Is the inappropriate gonadotropin secretion of patients with polycystic ovary syndrome similar to that of patients with adult-onset congenital adrenal hyperplasia?

OBJECTIVE: To assess gonadotropin alterations in adult-onset congenital adrenal hyperplasia (CAH) and to compare these findings with those of patients with polycystic ovary syndrome (PCOS) in an effort to better understand the pathophysiology of these abnormalities. DESIGN: Prospective study of 9 newly diagnosed patients with CAH, 10 with PCOS, and 10 ovulatory controls. INTERVENTIONS: Baseline measurements of serum androgens, progestins, estradiol (E2), estrone (E1), unbound E2, luteinizing hormone (LH), and follicle-stimulating hormone (FSH). Serum LH and FSH were measured after intravenous gonadotropin-releasing hormone (GnRH) and in 15-minute blood samples for 6 hours to determine LH pulsatility. RESULTS: Serum androgens were elevated but comparable in the two patient groups. Serum LH was also elevated (P less than 0.05) but was higher in PCOS than CAH. Serum LH:FSH ratios were similar as were the responses to GnRH. Serum E1 was elevated only in PCOS, but unbound E2 was elevated to the same degree in both PCOS and CAH (P less than 0.05). Patients with PCOS had a decreased LH interpulse interval compared with controls and CAH (P less than 0.05), but LH pulse amplitude was increased in both PCOS and CAH (P less than 0.05). Serum E2 and unbound E2 correlated significantly with LH (P less than 0.05), LH responses to GnRH as well as to LH pulse amplitude in CAH (P less than 0.05). The LH interpulse interval did not correlate with estrogen in any group. None of the LH parameters correlated with serum progestin levels in CAH. CONCLUSIONS: The gonadotropin abnormalities of CAH appear to be intermediate between those of controls and PCOS. Although elevated estrogen may explain these abnormalities in CAH, additional factors may be operative in PCOS.     

Three types of polycystic ovarian syndrome in relation to androgenic function

OBJECTIVE: To re-evaluate the concept of polycystic ovarian syndrome (PCOS) in view of androgenic function. DESIGN: Patients were studied endocrinologically and ultrasonographically. SETTING: This study was performed as a clinical investigation. PATIENTS, PARTICIPANTS: Sixty-nine euprolactinemic anovulatory patients with luteinizing hormone (LH) hypersecretion and 18 normal volunteers were selected. INTERVENTIONS: One hundred micrograms of LH-releasing hormone were administered. MAIN OUTCOME MEASURE(S): It was possible to divide PCOS patients into three types. RESULTS: Patients with neither hirsutism nor elevation of serum androstenedione (delta 4) and/or testosterone (T) were designated as type I PCOS (n = 20). Patients without hirsutism but with elevated delta 4 and/or T were referred to as type II PCOS (n = 33). Patients with both hirsutism and elevation of delta 4 and/or T were defined as type III PCOS (n = 16). Concentrations of delta 4 appeared gradedly increasing in types I, II, and III in that order, whereas T concentrations were significantly higher in types II and III than in control. Ultrasonographically, cystic ovaries were found in 88%, 84%, and 100% of types I, II, and III patients, respectively. CONCLUSIONS: It is postulated that each type may represent a subset of whole spectrum of PCOS from Stein-Leventhal syndrome to simple anovulation with LH hypersecretion.     

Primary polycystic ovary syndrome in a premenarchal girl. A case report

A 12-year-old, premenarchal girl with hirsutism and virilization of nine months' duration was found to have highly elevated serum testosterone and a radiologic evaluation suggestive of bilaterally enlarged ovaries with a solid left ovarian mass. Serum gonadotropins were normal, with an LH:FSH ratio of 2:1. Exploratory laparotomy showed bilaterally enlarged polycystic ovaries, confirmed by wedge biopsies. No ovarian tumor was found. Oral contraceptives decreased the total serum testosterone to the normal female levels within three months. This was one of the youngest reported patients with primary polycystic ovary syndrome.     

