Protective effect of loboob (a Persian traditional remedy) on sexual hormones, antioxidant activities and stereological changes of testis tissue on busulfan induced oligospermia in rats

Loboob as a traditional drug in Iranis known for its beneficial effects on busulfan-induced oligospermia. In this experimental study, protective effects of loboob (a Persian traditional remedy) on sexual hormones, antioxidant levels and stereological changes of testis tissue were evaluated in an oligospermia rat model induced by busulfan. Fifty male rats were randomly divided into five different groups: control, received no treatments; and the other groups administrated with a single dose of busulfan (10 mg/kg body weight). After 30 days, these groups were treated with 0, 35, 70 or 140 mg/kg/day of loboob for 60 days. Blood samples were collected for hormone and antioxidant enzyme assays. Unbiased stereology was performed on testis tissues to evaluate the volume of different parts of the testis and the number of various testis cells. Data indicated that FSH, LH and MDA were increased, and testosterone, catalase, SOD were decreased in the busulfan group, while treatment with loboob at 70 and 140 mg/kg significantly improved these parameters (P <0.05). Treatment with 70 and 140 mg/kg of loboob ameliorated the germinal epithelium volume, types A and B spermatogonia, spermatocytes, elongated and round spermatids, and Sertoli cells in the seminiferous tubules (P <0.05). High concentration of loboob also improved testis weight and volume, and leydig cell number (P <0.05). Thus, loboob is more effective for the recovery of seminiferous tubules and their cells than for the interstitial tissue. Loboob with various antioxidants, minerals and vitamins could overcome the side effects of busulfan.

Effect of herbicide based formulations on structure and function of testis in rats

For instant weed management, widely used herbicide formulations (HFs) are Paraquat based formulation (PBF) or Glyphosate based formulation (GBF). Here, we investigated the effect of PBF Gramoxone® and GBF Roundup® on the structure and function of the testis of the male Wistar rats at the pubertal or post pubertal stage. Male rats were gavaged with Gramoxone® (5 mg/kg body wt.) or Roundup® (250 mg/kg body wt.). The treatment period of 25 days starts on a postnatal day (PND) 28 to 53 (from pre-pubertal to the pubertal stage) or 60 days from PND 28 to 88 (from prepubertal to the post pubertal stage). Age-matched control animals received distilled water. The structure of the testes was evaluated by observing changes in its histology and the function of the testes was assessed by estimating serum follicle-stimulating hormone (FSH), luteinizing hormone (LH) and testosterone levels. No significant effect was observed in the structure and function of the testes of the pubertal stage rats on exposure to both herbicide formulations. However, shrunken and distorted seminiferous tubules with oligozoospermia in testes, a non-significant decrease in FSH and LH, and a significant reduction in testosterone levels were noted in the post pubertal stage rats. The results indicated that changes in the testes of post pubertal groups are due to a longer duration of exposure to the Gramoxone® or Roundup® than in pubertal groups, and also the effect of these two formulations was more on the testis structure and function than on the pituitary-testis axis

Relationship between menstrual disorder and ovarian morphology of adolescent women / 西安交通大学学报(医学版)

Objective To study the relationship between menstrual disorder and ovarian morphology of adolescent women in order to provide basis for diagnosis of adolescent polycystic ovary syndrome (PCOS).Methods We analyzed the clinical data of 212 patients with adolescent menstrual disorders 2 years after menstruation collected from the Department of Gynecology and Women's Health of First Affiliated Hospital of Xi'an Jiaotong University between September 2014 and September 2015.Results ① Oligomenorrhea was the most common in the 212 adolescent women (33.96 ％),followed by amenorrhea (16.51％).There was a significant difference in F-G score and acne score among patients with different types of menstrual disorder (F=1.39,1.77,all P＜0.05),the highest in those with oligomenorrhea.② The volume of the ovary,number of sinusoidal follicles,maximum area of the ovary in women with oligomenorrhea were significantly higher than those in non-oligomenorrhea women (t =2.89,5.76,6.23,all P＜ 0.05).③ Clinical manifestations differed significantly among normal ovarian group,MFO group and PCO group (x2=43.25,P＜0.05).Incidence rate of oligomenorrhea ranked the top in polycystic ovary group (49.30％),followed by multiple ovarian follicles group (42.59％),and there were significant differences in blood LH,T,and LH/FSH (F=3.45,2.43,2.76,all P＜0.05) was found in PCO group.There was significant difference in diagnosis of puberty PCOS (x2=26.58,P＜0.05).④ Among these 212 adolescent women,45 ones had puberty PCOS (21.23％).The ovary volume,number of sinus follicles,and the largest area in the obese patients were significantly higher than those in non-obese group (t =3.42,7.89,4.02,all P＜0.05);HOMA IR was also significantly higher than that in non-obese group (t =8.89,10.62,all P ＜ 0.05).Conclusion Oligomenorrhea is the most common menstrual disorder in adolescent women.Ovarian morphological abnormalities occur in most women with oligomenorrhea and obesity,who should be followed up regularly.

