Limitations of follicle-stimulating hormone in assessing menopause status: findings from the National Health and Nutrition Examination Survey (NHANES 1999-2000)*

OBJECTIVE: We used data from the National Health and Nutrition Examination Survey (NHANES 1999-2000) to: establish new population-based estimates for follicle-stimulating hormone (FSH) and luteinizing hormone (LH); identify factors associated with FSH; and assess its efficacy in distinguishing among women in the reproductive, menopause transition, and postmenopausal stages. DESIGN: Nationally representative sample of 576 women aged 35 to 60 years examined during NHANES 1999-2000. RESULTS: Levels of FSH and LH increased significantly with reproductive stage. (Geometric mean FSH levels for successive stages: reproductive, 7.0 mIU/mL, SE 0.4; menopause transition, 21.9 mIU/mL, SE 3.7; and postmenopause, 45.7 mIU/mL, SE 4.3). There was considerable overlap, however, among distributions of FSH by stage. Only age and reproductive stage were significantly associated with FSH in multivariable analysis. FSH cutoff points between the reproductive and menopause transition stages [FSH = 13 mIU/mL, sensitivity 67.4% (95% CI 50.0-81.1), specificity 88.1% (95% CI 81.1-92.8)] and between the menopause transition and postmenopause stages [FSH = 45 mIU/mL, sensitivity 73.6% (95% CI 60.1-83.7), specificity 70.6% (95% CI 52.4-84.0)] were neither sensitive nor very specific. CONCLUSIONS: Age and reproductive stage are the most important determinants of FSH levels in US women; however, FSH by itself has limited utility in distinguishing among women in different reproductive stages.     

Monitoring reproductive aging in a 5-year prospective study: aggregate and individual changes in luteinizing hormone and follicle-stimulating hormone with age

OBJECTIVE: This study describes age-related changes in luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in a 5-year prospective study of reproductive aging. DESIGN: Participants (n = 156 college-educated, white, US women; 25 to 58 y) were recruited from the TREMIN Research Program on Women's Health. They collected daily urine specimens for 6 months in each of 5 consecutive years. Specimens were assayed for LH and FSH. Aggregate changes were calculated in LH and FSH with age, and multilevel models were used to estimate individual hormone trajectories and within-woman and between-woman variances by age. RESULTS: Aggregate LH levels increased beginning after age 45; FSH increased at all ages, accelerating after age 45. Individual-level patterns with age included the following: reproductive-age LH and FSH levels, with increasing FSH and increasing or decreasing LH (ages 20 to 49); rapidly increasing LH and FSH (ages 40 to 59); and increasing or steady postmenopausal LH and FSH (ages 46 to 62). FSH levels were consistently high in the latter category, but LH levels overlapped with levels found in younger women (<45 y). Individual LH patterns showed more variability (5% to 35% of total variance) than FSH (3% to 22% of total variance). Both hormones had relatively low variation within individuals compared with between-woman differences (65% to 97% of total variance). CONCLUSIONS: Aggregate-level data do not reflect differences across women and oversimplify the age-related increases and variability in LH and FSH. Individual FSH levels are not distinguishable from reproductive-age levels until after rapid perimenopausal increases in FSH occur; individuals vary in whether their postmenopausal LH levels are distinguishable from reproductive-age levels.     

Analysis of serum levels of anti-Mullerian hormone, inhibin B, insulin-like growth factor-I, insulin-like growth factor binding protein-3, and follicle-stimulating hormone with respect to age and menopausal status