Peripheral catecholamine metabolites and free testosterone in patients with polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) is characterized by chronic anovulation, elevated serum estrogen and androgen levels, and inappropriate gonadotropin secretion. The present study compares the androgen levels (free testosterone) and catecholamine metabolites (DOPAC as a marker of central dopaminergic activity, DOPEG as one of adrenergic activity) in patients with PCOS and normal controls. The mean serum LH and free testosterone levels of polycystic ovary patients were significantly higher than those of normal controls. The mean DOPEG/DOPAC ratio in the polycystic ovary patients was significantly higher than those of the control group and there was a significant correlation between free testosterone and DOPEG or the DOPEG/DOPAC ratio. It is suggested that, in vivo, norepinephrine excess is present in women with PCOS and that a hyperandrogenemic status is correlated with catecholamine activity.     

Polycystic ovary syndrome: an endocrine and metabolic disease.

Polycystic ovary syndrome (PCOS) is a common disorder occurring during female reproductive years, characterized by a number of heterogeneous clinical and biochemical features. Clinical presentation is characterized by hirsutism, acne, androgen-dependent alopecia, menstrual dysfunction, infertility and ultrasonographically-documented cystic ovaries. Tonic elevation of luteinizing hormone (LH) secretion is a regular feature of PCOS. Abnormal secretion of estrogen and high serum levels of free testosterone are also present. In addition to these endocrine abnormalities, specific metabolic alterations, such as hyperinsulinemia and insulin resistance are more frequent. Metabolic derangements associated with PCOS may predispose the patient to a range of diseases with attendant morbidity and mortality risks, so it is important to consider the syndrome in terms of both endocrine and metabolic aspects, achieving a correct hormone equilibrium and preventing metabolic alterations.     

Induction of LH surge with estradiol benzoate and its clinical significance in anovulatory women

In order to investigate the hypothalamic function of anovulatory women serial determinations of the serum gonadotropins (LH and FSH) were made over a period of 120 h following the intramuscular injection of 1 mg of estradiol benzoate (E.B.). Ten women with normal menstrual cycles and 57 anovulatory women were subjected to this study. The positive release of LH in serum (exceeding at least 150% of basal level) in response to E.B. was noted in follicular phase of the cycles, but not in luteal phase, and in 31 of 57 patients the release came between 48 to 96 h after the E.B. injection. The LH surge after E.B. injection was difficult to provoke when the basal serum LH and estradiol (E2) levels were low: less than 10 mIU/ml and 50 pg/ml, respectively. Thirteen of 27 patients, who showed LH surge, ovulated because of Clomid. Only three of 17 patients, who did not show LH surge, ovulated as a response to Clomid. Ten of 14 patients, who showed LH surge after E.B. but did not ovulate after Clomid, revealed a polycystic ovarian disease (PCO), and the responsiveness to both E.B. and Clomid improved after wedge-resection of the ovaries. These results suggest that the serum E2 level is closely correlated to the ability for LH-RH production in the hypothalamic "surge center," and that the E.B. provocation test is useful for investigating the hypothalamic function of anovulatory women and for diagnosing preoperatively the PCO resistant to Clomid treatment.     

正常卵巢与多囊卵巢的颗粒细胞E_2和P的产生及其卵泡液中E_2和雄烯二酮(A)含量的比较

为了解正常卵巢与多囊卵巢(PCO)颗粒细胞功能的异同.本研究对12例正常人卵泡期的25个卵泡和7例PCO的约60个卵泡的颗粒细胞进行了培养,用放免法测定卵泡液中雌二醇(E_2)和雄烯二酮(A)及培养液中E_2和孕酮(P)的含量.结果表明PCO的颗粒细胞对FSH和LH刺激更敏感,产生更多的E_2和P.FSH(10ng/ml)作用下PCO组产生的E_2和P分别比正常组高8.8倍(P<0.001)和2.6倍(P<0.05).LH(10ng/ml)作用下PCO组产生的E_2和P也分别高4.8倍(P<0.01)和2.0倍(P>0.05);PCO卵泡液中A的含量明显高于正常对照(P<0.05).PCO的颗粒细胞甾体激素合成酶的活性增高,可能是PCOS病人的高LH和高INS血症起关键作用.     