Contribution of luteinizing hormone to Alzheimer’s disease / 国际药学研究杂志

Luteinizing hormone(LH)is a gonadotropin of hypothalamic-pituitary-gonadal axis(HPG), secreted by the anterior pituitary. The secretion of LH is directly controlled by the release of gonadotropin releasing hormone(GnRH), acts at the ovaries and testes to stimulate the production of gonadal hormones. Aging leads to increases in LH, and higher serum levels of LH has been observed in Alzheimer’s disease(AD)patients when compared to age-matched controls. Evidences from basic research and epidemiological investigation support the critical role of elevated LH in pathogenic process of AD and deteriorating cognitive decline. Here we summarize the recent discoveries containing human AD epidemiological evidence for LH, cognitive impairments resulting from LH activity, LH in AD pathology and LH receptor signaling mechanisms.

Clinical Study on Electroacupuncture in Mitigating the Symptoms Related to Menopausal Transition / 上海针灸杂志

Objective To observe and compare the regulating effect between electroacupuncture and sham electroacupuncture on the symptoms of menopausal transition and levels of estradiol (E2), follicle-stimulating hormone (FSH), and luteinizing hormone (LH), for evaluating the clinical efficacy of electroacupuncture in mitigating the relevant symptoms of menopausal transition. Method Thirty eligible subjects with menopausal transition were randomized into a treatment group and a control group, 15 cases in each group. The treatment group was intervened by electroacupuncture at the ordinary acupoints, while the control group was by electroacupuncture at non-meridian points. The E2, FSH, and LH contents were detected after intervention and at the 20th week during the follow-up study, the flush score and Menopause Rating Scale (MRS) were evaluated respectively after 4-week and 8-week treatment and at the 20th week and 32nd week during the follow-up study, and the safety of electroacupuncture was also estimated.Result The flush and MRS scores were significantly changed after 4-week and 8-week treatment and at the 20th week and 32nd week during the follow-up study in both groups compared to that before the treatment in the same group (P<0.01,P<0.05). There was a significant difference in comparing the changes of MRS score after 8-week treatment between the two groups (P<0.01). There were significant differences in comparing the changes of flushing scores between the two groups after 8-week treatment and at the 20th week and 32nd week during the follow-up study (P<0.01). The serum levels of E2, FSH, and LH were significantly changed in the treatment group after 8-week treatment (P<0.05). There were significant differences in comparing the changes of FSH and LH levels between the two groups after 8-week treatment (P<0.05). The difference in comparing the change of serum E2 level between the two groups at the 20th week during the follow-up study was statistically significant (P<0.05). Conclusion Electroacupuncture can improve the flushing intensity and produce a benign regulation on the relevant hormone levels in menopausal transition, though this regulation is insignificant when the treatment terminates.

Contribution of luteinizing hormone to Alzheimer′s disease / 国际药学研究杂志

Luteinizing hormone(LH)is a gonadotropin of hypothalamic-pituitary-gonadal axis(HPG),secreted by the anteri?or pituitary. The secretion of LH is directly controlled by the release of gonadotropin releasing hormone(GnRH),acts at the ovaries and testes to stimulate the production of gonadal hormones. Aging leads to increases in LH,and higher serum levels of LH has been ob?served in Alzheimer′s disease(AD)patients when compared to age-matched controls. Evidences from basic research and epidemiologi?cal investigation support the critical role of elevated LH in pathogenic process of AD and deteriorating cognitive decline. Here we sum?marize the recent discoveries containing human AD epidemiological evidence for LH,cognitive impairments resulting from LH activi?ty,LH in AD pathology and LH receptor signaling mechanisms.