This study was undertaken to investigate age-dependent and postmenopausal changes in the serum levels of anti-Mullerian hormone (AMH), inhibin B, insulin-like growth factor (IGF)-I, IGF-binding protein-3 (IGFBP-3), and follicle-stimulating hormone (FSH), and to determine which of these markers best reflects the aging process in women. A total of 144 women aged 20-59 yr were enrolled in this cross-sectional study. Blood samples were obtained on cycle day 3 of regularly menstruating women (n=111), or at random in postmenopausal women (n=33). Data were analyzed with respect to premenopausal women age groups and compared in pre- and postmenopausal women. Area under the receiver operating characteristic curve (ROCAUC) analyses were performed to assess the ability of each marker to discriminate between the pre- and postmenopausal status. Serum levels of AMH, IGF-I, and IGFBP-3 decreased and serum levels of FSH increased significantly with age in premenopausal women. Serum luteinizing hormone (LH) was higher and inhibin B was lower in women in their 20-30's than in 40's. Serum levels of AMH and IGF-I showed a consistent decrease with all age groups. ROCAUC analysis showed that the diagnostic accuracy of AMH for menopausal status was similar to those of FSH, LH, and inhibin B, and was better than that of IGF-I. In conclusion, the serum AMH level appears to be the best marker of the aging process in premenopausal women.     

卵泡刺激素与卵泡刺激素及黄体生成素共同干预对玻璃化冻存小鼠卵巢组织血管内皮生长因子表达的影响

目的 通过在玻璃化冻存全程给予小鼠卵巢组织卵泡刺激素（FSH）及FSH和黄体生成素（LH）共同干预,观察冻融卵巢组织的形态学改变以及两种激素干预对冻存卵巢组织血管内皮生长因子（VEGF）表达的影响,寻找最佳的提高冻融卵巢组织卵泡存活及VEGF表达的激素干预方式。 方法 4周龄C57BL/6J小鼠卵巢组织分为新鲜对照组（CG）,玻璃化冻存对照组（VCG）,300IU/L FSH全程干预玻璃化冻存组（OG-FSH）,以及150IU/L FSH+150IU/L LH全程干预玻璃化冻存组(OG-FSH+LH),每组30个卵巢样本。通过常规组织学、Western blotting技术,观察并分析各组卵巢组织形态结构改变及VEGF蛋白表达量;通过荧光定量PCR技术(Real-time PCR)检测VEGF mRNA表达情况。 结果 OG-FSH+LH 组正常卵泡百分比最高,且显著高于OG-FSH组（P<0.05）;VEGF蛋白表达量在OG-FSH+LH组显著高于OG-FSH组（P<0.05）;荧光定量PCR检测结果表现为VEGF mRNA表达量在OG-FSH+LH组最高,其次为OG-FSH组,最低是VCG组（P<0.05）。 结论 玻璃化冻存全程添加FSH+LH的干预方式较单独FSH干预具有更高正常卵泡百分比和更佳的VEGF蛋白表达。     

Endocrine and follicle characteristics of cycles with and without endogenous luteinizing hormone surges during superovulation induction with pulsatile follicle-stimulating hormone

The induction of superovulation in women with human gonadotrophinsmay result in blockage of the endogenous luteinizing hormone(LH) surge, but the reasons for this are not known. Ten normallyovulating women with longstanding infertility volunteered forthis study. They were treated with 225 IU follicle-stimulatinghormone (FSH) daily s.c. in a pulsatile manner (28 IU every3 h) starting on cycle day 2. Serum FSH and oestradiol levelsincreased and serum LH levels decreased significantly duringthe FSH treatment, as compared to their spontaneous cycles.Only five women displayed an LH surge during the FSH treatment.Serum FSH and LH levels during treatment were significantlylower and the number of follicles 12–15 mm in diameterand their total fluid volume was significantly greater in thecycles without an endogenous LH surge. Basal LH levels in thecycles without an LH surge increased soon after the end of theFSH treatment (cycle day 18), while FSH levels were still verylow without any incremental tendency. These results suggestthat a high number of small follicles may have a suppressiveeffect on both tonic and mid-cycle gonadotrophin secretion.Furthermore, the LH suppressive mechanism seems to be differentfrom that of the FSH.     