PCOS患者药物促排卵中LUFS发生的相关因素

目的 探讨多囊卵巢综合征(PCOS)患者药物诱导排卵治疗中发生未破裂黄素化卵泡综合征(LUFS)的相关因素。方法 对比克罗米酚(CC)及人绝经后促性腺激素(HMG)方案用药前后PCOS患者血清PRL、FSH、LH、E_2、T水平,阴道超声检查卵巢形态,分析PCOS患者LUFS发生与基础性激素水平和卵巢形态的关系。结果 应用CC加用HCG45例,卵泡发育率66.67％,周期妊娠率为22.22％,LUFS发生率33.33％;应用CC无效者,应用HMG方案30例,卵泡发育率高(86.67％),但LUFS和过度刺激综合征(OHSS)发生率高分别为36.67％和13.33％,周期妊娠率16.67％。T水平LUFS组高于排卵组,表明LUFS的发生与血清睾酮水平有关。周边囊泡型多囊卵巢(PCP)LUFS发生率25％,普通囊泡型多囊卵巢(GCP)LUPS发生率75％。结论 普通囊泡型多囊卵巢患者易于发生卵泡黄素化不破裂综合征,可能与患者雄激素水平相对较高,卵巢包膜厚,优势卵泡不是发生在卵巢周边有关。     

Polycystic ovary syndrome: evolution of a concept.

Despite improved diagnostic facilities and advanced in vitro studies, the primary causes of the polycystic ovary syndrome (PCOS) have not been resolved. In addition to certain enzyme deficiencies causing a PCOS-like state, current evidence indicates altered functions of 5 alpha-reductase and cytochrome P450c17 alpha in PCOS patients as a group. However, it is not obvious if these are primary or secondary to the abnormal hormonal milieu. The relation of insulin-like growth factors (IGFs) to PCOS is of particular interest in view of the occurrence of IGF-II mRNA in the granulosa cells and the ability of IGF-I to regulate the granulosa cell and thecal-interstitial cell functions. In obese PCOS patients, the levels of sex hormone binding globulin and IGF-binding protein-1 are subnormal in serum, and fasting increases them. Fasting also suppresses high insulin and IGF-I concentrations in the same women. Growth hormone, regulated by insulin and probably by IGF-I, appears to be decreased in PCOS patients. Follicular growth, characteristically arrested in PCOS, is regulated by growth hormone to some extent, and growth hormone treatment has been found to improve the ovarian response to gonadotropins in some but not all anovulatory patients. In addition to the administration of growth hormone itself, therapeutic measures modulating the growth hormone-ovarian axis are being studied. High serum luteinizing hormone levels are typical of PCOS. These are often associated with infertility and early pregnancy loss. Lowering of the luteinizing hormone levels by a gonadotropin-releasing hormone analogue in combination with gonadotropins improves the outcome of pregnancies as compared with those achieved by clomiphene citrate. The use of the former regimen in PCOS patients may result in ovarian hyperstimulation. Ovarian electrocautery has proved to be effective in restoring cyclicity of ovarian function with a concomitant fall in luteinizing hormone and androgen levels. Interestingly, an increase in serum insulin secretion has been noted. It remains to be elucidated if this therapy, followed by decreased luteinizing hormone, is effective in reducing the elevated risk of miscarriages in women with PCOS.     