Dynamic study on levels of serum PRL, LH, FSH, E2 and development of ovarian follicles in different phases of estrus cycle in gerbils / 中国比较医学杂志

Objective To investigate the numbers of corpus luteum and ovarian follicles and compare the levels of serum prolactin (PRL), luteinizing hormone (LH), follicle-stimulating hormone (FSH) and estradiol (E2 ) in different phases of estrus cycle in female gerbils .Methods Consecutively taking vaginal smears of the gerbils and directly examined under light microscope to distinguish the four phases of the estrus cycle .Hematoxylin and eosin staining was used to histological examination of the gerbil ovaries , and to detect the levels of serum PRL , LH, FSH and E2 by ELISA assay during estrus cycle .Results The proportion of cornified vaginal exfolliated cells could be the basis to distinguish four phases respectively:proestrus, oestrus, metoestrus, and dioestrus.Moreover, there were no significant differences between the numbers of ovarian follicles in different phases of estrus cycle .The numbers of corpus luteum in preoestrus were significantly lower than that in the other phases of estrus cycle ( P <0.05 ) .The levels of serum PRL and LH were increasing constantly from preoestrus to dioestrus , and both reached a peak at dioestrus ( P<0.05 ) .The levels of serum FSH and E2 both peaked at preoestrus , and were significantly higher than those at oestrus , metoestrus and dioestrus ( P<0.05).Conclusions There are no significant differences between the numbers of ovarian follicles in different phases of estrus cycle .Gonadotropin , prolactin and estradiol paly important roles in the regulation of estrous cycle .The phases during which surges of FSH and E 2 occur in Mongolian gerbils are similar to those of rats and mice , while the PRL and LH are different .Our findings provide further reference to the study of reproductive physiology of Mongolian gerbils .

Effects of environmental lead pollution on blood lead and sex hormone levels among occupationally exposed group in an E-waste dismantling area / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To study the effects of environmental multi-media lead pollution on blood lead and sex hormone levels among lead exposed males engaged in E-waste dismantling, and the correlation between confounding factors and sex hormone levels.</p><p><b>METHODS</b>An E-waste dismantling area in Taizhou of Zhejiang Province was selected as the research site. One hundred and fifty two samples were collected from the groundwater, soil, rice, corn, chicken, and pork in the dismantling area. The effects of the multi-media lead pollution on the male blood lead and sex hormone levels of FSH, LH, and T, as well as the correlation with confounding factors, were studied.</p><p><b>RESULTS</b>The blood lead concentrations in the males aged under 31, from 31 to 45 and from 46 to 60 were 98.55, 100.23, and 101.45 μg/L, respectively. Of all the environmental media lead exposures, the groundwater, rice and soil were main contributing factors to the lead accumulation in humans. FSH and LH levels increased with the age while the T levels decreased with the age instead. There was a significant correlation between the FSH and LH levels and wearing masks.</p><p><b>CONCLUSION</b>There was correlation between the FSH, LH, and T levels, and the mean values of lead concentrations in environmental media, and the sex hormone levels were correlated with the confounding factor of wearing masks.</p>

Hormonas reprodcctivas de importancia veterinaria en hembras domésticas rumiantes / Reproductive hrmmones of veterinary importance in domestic ruminant females

En el presente trabajo se revisan las principales hormonas reproductivas en hembras domésticas rumiantes, considerando sus características e interacciones, además de los métodos de determinación y las concentraciones que se reportan de cada una de dichas hormonas, durante las diferentes fases del ciclo estral. El eje hipotálamo-pituitario-ovárico controla la actividad reproductiva, principalmente, a través de las interacciones entre la Hormona Folículo Estimulante (FSH), la Hormona Luteinizante (LH), el Estradiol (E2) y la Progesterona (P4). Durante la fase folicular, las gonadotropinas estimulan el desarrollo de los folículos, promoviendo la proliferación de las células de la granulosa por parte de la FSH; su pico está asociado al surgimiento de la onda folicular, después de la cual decrece la concentración plasmática de FSH, y da inicio a la desviación folicular. Esto permite al folículo dominante expresar receptores para la LH, además de producir inhibina y E2. El alto nivel circulante de E2 induce la liberación de la Hormona Liberadora de Gonadotropinas (GnRH) desde el hipotálamo, resultando en un pico de LH, de amplitud y frecuencia suficiente para estimular la maduración final del folículo y la posterior ovulación. Las altas concentraciones de E2 influyen también sobre la presentación de los cambios fisiológicos y comportamentales durante el estro. La fase luteal está caracterizada por el predominio de la P4, cuya concentración se relaciona con el desarrollo del cuerpo lúteo. Esta hormona es indispensable para el reconocimiento y mantenimiento de la preñez y sus perfiles pueden llegar a determinar si existe la predisposición de un animal a sufrir pérdidas embrionarias tempranas. Se considera que los incrementos o disminuciones en las concentraciones séricas de cada hormona marcan cambios en las fases del ciclo estral, y es fundamental conocer la actividad de dichas hormonas mediante la determinación de su concentración sanguínea normal para cada una de las etapas reproductivas.