Pituitary—ovarian relationships in women approaching the menopause

With a view to evaluating pituitary-ovarian relationships in women approaching the menopause, serial determinations of basal body temperature (BBT) and of serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH) and oestradiol were performed in 5 pre-menopausal and 9 young women throughout a complete menstrual cycle. The hormone levels in the early follicular phase and on LH peak-days in the two groups were then compared. In the pre-menopausal group the age range was 43–45 yr and the length of the menstrual cycles investigated varied from 30–56 days, the BBT curves being biphasic.Two pre-menopausal women demonstrated concentrations of FSH and LH that were higher than those in the young women, even though their serum oestradiol levels in the early follicular phase remained within the upper and lower mean values observed in the young women.This finding confirmed that, in addition to reduced ovarian oestrogen secretion, another, as yet unknown, factor must exist, which can produce a rise in serum gonadotrophin levels in women approaching the menopause.     

A study on the effects of interaction between naloxone and 2-Br-alpha-ergocryptine or clonidine on luteinizing hormone, follicle-stimulating hormone, prolactin and thyroid-stimulating hormone levels in normal man serum.

The effects of 2-Br-alpha-ergocryptine (2.5 mg/osM), clonidine (50 microgram, intramuscularly) and naloxone (0.4 mg, intramuscularly) as well as the interaction between naloxone and 2-Br-alpha-ergocryptine or clonidine on luteinizing hormone (LH) follicle-stimulating hormone (FSH), prolactin (PL) and thyroid-stimulating hormone (TSH) serum levels in normal man have been studied. 2-Br-alpha-ergocryptine and clonidine clearly reduce and naloxone tends to reduce PL serum levels. TSH levels are lowered by naloxone as well by clonidine plus naloxone. The results obtained point also to a possible different pattern of LH and FSH secretion after naloxone, that is after opiate receptor blockade. The clonidine effects on PL secretion are discussed in the frame of a possible adrenergic control of the release of this hormone.     

Effect of delta-opioid receptor agonist deltorphin on circulating concentrations of luteinizing hormone and follicle stimulating hormone in healthy fertile women

There is evidence that endogenous opioid peptides exert an inhibitory effect on pituitary luteinizing hormone (LH) secretion both in animals and in humans, by interacting with mu-opioid receptors. However, a role for delta-opioid receptors in the regulation of gonadotrophin releasing hormone (GnRH) secretion has recently been suggested. In the present study, we evaluated the effect of the highly selective delta-opioid receptor agonist deltorphin on the LH and follicle stimulating hormone (FSH) responses to naloxone in six healthy fertile women during the luteal phase of the menstrual cycle. Deltorphin infusion alone (7 microg/kg/min for 60 min) did not significantly change the basal serum concentrations of LH in this group of women. The intravenous (i.v.) bolus administration of naloxone (15 mg) induced a significant (P < 0.001) increase in serum LH concentrations (from a mean basal value of 4.24+/-1.10 IU/l to a peak of 13.27+/-1.8 IU/l). The LH response to naloxone was significantly (P < 0.001) blunted by preinfusion of deltorphin (13.27+/- 1.80 IU/l versus 4.80+/-1.18 IU/l). No significant changes in FSH concentrations were observed during deltorphin, naloxone or deltorphin plus naloxone administration. These data indicate that activation of delta-opioid receptors can reduce naloxone-induced LH release, suggesting a possible role of delta receptors in opioidergic modulation of LH secretion in women.      

Endocrinology: Recombinant human follicle-stimulating hormone and ovarian response in gonadotrophin-deficient women