Laparoscopic ovarian drilling in polycystic ovary syndrome

BACKGROUND AND OBJECTIVE: Patients with polycystic ovary syndrome (PCOS) treated with gonadotrophins often have a polyfollicular response and are exposed to the risks of ovarian hyperstimulation syndrome (OHSS) and multiple pregnancy. The aim of the present study was to evaluate the efficacy of laparoscopic ovarian drilling (LOD) on the endocrinologic, clinical parameters and reproductive outcome of clomiphene-resistant anovulatory infertile patients with PCOS using monopolar diathermy. MATERIAL AND METHODS: Forty-five clomiphene-resistant anovulatory women with PCOS have participated in the study. Serum testosterone (T), follicle stimulating hormone (FSH) and luteinizing hormone (LH), fasting insulin and glucose levels, body mass indexes, modified Ferriman Gallwey (FG) hirsutism scores of the subjects are recorded before and after the procedure. Endocrinologic and clinical profile and reproductive outcome of the patients were analysed. RESULTS: Ovarian drilling was successfully employed without any surgical complications and mean +/- S.D. duration of follow-up time was 29.73 +/- 10.64 months. In the follow-up period 93.3% of the subjects were recorded to have regular cycles and 64.4% pregnancy rate was achieved, spontaneously. The serum levels of T, free T, LH, LH:FSH ratio, insulin and FG scores were significantly reduced after LOD, although glucose levels and glucose/insulin ratio remained unchanged. CONCLUSION: In choosing ovulation induction method in clomiphene resistant PCOS patients, LOD may avoid or reduce the risk of OHSS and multiple pregnancy than gonadotrophins with the same success rate of conception. The high pregnancy rate, and economic aspect of the procedure offer an attractive management for patients with PCOS.     

Primum Non Nocere

Surgical ovarian wedge resection was the first established treatment for women with anovulatory polycystic ovary syndrome (PCOS) but was largely abandoned both due to the risk of postsurgical adhesions and the introduction of medical ovulation induction. Laparoscopic ovarian drilling (LOD) is an alternative method to induce ovulation in PCOS patients with clomiphene citrate resistance instead of gonadotropins. Surgical therapy with LOD may avoid or reduce the need for gonadotropins or may facilitate their use. However, the procedure, though effective, can be traumatic on the ovaries, which may cause postoperative adhesions and/or diminished ovarian reserve. In over-enthusiastic hands, this day-care procedure might lead to iatrogenic premature ovarian failure in young women. Some trials have compared LOD with gonadotropins, but, because of variations in study design and small sample size, the results are inconsistent and definitive conclusions about the relative efficacy of LOD and gonadotropins cannot be extracted from the individual studies. Today, evidence-based reviews conclude that there is no evidence of a significant difference in rates of clinical pregnancy, live birth or miscarriage in women with clomiphene-resistant PCOS undergoing LOD compared to other medical treatments. The reduction in multiple pregnancy rates in women undergoing LOD is the only pro-LOD argument. However, there are ongoing serious concerns about the long-term effects of LOD on ovarian function.     

Definition of polycystic ovary syndrome

This article aims to answer two questions in defining polycystic ovary syndrome (PCOS): what is PCOS and how should the syndrome be recognized in clinical practice? Whether PCOS is a primary or a secondary ovarian disease remains controversial. It has been suggested for many years that the main pathophysiological factor in PCOS is dysregulation of the relationship between the hypothalamus, the pituitary and the ovary. However, PCOS also involves intraovarian morphological and functional abnormalities. With respect to clinical practice, many reports have questioned the sensitivity as well as the specificity of a high LH concentration. Similarly, the biological hyperandrogenism of PCOS cannot define the syndrome. GnRH agonist or hCG tests are not convenient for the diagnosis of PCOS in practice. Stromal hyperplasia is considered to be indicative of PCOS but it is highly dependent on the settings of the ultrasound machine, thus use of the total ovarian area, the upper normal limit of which is 5.5 cm(2), is recommended. The need for diagnostic markers of PCOS depends on the clinical presentation. In the full-blown syndrome (classic PCOS), the clinical symptoms provide the most powerful indication and the association of the three components (hyperandrogenism, anovulatory dysfunction and metabolic abnormalities) has a strong diagnostic potency. In non-classic PCOS, a cost-effective and safe work-up should be applied, which includes ultrasonography and hormonal assays (basal serum concentrations of testosterone, sex hormone binding globulin, 17-hydroxyprogesterone, LH, FSH and prolactin). Asymptomatic PCOS may be discovered incidentally during ultrasonography, and it is important to take this finding into account when designing an ovulation induction protocol. In most cases of PCOS, the diagnosis may remain presumptive providing other diagnoses have been ruled out and the follow-up does not disclose any atypical development of the condition.     