The main reproductive hormones in domestic female ruminants are reviewed in this paper, including their characteristics, interactions and concentrations besides the determination methods and concentrations reported in each hormone during the different phases of the estrous cycle. The hypothalamus-pituitary-ovarian axis, controls reproductive activity, mainly, through interactions between the Follicle-stimulating Hormone (FSH), Luteinizing Hormone (LH), Progesterone (P4) and Estradiol (E2). During the follicular phase, gonadotropin hormones stimulate follicle development, promoting the proliferation of granulosa cells on the FSH side. The FSH peak is associated with the emergence of the follicular wave after which, its plasmatic concentration decreases and the follicular deviation begins. This allows the dominant follicle to express LH-receptors and to produce inhibine and E2. The high level of flowing E2 induces the release of Gonadotropin Releasing Hormone (GnRH) from the hypothalamus, resulting in a LH of enough amplitude and frequency to stimulate the final maturation of the follicle and the subsequent ovulation. High plasma concentrations of E2, also influence the appearance of physiological and behavioral changes during estrous. The luteal phase is characterized by the dominance of P4, whose concentration is related to the development of the luteal body. This hormone is essential for pregnancy and its profiles recognition and maintenance, and it can even determine if there exist predisposition of an animal to suffer early embrionary loss. It is considered that increase or decrease in plasma concentration of each hormone, determine changes in the estrous cycle phases and, it is fundamental to know the activity of such hormones, by determining their normal blood concentration for each of the reproductive stages.

Cambios en la sccreción de los esteroides ovários y de la hormona luteinizantee durante el ciclo estral en la oveja: una revisión / Changes in theseecretion of ovrian steroids and luteinizing hormone during thhe estrous cycle in the ewe: a review

Los machos y las hembras ovinas ubicadas en altas latitudes presentan variaciones estacionales en la actividad reproductiva. La actividad sexual de las ovejas es estimulada por la disminución del fotoperiodo, de suerte que los animales que muestran estacionalidad reproductiva pueden disminuir su respuesta al reducirse la latitud. El eje hipotalámico hipofisiario funcional es esencial para la reproducción en mamíferos. El hipotálamo secreta el decapéptido, hormona liberadora de gonadotropinas (GnRH), responsable de iniciar una cascada de eventos que regula las gónadas. Durante el ciclo estral de la oveja, los niveles circulantes de la hormona luteinizante (LH) y de la progesterona (P4) están inversamente relacionados, evidenciando que la P4 podría inhibir la secreción tónica de LH. La P4, de acuerdo con sus efectos, es el esteroide ovárico más importante en las hembras mamíferas y está implicada en la compleja regulación de la función reproductiva. Durante la fase luteal del ciclo estral, la P4, producida por el cuerpo lúteo, inhibe la secreción de la GnRH hipotalámica y, consecuentemente, disminuye la concentración periférica de las gonadotropinas. La fase folicular inicia con la disminución de las concentraciones de P4, ocurrida después de la luteólisis, y es caracterizada por el aumento en la secreción de las gonadotropinas y del estradiol (E2). Esta elevación en el E2 circulante provoca el surgimiento del pico preovulatorio de LH, causado por el abrupto y continuo incremento en la secreción de GnRH. Las mediciones seriadas de E2, P4 y LH al momento de la ovulación en la oveja han demostrado que la secreción máxima del estrógeno desde los folículos preovulatorios precede el surgimiento de la LH. Datos recientes han mostrado que otros esteroides secretados por el folículo preovulatorio pueden actuar sinérgicamente con el estradiol para inducir la ovulación. La presente revisión pretende abordar las relaciones temporales existentes entre la circulación de LH y la secreción de los esteroides ováricos, 17-β estradiol y progesterona, durante el ciclo estral de la oveja.

