hormone concentrations were measured and semen was analyzed before and after bromocriptine administration. No relationship between the PRL and other hormone concentrations was found. No changes were noted in the LH, FSH, testosterone, or estradiol concentrations, or in the sperm density and motility after treatment. The mean PRL decreased from 26.5 +/- 4.5 to 1.4 +/- 1.8 ng/mL. In infertile men who are mildly hyperprolactinemic, bromocriptine administration does not improve semen analysis, although it does normalize the PRL.     

Evidence for a stimulatory role of high doses of recombinant human follicle‐stimulating hormone in the treatment of male‐factor infertility

The efficacy of recombinant human follicle‐stimulating hormone (rhFSH) in the treatment of normogonadotropic patients with male‐factor infertility was assessed. Forty‐five infertile men with moderate/severe oligoasthenozoospermia and normal FSH, luteinizing hormone (LH) and testosterone (T) levels were treated with high rhFSH dose (300 IU) on alternate days for ≥4 months. In all, the seminal parameters, endocrine profile (FSH, LH, prolactin (PRL), total and free T and estradiol) and pregnancy rate were evaluated before, during and after rhFSH treatment. Fifteen infertile men were treated with placebo and studied in the same way, as control group. rhFSH treatment induced a marked increase in sperm count and no change in sperm motility, morphology and viability. No changes in seminal parameters were observed in the placebo group. FSH levels increased during treatment with rhFSH and not with placebo. No variations in LH, PRL, free and total T and estradiol were evidenced during treatment. A significant pregnancy rate in rhFSH versus placebo patients was also highlighted. Prolonged treatment with high rhFSH doses leads to increase sperm count and improve the spontaneous pregnancy rate in normogonadotropic infertile patients with oligoasthenozoospermia. rhFSH may represent a rational and useful tool in the treatment of male‐factor infertility.     

Body mass index,waist‐to‐hip ratio,waist circumference and waist‐to‐height ratio cannot predict male semen quality: a report of 1231 subfertile Chinese men

There were controversial results between obesity‐associated markers and semen quality. In this study, we investigated the correlations between age, obesity‐associated markers including body mass index (BMI), waist‐to‐hip ratio (WHR), waist‐to‐height ratio (WHtR) and waist circumference (WC), the combination of age and obesity‐associated markers, semen parameters and serum reproductive hormone levels in 1231 subfertile men. The results showed that BMI, WC, WHR and WHtR were positively related to age, and there were also positive relations between BMI, WHR, WC and WHtR and between sperm concentration (SC), total sperm count (TSC), progressive motility (PR), sperm motility and per cent of normal sperm morphology (NSM). However, age, each of obesity‐associated markers and the combination of obesity‐associated markers and age were unrelated to any of semen parameters including total normal‐progressively motile sperm count (TNPMS). Age, BMI, WHR, WC and WHtR were negatively related to serum testosterone and SHBG levels. However, only serum LH and FSH levels were negatively related to sperm concentration, NSM and sperm motility. In a conclusion, although age and obesity have significant impacts on reproductive hormones such as testosterone, SHBG and oestradiol, semen parameters related to FSH and LH could not be influenced, indicating that obesity‐associated markers could not predict male semen quality.     

Relationships between serum hormone levels and semen quality among men from an infertility clinic

Participation rates in epidemiologic studies on semen quality are generally very low, raising concerns as to the potential for selection bias. Since hormones both initiate and maintain spermatogenesis, they may serve as surrogates of semen quality in epidemiologic studies. For this reason, in the present study, we explored the influence and predictive ability of reproductive and thyroid hormones on semen quality among men who were partners in an infertile couple. Between 1999 and 2003, 388 men were recruited from Massachusetts General Hospital Andrology Laboratory for clinical evaluation of fertility status. Fresh semen samples were assessed for quality (concentration, motility and morphology) and the serum levels of hormones, including follicle-stimulating hormone (FSH), luteinizing hormone (LH), inhibin B, sex hormone-binding globulin (SHBG), testosterone, free androgen index, free T4, total T3, and thyroid-stimulating hormone (TSH), were measured. Multiple logistic regression revealed increased odds for below-reference sperm concentration and morphology in men with increased FSH, and decreased odds for below-reference sperm concentration and motility in men with increased inhibin B. When FSH and inhibin B were divided into quintiles, the relationships with sperm concentration showed evidence of a threshold value. However, the ability of specific FSH (10 IU/L) and/or inhibin B (80 pg/mL) cutoff values to predict semen quality was lower than in previous reports. In multiple linear regression analysis, FSH and LH were inversely associated with sperm concentration, motility, and morphology. Inhibin B and free T4 were positively associated with sperm concentration, while there was a suggestive positive association between testosterone and sperm motility. In conclusion, we have found that FSH, LH, inhibin B, testosterone and free T4 levels are associated with human semen parameters. Additional consideration should be given to the utility of serum hormone levels as a surrogate for semen quality in epidemiologic studies in which the collection of semen is difficult due to logistical and/or volunteer rate constraints.     