Relationships between circulating leptin concentrations and other hormonal parameters in obese and non-obese women with polycystic ovary syndrome

Aim: To clarify the role of leptin in women with polycystic ovary syndrome (PCOS), we analyzed whether serum leptin levels correlate with other hormonal parameters in obese and non-obese women with PCOS.
Methods: We studied 20 obese (body mass index, BM ≥25 kg/m²) and 20 non-obese (BMI <25 kg/m²) women with PCOS diagnosed by the existence of menstrual disturbance, elevated serum level of luteinizing hormone (LH) with normal follicle-stimulating hormone (FSH) and the characteristic polycystic appearance of the ovaries on transvaginal ultrasound images. Blood samples for LH, FSH, estradiol, testosterone (T), androstenedione (Δ₄) and leptin were obtained, and the relationships between variables were examined by calculating Spearman correlation coefficients.
Results: Mean levels of leptin, T and Δ₄ in obese PCOS women were significantly higher than those in non-obese PCOS women, but this was not the case for BMI, bodyweight and waist to hip ratio. In all the 40 PCOS women considered together, there were significant positive correlations of leptin with BMI, waist to hip ratio, and Δ₄ levels. However, in each group separately, serum leptin levels in obese PCOS women correlated only with BMI and bodyweight, whereas serum leptin levels in non-obese PCOS women correlated with serum A4 levels.
Conclusion: Although further study is needed to assess the role of leptin on ovarian function in non-obese women with PCOS, present findings do not support the fact that leptin is involved in the development of hormonal abnormalities in obese women with PCOS. (Reprod Med Biol 2002; 1 : 49–54)     

Dynamics of bioactive follicle-stimulating hormone secretion in women with polycystic ovary syndrome: effects of estradiol and progesterone

OBJECTIVE: To determine the nature of bioactive FSH secretion in anovulatory women with polycystic ovary syndrome (PCOS) and its modulation by luteal levels of E2 and P. DESIGN: Interventional and observational study. SETTING: Academic clinical research center. PATIENT(S): Five patients with PCOS. INTERVENTION(S): Treatment for 21 days with luteal levels of E2 and P. MAIN OUTCOME MEASURES: Serum levels of immunoreactive LH, immunoreactive FSH, bioreactive FSH, and the FSH isoform distribution pattern. Blood was sampled frequently and GnRH testing was done on day 0 (before treatment), days 10 and 20 (during treatment), and day 28 (7 days after treatment). RESULT(S): Treatment with E2 and P suppressed circulating immunoreactive LH and immunoreactive FSH but not bioreactive FSH. Anovulatory women with PCOS showed a predominantly acidic pattern of FSH isoform distribution. Treatment with E2 and P shifted the distribution profile of FSH isoforms to the less acidic. After cessation of E2-P treatment, FSH reverted to its pretreatment pattern of distribution. CONCLUSION(S): Resumption of follicular growth after luteal replacement of E2 and P in anovulatory women with PCOS may be related to the reduction in the elevated LH/FSH ratio and accompanying changes in the FSH signal.     