Seven women suffering from hypogonadism due to previous hypophysectomy,isolated gonadotrophin deficiency, or Kallman's syndrome [medianage 39 years (range 24–45)] volunteered to participatein a study to assess ovarian response following multiple-doseadministration of recombinant human follicle-stimulating hormone(rhFSH; Org 32489). Baseline serum FSH and luteinizing hormone(LH) concentrations were 0.25 (<0.05–1.15) IU/l and0.06 (<0.05–0.37) IU/l, respectively. Subjects receiveddaily i.m. injections of rhFSH for 3 weeks (week 1: 75 IU/day,week 2: 150 IU/day, week 3: 225 IU/day). Blood sampling andsonographic investigations were performed on alternate days.Steady-state FSH concentrations were reached 3–5 daysafter alterations of the doses administered. Maximum FSH concentrationswere between 7.1 and 11.8 IU/l, whereas serum LH concentrationsremained unchanged. Due to absent follicle development and lackof a rise in immunoreactive inhibin (INH) (response failurepossibly due to early ovarian failure or resistant ovary syndrome)in two subjects, analysis of ovarian response was restrictedto five volunteers. Serum androstenedione levels showed no significantchanges during rhFSH administration. Although serum immunoreactiveINH concentrations reached normal late follicular values [659(388–993) IU/l], serum oestradiol revealed only a minorincrease [77 (18–210) pmol/I]. Moreover, growth of (multiple)ovarian follicles was observed up to pre-ovulatory sizes (>15mm) in these patients. It may be concluded from the presentstudy that (i) rhFSH exhibits no intrinsic LH activity; (ii)rhFSH stimulation in hypogondotrophic women resulted in an immunoreactiveINH rise which was similar to that in normal women, whereasin contrast only a minor increase in oestradiol concentrationswas observed (suggesting normal granulosa cell function andlow availability of androgens as a substrate for aromatization);(iii) despite the minimal oestrogen increase, ovarian folliclesdeveloped normally to the pre-ovulatory stage.     

Utility of follicle stimulating hormone (FSH), luteinizing hormone (LH), oestradiol and FSH:LH ratio in predicting reproductive age in normal women

The relative efficacy of follicle stimulating hormone (FSH), luteinizing hormone (LH), FSH:LH ratio and oestradiol is evaluated as a predictor of ovarian reserve (reproductive age) in normal women. Serum levels of FSH, LH, oestradiol and FSH:LH ratios were measured during menstrual cycle days 1-4 in younger (20-25 years; n = 23) and older (40- 45 years; n = 32) reproductive age women with regular menstruation and normal reproductive function. On days 1-4, mean levels of FSH, oestradiol and FSH:LH ratios were significantly higher in older compared with younger women. FSH increased in concentration across cycle days in both age groups. A significantly lower LH value in younger versus older women was found only on day 1. Oestradiol showed no change across days in the younger group, but increased significantly from day 1 to day 4 in the older group. FSH values on days 1 or 2 were the best single predictor of age differences. However, the best prediction of age differences was obtained by using the combination of FSH and LH (as opposed to the FSH:LH ratio) on day 1 of the menstrual cycle.      

Recognition of gonadotroph adenomas in women

BACKGROUND. Pituitary adenomas that arise from the gonadotroph cells are being recognized with increasing frequency in men, but they are still rarely recognized in women. This rarity could be the result of an actual difference in occurrence or of greater difficulty in recognition. The tumors are usually recognized in men more than 50 years old, but elevated serum gonadotropin levels in women of that age could be produced by normal gonadotroph cells. METHODS. Because the stimulation of follicle-stimulating hormone (FSH), luteinizing hormone (LH), and the beta subunit of LH (LH beta) by thyrotropin-releasing hormone (TRH) is a characteristic of gonadotroph adenomas in men, we administered TRH to 16 women with apparently nonsecreting pituitary macroadenomas and measured serum FSH, LH, LH beta, and the glycoprotein hormone alpha subunit every 15 minutes for 90 minutes before and 90 minutes after. The results were compared with the responses in 16 healthy women matched for age and in 10 women with macroadenomas secreting prolactin, growth hormone, or corticotropin. The tumors from 12 of the women with nonsecreting adenomas were cultured, and the secretion of FSH, LH, and LH beta in culture was determined. RESULTS. Eleven of the 16 women with apparently nonsecreting adenomas had significant increases in serum LH beta in response to TRH, 3 had FSH responses, and 4 had LH responses. None of the 16 healthy women and none of the 10 women with secreting macroadenomas had LH beta, FSH, or LH responses to TRH. Ten of the 12 adenomas that were cultured secreted readily detectable amounts of FSH, LH, and LH beta, and their secretion in vitro correlated with the patients' responses to TRH in vivo. CONCLUSIONS. Most apparently nonsecreting pituitary macroadenomas in women arise from gonadotroph cells. The majority of these can be recognized, even in postmenopausal women, by the serum LH beta responses to TRH, and some can be recognized by the responses of serum FSH and LH.     