Evaluation of serum level of Osteocalcin hormone in male infertility

The suggested concept of “bone as an endocrine organ” had shed the light on the role of osteocalcin, an osteoblast secreted hormone, in regulation of testosterone production. This study aimed to assess the association between the active undercarboxylated form of osteocalcin (ucOC) and semen parameters and hormonal levels in infertile male patients. The study was carried on 34 infertile male patients and 20 fertile healthy control males. Semen analysis and serum level of testosterone, LH and FSH were performed in addition to serum level of ucOC in cases and controls. The results revealed significant differences between cases and controls in all measured semen and hormonal parameters. In addition, significant higher level of ucOC in cases than control group (p = .019). On the other hand, ucOC was not related significantly to any of the measured hormones or semen parameters. There was no significant correlation between ucOC and sperm concentration, total motility, morphology (p = .594, .640, .940 respectively) and similarly between ucOC and testosterone level or LH level (p = .275, .954 respectively). The significant higher level of ucOC in infertile cases cannot be used as a predictor of male reproductive parameters.     

生殖激素检测在男性不育症诊断中的意义

本文报道了我院对３１５例男性不育症患者在第一次就诊时进行血清生殖激素ＦＳＨ、ＬＨ、Ｔ、ＰＲＬ、Ｅ２水平的检测，并进行详细的病史询问、常规体检和精液分析等检查。结果显示血清Ｔ值在不同的精子密度层次的男性不育症患者均呈正态分布。睾丸容积减少，ＦＳＨ、ＬＨ上升，Ｔ／ＬＨ下降，提示睾丸功能损害，并且Ｔ／ＬＨ的比值更能反映间质细胞的功能。血清ＰＲＬ和Ｅ２值在诊断高催乳素血症不育有意义，但在男性生育者和不生育者之间无明显差别。而且ＦＳＨ值在鉴别睾丸原发性与梗阻性无精子症是一项重要指标。作者讨论了血清生殖激素测定在不育症诊断中、在判定睾丸功能的损害程度中的意义。     

Anogenital distance and reproductive parameters in young men

The purpose of this study was to assess the relationship between anogenital distance (AGD) measures and semen quality and serum reproductive hormone levels in Caucasian young men from southern Spain. Two variants of AGD [from the anus to the posterior base of the scrotum (AGD_AS) and to the cephalad insertion of the penis (AGD_AP)] were assessed in 215 university students. Semen parameters (semen volume, sperm concentration, total sperm counts, motility and morphology) and serum reproductive hormones (follicle stimulating hormone, luteinising hormone, inhibin B, testosterone, calculated free testosterone, oestradiol and sex hormone‐binding globulin) were also determined. Associations between AGD measures and the semen quality and reproductive hormone levels were tested using multiple regression analyses. Overall, median sperm concentration was 44.0 × 10⁶ ml^?1 (5th–95th percentiles: 8.9–129 × 10⁶ ml^?1), median total sperm count was 121 × 10⁶ (18.0–400 × 10⁶), and mean (SD) testosterone level was 21.7 nmol/l (6.9). Mean (SD) AGD_AS and AGD_AP measures were 48.3 mm (11.6) and 128 mm (12.0) respectively. In the multivariable analysis, AGD measures were not associated with any semen parameters or any of the reproductive hormone levels, which is in contrast to results of studies of US young men or infertile men. Further research is warranted to confirm these findings.     