Ewes and rams from temperate latitudes show seasonal variations in reproductive activity. Sheep sexual activity is stimulated by alterations in the photoperiod, so that animals displaying reproductive seasonality can reduce their response to seasonality as latitude decreases. A functional hypothalamic pituitary axis is essential for mammalian reproduction, since the hypothalamus secretes the decapeptide, gonadotropin-releasing hormone (GnRH) that is responsible for initiating the cascade of events that regulate gonadal function. During the estrous cycle of the ewe, circulating LH and P4 levels are inversely related, thus providing circumstantial evidence that progesterone may inhibit tonic LH secretion. Progesterone (P4), in terms of the cumulative duration of its effects, is the most important ovarian steroid secreted during the lifetime of the female mammal and it’s central to the complex regulation of normal reproductive function. During the luteal phase of the estrous cycle, the P4 produced by the corpus luteum inhibits hypothalamic GnRH secretion, and consequently, peripheral gonadotrophin concentrations are low. The follicular phase, which is initiated by the decline in circulating P4 concentrations after luteolysis, is characterized by increased gonadotrophin and Estradiol (E2) secretion. This rise in circulating E2 induces the preovulatory LH surge, which is caused by a robust, abrupt, and continuous increase in GnRH secretion. Serial measurements of E2, P4 and LH during ovulation time in the ewe have shown that maximum secretion of estrogen from pre-ovulatory follicles precedes the LH surge. Recent data show that other steroids secreted by the pre-ovulatory follicle may act synergistically with oestradiol in inducing ovulation. The present review was undertaken to observe discuss the temporal relationship between circulating LH and the secretion of the ovarian steroids, estradiol 17-β and progesterone, during the oestrous cycle in the ewe.

The effect of Gengnianningxin capsule on serum FSH、LH、E_2 and symptomsin patients with female climacteric syndrome of fever due to yin-deficiency / 重庆医科大学学报

Objective:To observe the effect of Gengnianningxin capsule on serum follicle stimulating hormone (FSH),luteinizing hormone (LH),estradiol (E 2) and clinical symptoms in patients with female climacteric syndrome of fever due to yin-deficiency.Methods:105 cases of patients with female climacteric syndrome of fever due to yin-deficiency were randomly divided into treatment group(70 cases) and control group (35 cases).Treatment group was treated by Gengnianningxin capsule,and control group was treated by Gengnianan tablet for 30 days.Levels of serum FSH,LH and E 2 were determined,meanwhile variation of symptom scores of climacteric syndrome were observed.Results:Levels of serum E 2 in the treatment group was increased significantly and levels of serum LH decreased significantly after treatment ( P

Effects of D-galactose on lumber vertebra density and serum testosterone concentration in male rats / 中国临床药理学与治疗学

AIM: To observe the effects of D-galactose on the lumber vertebra body and investigate the reasons. METHODS: 12 rats at age of 6 months were divided into two groups, control group and D-galactose group (n=6 in each). The control group were administered saline solution sc, and the D-galactose group were administered 5% D-galactose solution sc at dose of 100 mg?kg -1. After 3 month, the rats were killed by exsanguination from heart. The fourth lumber vertebra was taken and immerged in formalin. The testicle were taken and immerged in formalin at the same time. The blood serum was collected by centrifugating the collected blood after resting for a while, and it was preserved in refrigeratory at the degree of - 70 ℃.The vertebra body were embedded in plastic and sliced up after being dehydrated step by step with different concentration ethanol. The slices were analyzed under the image analysis apparatus. The testicle were made into paraffin slices and observed under the common microscope. The concentration of serum testosterone and luteinizing hormone were measured by radio-immunity assay. RESULTS: The lumber vertebra body in D-galactose group appeared osteoporosis. The serum testosterone hormone concentrations of D-galactose rats were significantly decreased. And the microstructure of testicle present aging change, but no change of serum LH concentration was observed. CONCLUTION: D-galactose can cause the osteoporosis in male rats, which may be related to affect the function of thalamus-pituitary-testicle axis, decrease the content of testosterone of D-galactose.