Reevaluation of the roles of luteinizing hormone and follicle-stimulating hormone in the ovulatory process.

Circulating levels of luteinizing hormone (LH) are essential for the production of steroid hormones that regulate the timing of ovulation and target tissue responses, as well as maintenance of the corpus luteum and therefore early pregnancy. Clinical and basic science observations show that elevated levels of serum LH during the follicular phase of the menstrual cycle are not only unnecessary for follicular maturation but are deleterious to normal reproductive processes. These elevations may occur as a result of administration of exogenous LH or through an endogenous pathological process (i.e. polycystic ovarian disease, PCOD). Resting levels of LH, synergizing with locally produced IGFs, inhibin and perhaps other growth factors, are adequate for normal follicular growth and steroidogenesis. Elevations in serum LH above these resting levels may result in increased androgen production that diminishes follicular function and reduces early embryo viability. Elevated LH levels during the preovulatory period may also negatively influence post-ovulatory events such as conception and implantation. With these facts in mind, the best results for ovulation induction would be expected with purified follicle-stimulating hormone (FSH) administration to women following gonadotrophin releasing hormone (GnRH) down-regulation. It is hoped that this review provides the reader with an analysis of the complex series of events that regulate normal follicular maturation. The reevaluation of the two cell-two gonadotrophin theory suggests that during the preovulatory period, resting levels of LH are adequate for normal follicular maturation. Indeed, overstimulation of the ovary with excessive amounts of LH may diminish the ability of that target organ to produce fertile ova.(ABSTRACT TRUNCATED AT 250 WORDS)     

Serum levels of gonadotrophins and steroid hormones in the post-menopause and later life

Changes in the serum levels of gonadotrophins and steroid hormones with increasing age were studied in 449 women aged 40 and over to investigate the relationships between these hormones even very late in life. The levels of oestradiol (E2) and dehydroepiandrosterone sulphate (DHEA-S) fell after age 50 and remained low thereafter. However, while serum oestrone (E1), testosterone (T), delta-4-androstenedione (A) and prolactin (PRL) concentrations also decreased initially after age 50 they subsequently rose again progressively and this increase was in fact significant in the case of E1. Luteinizing hormone (LH) and follicle-stimulating hormone (FSH) rose after age 50, but whereas FSH remained elevated, LH decreased late in life. Cortisol (F) increased significantly after age 70. There was a significant correlation between androgens and E1 as well as between E2 and LH, even after age 60. Owing to the great heterogeneity of the population studied, it is not yet possible to speculate as to the physiopathological significance of these observations. It would seem, however, that the negative feedback effect of oestrogens on LH secretion remains operational very late in life.     

Effect of the ratio of follicle-stimulating hormone to luteinizing hormone on rat granulosa cell proliferation and oestradiol-17 beta secretion.