Effect of psychological stress on fertility hormones and seminal quality in male partners of infertile couples

The present study evaluated the effect of psychological stress on male fertility hormones and seminal quality in male partner of infertile couples. Seventy male partners of infertile couples were evaluated for level of psychological stress using Hospital Anxiety and Depression Score (HADS) questionnaire, serum total testosterone, luteinising hormone (LH) and follicle‐stimulating hormone (FSH) by electrochemiluminescence assay and serum GnRH by ELISA. Seminal analysis was performed as per WHO guideline. Nineteen (27%) of them had HADS anxiety and depression score ≥8 (abnormal HADS score). The persons having abnormal HADS had lower serum total testosterone, higher serum FSH and LH than those of persons having normal HADS. Serum total testosterone correlated negatively with HADS, but LH and FSH correlated positively. There was no change in GnRH with the change in stress or testosterone levels. Sperm count, motility and morphologically normal spermatozoa were lower in persons having abnormal HADS. Sperm count correlated positively with total testosterone and negatively with FSH and LH. Abnormal sperm motility and morphology were related to lower testosterone and higher LH and FSH levels. Psychological stress primarily lowers serum total testosterone level with secondary rise in serum LH and FSH levels altering seminal quality. Stress management is warranted for male infertility cases.     

Hormone load tests in infertile male patients.

The recognition that discreet hormonal abnormalities may cause ovulation disorders in women suggested that the male partner of infertile women might also suffer from unrecognized hormonal dysfunction amendable to substitution therapy. We obtained a combined stimulation test with gonadotropin-releasing hormone (GnRH), thyreotropin-releasing hormone (TRH), and ACTH in 225 males with childless spouses, when the couple sought to have children for at least one year. The following hormone levels were determined: estradiol (E), thyroid-stimulating hormone (TSH), prolactin, testosterone (T), dihydrotestosterone (DHT), androstenedione(A), 17-OH-pregnenolone (17-OH-Preg), 17-OH-progesterone (17-OHP), dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEAS), cortisone (F), and 21-desoxycortisone (21DF). Basal and stimulated, and adrenal-testicular steroids with and without ACTH stimulation failed to demonstrate a relevant relationship to semen parameters. Gonadotropin levels had a significant negative correlation to all important semen parameters (testicular volume, sperm count, motility, morphology, and vitality) and were positively correlated to spermiogenetic defects. Stimulated LH values were more clearly associated with spermiogenetic defects than basal LH. Nonetheless, basal FSH concentrations were more informative than LH. Stimulated prolactin values were positively correlated with both gonadotropin and with sperm morphology. E concentrations had a significant positive correlation with both basal and poststimulation DHEAS values, and showed a highly negative correlation with sperm count, morphology, and vitality. In comparison, good sperm parameters were associated with high poststimulation T concentrations. The results of this study suggest that basal FSH and E concentrations, as well as the stimulated LH, T, and prolactin determinations, should be included in the evaluation of male sterility.     

不育男性抗苗勒管激素与生殖激素及精液质量参数关系的研究

目的探讨男性不育患者精浆和血清抗苗勒管激素(AMH)与血清生殖激素及精液参数之间关系。方法选取2018年9~12月于我院生殖中心就诊的男性不育患者107例,按照《世界卫生组织人类精液检查与处理实验室手册(第五版)》操作规范检测精液体积、精子浓度、前向运动精子(PR)百分比、精子顶体酶、精子DNA完整性、正常形态精子率,根据精液参数分为4组:少精子症组(n=15)、弱精子症组(n=26)、少弱精子组(n=31)、正常精子组(n=35),比较各组患者精浆和血清AMH及血清FSH、LH、催乳素(PRL)、T、E 2之间的差异,并对精浆和血清AMH与生殖激素及精液参数的相关性进行统计分析。结果弱精子症组血清AMH水平高于其他3组,但各组间差异无统计学意义(P>0.05);正常精子组精浆AMH水平[中位数(四分位距)]为1.28(7.71)ng/ml,显著高于少精子症组[0.11(1.26)ng/ml]和少弱精子组[0.16(2.15)ng/ml](P<0.05)。相关性分析显示,血清AMH与生殖激素及精液参数不存在相关(P>0.05);精浆AMH与血清FSH、LH呈负相关(P<0.05),与血清T呈正相关(P<0.05);精浆AMH与精子总数、精子浓度、PR%呈正相关(P<0.05),与其他精液参数不相关(P>0.05)。结论不育男性精浆AMH与血清生殖激素及精子浓度、活力具有一定的相关性,一定程度上反映睾丸生精功能,对男性不育的诊断和治疗有一定的参考作用。     

Predictive factors associated with successful varicocele repair a study of 139 infertile men with valicocele