STUDIES ON DISTRIBUTION OF FSH, LH AND COLOCALIZATION WITH GnRHR IN RAT SUBMAXILARY GRANDS / 解剖学报

Objective To investigate the distribution of folliclestimulating hormone (FSH),luteinizing hormone (LH) and colocalization with gonadotropin releasing hormone receptor (GnRHR) in rat submaxilary glands. Methods Distribution of FSH, LH and colocalization with GnRHR consecutive sections of rat submaxilary glands were investigated by immunohistochemical colocalization methods. Results FSH and LH immunoreactivity were observed in the epithelial cells of serous acinus, secretory tubes, excretory ducts and granular convoluted tubule. The immunoreactive materials were brown and distributed in the cytoplasma with negative nucleolus. The results of immunohistochemical colocalization showed not only FSH but also GnRHR immunoreactivity in the same structure of two adjacent section. The distribution of the positive substance of FSH and GnRHR were similar to each other. The most of showing GnRHR immunoreactivity cells were detected LH immunoreactivity in the same structure of two adjacene section and the others were immunonegative. The GnRNR immunoreactive materials were distributed in the cytoplasma with negative nucleolus.Conclusion The epithelial cell of serous acinus, secretory tubes, excretory ducts and granular convoluted tubule of rat submaxilary glands may be synthesized and secreted FSH and LH. These cells with FSH and LH positive immunoreaction of rat submaxilary glands may be regulated by Gonadotropin releasing hormone (GnRH) through autocrine or paracrine.;

Regulation of Steroid Thyroid Hormone Receptor 3 (TR3) mRNA Expression by Luteinizing Hormone in Human Early Luteinized Granulosa Cells / 대한산부인과학회잡지

OBJECTIVE: The present study examined the gonadotropin regulation of TR3 gene expression by luteinizing hormone (LH) in cultured human luteinized granulosa cells. METHODS: TR3 mRNA levels were detected by competitive reverse transcriptase-polymerase chain reaction (RT-PCR) method in cultured human luteinized granulosa cells collected from patients undergoing in vitro fertilization. RESULTS: TR3 transcript was transiently induced by LH, reaching maximum levels 1 hr after stimulation, in a dose-dependent manner. LH-stimulated TR3 expression was abolished by actinomycin D, but was superinduced by cycloheximide. Treatment of luteinized granulosa cells with Rp-cAMP, an inhibitor of protein kinase A, as well as, chelerythrin, an inhibitor of protein kinase C, suppressed LH-stimulated TR3 mRNA levels. In addition, forskolin and TPA mimicked the LH action on the induction of TR3 gene, implying the role of protein kinase A and C activation. CONCLUSION: Taken together, the present study demonstrates that TR3 gene was rapidly and transiently induced by LH in human luteinized granulosa cells. The results imply that TR3 may play a role in ovulation by initiating a cascade of ovulation-specific gene expression in response to LH.

PREDICTION OF OVULATION BY MEASURING URINARY LUTIENIZING HORMONE / 中华内分泌代谢杂志

Diagnostic laparoscopy was carried out 24-72 hours after urinary luteinizing hormone (LH) surge in 54 patients Estradiol (E2) concentration was determined by radioimmunoassay (RIA) in peritoneal fluid and serum Serum progesterone (P) in midluteal phase was determined by RIA.The reliability of predicting ovulation by means of LH surge was evaluated according to the laparoscopic finding of ovulation and the measurements of E2-RIA and P-RIA.Typical findings of ovulation - corpus hemorrhagicum, ovulatory stigma and bloody fluid in cul-de-sac - were observed during laparoscopy in 44 patients among 54 cases with LH surge. Ovulation was confirmed directly by laparoscopy in 44 patients (81.5%). Ovulation was confirmed by combination of laparoscopy and E2 ratio in 47 cases (87%). Predictive rate of LH surge for ovulation and corpus luteum formation was 87% and 98% respectively. Only one patient could not be confirmed to have ovulation and corpus luteum formation by LH surge.Luteinizing hormone enzyme immunoassay (LHEIA) can be started from the 10th day of menstrual cycle without missing the LH surge. LHEIA can be started from the 12th day of cycle in most patients.