The present study examined the effects of the ratio of follicle-stimulating hormone (FSH) to luteinizing hormone (LH) on granulosa cell proliferation and oestradiol-17 beta secretion. For these studies, ovarian segments from either immature rats or those primed with pregnant mares serum gonadotrophin (PMSG) were incubated for 5 h with [3H]thymidine and FSH (0-100 mIU/ml) with or without equivalent doses of LH. After incubation, granulosa cells were isolated and their mitotic activity estimated by determining the amount of [3H]thymidine incorporated into the DNA. The amount of oestradiol secreted into the media was measured by radioimmunoassay. Compared to granulosa cells from immature ovaries, granulosa cells from PMSG-primed ovaries required significantly less FSH to stimulate incorporation of [3H]thymidine, had a 9-fold higher basal level of oestradiol production and increased oestradiol secretion in response to gonadotrophins. At pharmacological serum levels (10-20 mIU of total gonadotrophin), FSH:LH ratios of less than or equal to 2 increased oestradiol secretion from PMSG-primed ovaries but did not increase the rate of [3H]thymidine incorporation. Conversely, FSH:LH ratios of greater than or equal to 3 stimulated [3H]thymidine incorporation without altering oestradiol secretion. These data demonstrate that granulosa cells of immature follicles not secreting oestradiol are relatively unresponsive to gonadotrophins at any dose tested. Once the capacity for oestradiol secretion develops, then both the dose and ratio of FSH and LH play major roles in determining whether the follicle will grow or secrete oestradiol.     

Positive feedback effect of oestradiol in superovulated women.

To investigate the mechanism of blockage of the luteinizing hormone (LH) surge in superovulated women, six normally ovulating women were studied in three cycles: a spontaneous cycle treated with exogenous oestrogen (oestradiol benzoate cycle), a cycle treated with follicle stimulating hormone (FSH; 225 IU/day; FSH cycle) and a cycle treated with FSH plus exogenous oestrogen (FSH + oestradiol benzoate cycle). Oestradiol benzoate was injected i.m. on cycle days 4 (0800 and 2000 h), 5 (0800 h) and 6 (0800 h) at doses of 0.5, 1.0, 2.0 and 2.5 mg respectively to achieve supraphysiological levels of serum oestradiol. Exogenous oestrogen (supraphysiological oestradiol levels) induced an LH surge in all six women in the oestradiol benzoate cycles, but failed to stimulate an LH surge in three of the six patients during treatment with FSH. In three patients treated with FSH, an LH surge was stimulated both by supraphysiological (FSH + oestradiol benzoate cycles) and 'high normal' oestradiol levels (FSH cycles), while in three patients treated with FSH only, the LH surge was blocked, although the threshold level for the positive feedback effect had been exceeded by cycle day 9. We conclude that in women, supraphysiological concentrations of oestradiol exert a positive feedback effect on LH secretion. It is suggested that the occurrence of an LH surge in cycles superovulated with FSH is not dependent on serum oestradiol concentrations, but mainly on the strength of ovarian inhibitory substances.     

Long-term effect of a first pregnancy on the secretion of prolactin

An early first pregnancy is known to protect against subsequent breast cancer. We speculated that this effect may be mediated by a long-term depression of prolactin secretion after pregnancy. We therefore measured basal and post-stimulation serum levels of prolactin, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) in two groups--15 women 18 to 23 years of age and 9 women 29 to 40--before and after a first full-term pregnancy, and in 40 appropriate nulliparous controls. We observed no significant change in basal levels of serum LH or FSH or in the levels stimulated by gonadotropin-releasing hormone in any group. A significant decrease was seen, however, in basal and perphenazine-stimulated levels of prolactin after pregnancy in both the younger and older first-pregnancy groups but not in the controls. In a separate cross-sectional study, we compared basal serum prolactin levels in 29 parous and 19 nulliparous women of similar age. The serum prolactin levels were significantly lower in the parous group but were not related to the number of pregnancies (one to three) or the time elapsed (12 to 150 months) since the last delivery. We conclude that a first pregnancy leads to a long-term decrease in serum prolactin secretion, lasting at least 12 to 13 years.     