Concentration of vascular endothelial growth factor released by cultured human luteinized granulosa cells is higher in women with polycystic ovaries than in women with normal ovaries

To test the hypothesis that increased serum levels of vascular endothelial growth factor (VEGF) in women with polycystic ovaries or the polycystic ovary syndrome (PCOS) result from excess release by ovarian granulosa cells.Prospective study.Academic research setting.Twenty women undergoing IVF treatment, of whom 10 had normal ovaries and 10 had polycystic ovaries.Human granulosa lutein cells were isolated from follicular fluid obtained on the day of oocyte retrieval. Release of VEGF was assessed after co-incubation of granulosa lutein cells with gonadotropins and insulin. Serum and follicular fluid concentrations of VEGF were measured.Release of VEGF from granulosa lutein cells and serum levels of VEGF.Incubation with human hCG, and luteinizing hormone increased release of VEGF into the culture medium. Insulin alone did not increase release of VEGF, but addition of insulin increased hCG-stimulated release of VEGF. Serum and follicular fluid VEGF concentrations and the amount VEGF released from granulosa lutein cells obtained from women with polycystic ovaries or PCOS and those who developed the ovarian hyperstimulation syndrome were greater than those from granulosa lutein cells obtained from women with normal ovaries and those who did not develop the ovarian hyperstimulation syndrome.The amount of VEGF released by granulosa lutein cells is gonadotropin dependent and is augmented by insulin. The increased circulating concentrations of VEGF in women with PCOS may not only be due to an increased number of actively secreting granulosa lutein cells but also due to increased secretory capacity of each granulosa cell.     

Diagnosis of polycystic ovary syndrome: from NIH criteria to ESHRE-ASRM guidelines

In the past, the diagnosis of polycystic ovary syndrome (PCOS) was based on National Institute of Health (NIH) criteria (hyperandrogenism and chronic anovulation) or on sonographic findings of polycystic ovaries. Diffe-rences in diagnosis criteria made it difficult to compare the data of studies coming from different countries. Moreover, there was criticism of both the methods used. In 2003, at a joint meeting of the European Society for Human Reproduction (ESHRE) and the American Society of Reproductive Medicine (ASRM), new guidelines for the diagnosis of PCOS were suggested. According to these guidelines, it is possible to reach a diagnosis of PCOS when at least 2 of these 3 elements are present: hyperandrogenism, chronic anovulation and polycystic ovaries. New criteria for the echographic diagnosis of polycystic ovaries have been suggested, too. These diagnostic guidelines represent important progress because they are more flexible and permit us to make the diagnosis in patients who were previously excluded by the syndrome (such as ovulatory hyperandrogenic women with polycystic ovaries or anovulatory normoandrogenic women with polycystic ovaries). However, doubts still exist and regard some borderline group of patients such as hirsute ovulatory normoandrogenic women with polycystic ovaries. A new classification of PCOS syndrome is suggested on the basis of new guidelines.     

Neuroendocrine control in polycystic ovary-like syndrome.

In this review article evidence is assembled from the neuroendocrinology of women with polycystic ovary-like syndrome (PCOS), to argue that the central dysregulation of gonadotropin secretion as found in the syndrome is not the cause of its development. The increased amplitude of luteinizing hormone (LH) pulses is explained by an increased pituitary sensitivity to gonadotropin releasing hormone (GnRH) due to prolonged unopposed estrogen exposure of the gonadotropic cells. The increase in pulse frequency cannot be used in the argument because it may be the cause for, as well the result of, the pathological status of the ovary. A good argument for a pathogenetic involvement of central factors, however, is the reversed day/night rhythm in adolescent girls with PCOS. A critical review of the literature does not give evidence of involvement of either obesity or catecholamines in the central abnormalities. Therefore they cannot cause PCOS via central feedback systems. The response of the gonadotropins to progesterone is the same as it is in normally cycling women. Androgens exert a variable effect on LH secretory patterns, although they do induce the typical change of PCOS in the ovaries. This argues for an ovarian rather than for a central cause. Endogenous opiates seem to be increased in PCOS. It can be argued that this should suppress both LH secretion and adrenal androgen secretion. It should also stimulate insulin-like growth factor (IGF)-binding proteins, thereby binding more IGF with less stimulatory action on the theca cells to produce androgens. Therefore endogenous opiates do not seem to be involved in the pathogenesis of PCOS either. Studies in PCOS during the recovery from GnRH agonist treatment show that the luteinizing hormone/follicle stimulating hormone (LH/FSH) ratio is quite normal for some time during the recovery phase. However, PCOS always develops again. This therefore does not give a clue either. In pulsatile GnRH stimulation of PCOS patients, the LH and FSH secretory patterns completely normalize. However, the symptoms of PCOS continue under this stimulation and the clinical pattern does not change dramatically. This gives the best argument that PCOS is caused by one or more peripheral factors, which may be ovarian in origin, rather than by central factors.     