PURPOSE: To determine pretreatment parameters which predict improvements following varicocele repaire in semen quality. MATERIALS AND METHODS: We retrospectively evaluated a total of 139 infertile patients who underwent varicocelectomy from February 1995 to March 2000. A logistic regression analysis was performed to identify parameters associated with improvements in semen quality. Parameters evaluated included varicocele grade, age, testicular volume, serum testosterone, liteinizing hormone (LH), follicle-stimulating hormone (FSH), preoperative sperm density and sperm motility. RESULTS: Of 139 patients 71 (51.0%) improved sperm concentration and 59 (42.4%) improved sperm motility postoperatively. Overall, median sperm density significantly increased from 10 x 10(6)/ml preoperatively to 30 x 10(6)/ml postoperatively. Sperm motility also significantly increased 33% to 45%. In logistic regression analysis, varicocele grade (odds ratio [OR] = 5.7; 95% confidential interval [CI : 1.9-17), FSH level ([OR] = 0.76; [CI]: 0.60-0.96) and sperm motility ([OR] = 1.03; [CI]: 1.0-1.1) were independent predictive factors for improvement in sperm concentration. CONCLUSION: Varicocelectomy improves sperm concentration and motility. Our data suggest that patients with grade 3 varicocele, low serum FSH level and high sperm motility are more likely to benefit from varicocele repair in sperm concentration.     

Clinical evaluation of spermatogenic activity of processed Shilajit in oligospermia

The safety and spermatogenic activity of processed Shilajit (PS) were evaluated in oligospermic patients. Initially, 60 infertile male patients were assessed and those having total sperm counts below 20 million ml⁻¹ semen were considered oligospermic and enrolled in the study ( n  = 35). PS capsule (100 mg) was administered twice daily after major meals for 90 days. Total semenogram and serum testosterone, luteinising hormone and follicle-stimulating hormone were estimated before and at the end of the treatment. Malondialdehyde (MDA), a marker for oxidative stress, content of semen and biochemical parameters for safety were also evaluated. Twenty-eight patients who completed the treatment showed significant ( P  < 0.001) improvement in spermia (+37.6%), total sperm count (+61.4%), motility (12.4–17.4% after different time intervals), normal sperm count (+18.9%) with concomitant decrease in pus and epithelial cell count compared with baseline value. Significant decrease of semen MDA content (−18.7%) was observed. Moreover, serum testosterone (+23.5%; P  < 0.001) and FSH (+9.4%; P  < 0.05) levels significantly increased. HPLC chromatogram revealed inclusion of PS constituents in semen. Unaltered hepatic and renal profiles of patients indicated that PS was safe at the given dose. The present findings provide further evidence of the spermatogenic nature of Shilajit, as attributed in Ayurvedic medicine, particularly when administered as PS.     

Seminal fibronectin in fertile and infertile males

This study aimed to assess seminal plasma fibronectin in fertile and infertile males. Ninety infertile males were investigated; asthenozoospermia (n = 27), asthenoteratozoospermia (n = 30), oligoasthenoteratozoospermia (n = 33) compared with 20 healthy fertile controls. They were subjected to semen analysis, seminal plasma fibronectin estimation by radial immune diffusion, serum testosterone (T) and follicle stimulating hormone (FSH) estimation by ELISA. There was significant increase of seminal plasma fibronectin among different infertile groups compared with the controls. Significant negative correlation was elicited between seminal fibronectin and sperm count, sperm motility grades A, B, A + B, sperm velocity, linear velocity, linearity index, sperm normal forms and serum T. Seminal fibronectin showed significant positive correlation with grade D sperm motility and serum FSH. ROC curve analysis discriminating controls and other infertile groups demonstrated criteria value of < 674 mg l(-1) (sensitivity 100% and specificity 96.4%). It is concluded that increased seminal fibronectin is associated with decreased sperm count and sperm motility.     

它莫西芬对促性腺激素、睾酮及精液参数影响的研究

本文报告它莫西芬治疗特发性少精症对卵泡刺激素_(ESH)、黄体生成素_(LH)、睾酮(T)以及对精子数量、活力、精浆果糖等参数的影响。采用的双盲法对39例受试者分为实验组、实验对照组、安慰组。结果表明服用它莫西芬20mg/日3个月,可以明显增加血中FSH、LH、T水平,对精子活力,精浆果糖浓度无明显影响。对精子密度在3个月服药期间个体差异较大,均数无明显增加。从临床角度而言,它莫西治疗特发性少精症不育可能对配偶妊娠是有益的。     

Body mass index has no impact on sperm quality but on reproductive hormones levels