The role of ultrasound in ovulation induction by gonadotropins

Fifty anovulatory women were selected for treatment with gonadotropins. Sixty-five were monitored by serum 17-beta estradiol (E2) levels and human chorionic gonadotropin was administered accordingly. Retrospective evaluation of cycles indicates that the overstimulation syndrome and the number of undesired multiple pregnancies can be reduced after both ovaries have been visualized by ultrasound if, regardless of E2 serum levels, human chorionic gonadotropin is administered when one or two mature follicles are seen and withheld when three or more mature follicles are seen.     

Therapeutic potentials of the natural plant flavonoid apigenin in polycystic ovary syndrome in rat model: via modulation of pro-inflammatory cytokines and antioxidant activity

Abstract

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women of reproductive age, which is associated with increased androgens, chronic inflammation, and oxidative stress. Current research aims at determining the effect of flavonoid apigenin on the level of antioxidant and anti-inflammatory factors in ovarian tissue of rats with PCOS. In this study, 32 female Wistar rats were divided into four groups (n?=?8): control, PCOS control, and treated groups (20 and 40?mg/kg apigenin). After 21 days of intervention, the serum levels of sex hormones and gonadotropins were measured. The ovarian tissue was removed for biochemical and histological studies. Research findings indicated that apigenin causes significant decrease in estrogen, testosterone levels, LH and LH to FSH ratio, and significant increase in progesterone and FSH levels in serum of treated groups compared to PCOS control group. Different doses of apigenin significantly decreased the inflammatory cytokines tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and total oxidative status (TOS). The total antioxidant capacity (TAC) and superoxide dismutase (SOD) activity significantly increased in treated groups compared to the PCOS control group. The histological results indicated that the number of cysts and theca layer thickness significantly decreased and the number of corpora lutea and granulosa layer thickness significantly increased in the rats receiving the apigenin as compared to the PCOS control group. Flavonoid apigenin through antioxidant and anti-inflammatory properties can be used as an alternative method for treating patients with PCOS.     

Alteration of follicle regulatory protein levels in human reproductive disorders: anovulation

Recently, a follicle regulatory protein was identified that suppresses ovarian response to gonadotropins. In this study, the serum levels of follicle regulatory protein were measured in five groups of women: reproductive age undergoing oophorectomy (N = 10), postmenopausal (N = 10), ovulatory (N = 13), anovulatory (N = 16), and anovulatory receiving clomiphene citrate therapy (N = 14). Follicle regulatory protein-related immunoreactivity was measured by a competitive enzyme-linked immunosorbent assay, while peripheral estradiol and progesterone levels were determined by established radioimmunoassay. Concentration of follicle regulatory protein in serum in all ovariectomized patients decreased significantly from preoperative levels. The postmenopausal women had significantly lower follicle regulatory protein levels than did ovulatory and anovulatory women. Patients with low levels of serum estradiol in the early follicular phase exhibited either significantly elevated or suppressed follicle regulatory protein levels compared with patients with normal estradiol concentrations, suggesting two different etiologies for ovarian dysfunction. Eleven to 12 and 22-23 days after the onset of the last menstrual period, patients with elevated follicle regulatory protein levels were found to be anovulatory. These observations suggest that elevated intraovarian levels of follicle regulatory protein may cause a disruption of follicular maturation that leads to anovulation and, in some cases, to resistance to clomiphene citrate therapy.