The influence of overweight and obesity on sperm quality and reproductive hormone levels is under discussion. The aim of the present retrospective study was to evaluate the influence of body mass index (BMI) on sperm quality and reproductive hormones. We analysed semen samples and serum levels of FSH, LH, T and PRL of a total of 2110 men attending our andrology unit from 1994 to 2010 due to infertility work‐up. Patients were stratified according to their BMI in four groups. Main outcome measures were sperm motility, morphology and concentration. Serum levels of FSH, LH, T and PRL were evaluated as well. No statistically significant difference was found for sperm quality and BMI between patients categorised according to the four BMI levels. T (P < 0.001) and LH (P = 0.006) significantly differed between the four groups. In multivariable analysis, BMI did not have significantly independent influence on all assessed sperm quality parameters, whereas BMI significantly influenced hormone values for LH (P = 0.001), T (P = <0.001) and PRL (P = 0.044). We therefore conclude that BMI has no significant impact on sperm quality parameters. However, serum levels of LH, T and PRL were significantly influenced by BMI.     

Gonadotropins,testosterone and prolactin in men with abnormal semen findings and an evaluation of the hormone profile

Over a 4-year period, 259 men were investigated regarding primary (86.5%) or secondary (13.5%) infertility. Men with azoospermia had significantly higher concentrations of FSH and LH and lower concentrations of testosterone than those with spermatozoa. High concentrations of FSH and LH in serum were found in case of low sperm density. Men with low testicular voluem had high concentrations of FSH and LH and low concentrations of testosterone. FSH was closely correlated with LH and also with total testicular volume. A negative correlation was found between both gonadotropins and testosterone. The correlation between LH and testosterone was stronger in azoospermic men than in those with spermatozoa in semen. Serum concentrations of prolactin were higher in men with high sperm motility than among men with low motility of spermatozoa. Otherwise, prolactin concentrations were not correlated either with sperm density or with the morphology of spermatozoa or total testicular volume. A ‘hormone profile’ of FSH, LH and testosterone concentrations is suggested useful in the routine investigation of the infertile man, as more information is given by this profile than by FSH concentrations alone.     

精浆和血清生殖激素与精液质量的关系

目的为了评估精液质量不同的男性精浆和血清生殖激素的浓度与精子浓度及活动力的关系,探索精浆与血清生殖激素的关系。方法对301名男性进行精液检查,按照精液的质量参数将受试对象分成4组:精液正常组(n=176),弱精子症组(n=66),少精子症组(n=40)和非梗阻性无精子症组(n=19)。采用电化学发光免疫法测定各组受试对象血清卵泡刺激素(FSH)、黄体生成素(LH)、泌乳素(PRL)、孕酮(P)、睾酮(T)和雌二醇(E2)六项生殖激素和精浆PRL、T、P和E2四项生殖激素的浓度,比较组间差异并进行相关性分析。结果精液正常组和弱精子症组血清FSH和E2的浓度显著低于少精子症组和非梗阻性无精子症组(P0.05),精液正常组血清LH和P的浓度显著低于弱精子症、少精子症和非梗阻性无精子症的人群(P0.05);而精液正常、弱精子症和少精子症三组精浆PRL的浓度则高于非梗阻性无精子症组(P0.05)。除了非梗阻性无精子症组,受试者血清FSH的浓度与其精子浓度呈负相关(r分别为-0.350、-0.273和-0.448,P0.05)。精液正常组精浆PRL的浓度和精子的浓度之间呈正相关(r=0.269,P0.05);在少精子症组中,亦有相同趋势的相关性(r=0.432,P0.05)。结论精浆PRL及血清FSH的浓度能够反映精子浓度或活动力,在男性不育的病因分析中具有一定的指导价值。     

Lepidium meyenii （ Maca ） improved semen parameters in adult men

Aim: The present study was designed to determine the effect of a 4-month oral treatment with tablets of Lepidium meyenii (Maca) on seminal analysis in nine adult normal men aged 24 - 44 years old. Methods: Nine men received tablets of Maca (1500 or 3000 mg/day) for 4 months. Seminal analysis was performed according to guidelines of the World Health Organization (WHO). Serum luteinizing hormone (LH), follicle stimulating hormone (FSH), prolactin (PRL), testosterone (T) and estradiol (E2) were measured before and after treatment. Results: Treatment with Maca resulted in increased seminal volume, sperm count per ejaculum, motile sperm count, and sperm motility. Serum hormone levels were not modified with Maca treamaent. Increase of sperm count was not related to dose of Maca. Conclusion: Maca improved sperm production and sperm motility by mechanisms not related to LH, FSH, PRL, T and E2.