Blunted prolactin response to exogenous luteinizing hormone releasing hormone in superovulated women

To investigate the prolactin (PRL) response to luteinizing hormone releasing hormone (LHRH) in superovulated cycles, eight normally ovulating women were studied in two cycles, i.e. a spontaneous (control) and a cycle treated with 'pure' follicle stimulating hormone (FSH) (225 IU/day). LHRH was given to the women i.v. (a single injection of 100 micrograms) in the late follicular phase of both cycles. The oestradiol levels (mean +/- SEM) at the time of the LHRH challenge were 635 +/- 31 and 1707 +/- 225 pmol/l respectively (P less than 0.001). The size of the leading follicle was similar in both cycles. Basal PRL levels (mean +/- SEM) on the day of the LHRH experiment were significantly higher in the FSH (250 +/- 31 microIU/ml) than in the spontaneous cycles (133 +/- 15 microIU/ml. P less than 0.05). In the latter cycles, LHRH induced a significant increase in serum PRL and LH levels, while the FSH cycles, the prolactin (PRL) response to LHRH was blunted and LH response markedly attenuated. We conclude that superovulation induction stimulates basal but suppresses LHRH-induced PRL release. It is suggested that basal PRL secretion is LHRH-independent and the suppressing effect is mediated via previously described paracrine interactions between the gonadotrophs and lactotrophs and/or through ovarian inhibitory substances.     

The effect of recombinant follicle stimulating hormone (Gonal-F) on endogenous luteinizing hormone secretion in women

Parenteral administration of follicle stimulating hormone (FSH) has been shown to lower luteinizing hormone (LH) concentrations in women undergoing ovulation induction. This study was designed to explore the physiological mechanism of this effect. Seven healthy women were recruited into a double-blind placebo-controlled study. LH secretion, after the administration of variable i.v. boluses (37.5, 75 and 150 IU) of recombinant FSH (Gonal-F), was evaluated. LH was measured at 10 min intervals for 2 h before and 4 h after the FSH/placebo infusion. LH pulse frequency and amplitude were evaluated and there was no significant difference between control and trial cycles for each subject. A linear regression analysis revealed that in the group receiving 150 IU FSH, the mean plasma LH concentration decreased significantly due to a reduction tonic LH secretion. This could be a result of the suppression of secretion or an alteration of clearance. This decrease was not seen in the other dosage groups, revealing that above a dosage threshold, FSH reduced non-pulsatile LH secretion. Therefore the effect of FSH in this study exposed the likely presence of two components of LH concentration: an FSH-sensitive, non-pulsatile tonic secretion and a gonadotrophin-releasing hormone-stimulated, pulsatile release that is unaffected by FSH. Although an indirect effect involving ovarian regulation is not excluded, the rapidity of the effect suggests that FSH acts directly on the pituitary gland.      

Effect of follicle stimulating hormone treatment on the pituitary response to luteinizing hormone-releasing hormone in post-menopausal women

To study the role of exogenous follicle stimulating hormone(FSH) in the attenuation of luteinizing hormone (LH) responseto luteinizing hormone-releasing hormone (LHRH) during ovulationinduction in women, 10 healthy post-menopausal women were treatedwith FSH (225 IU/day) for 5 days and normal saline (2 ml/day)for another 5 days. The two regimens were given consecutivelyin a 10 day experiment. The regimen for the first 5 days wasrandomly chosen and was given to the women in an alternate way.The response of LH to an i.v. injection of 10 µg LHRHwas investigated twice on day 1 (i.e. before the onset of treatmentand 12 h later) and once on days 2, 5 and 10 of the experiment(0900 h). Basal FSH and LH values before the onset of treatmenton day 1 were similar in the five women who started with thesaline and the five who started with the FSH regimen. BasalFSH values increased significantly during treatment with FSH,while LH and oestradiol values remained unchanged throught thewhole experiment. LH increment 30 min post –LHRH did notchange significantly either during the first 24 h or duringthe whole experiment regardless of the starting regimen. Theseresults demonstrate that in post-menopausal women the responseof LH to LHRH is not affected by exogenous administration ofFSH. It is suggested that exogenous FSH does not show activitieson gonadotrophin secretion similar to those ascribed to a gonadotrophinsecretion similar to those ascribed to a gonadotrophin surgeattenuating factor.     

Ontogeny of sex differences in LH and FSH levels 48 h after castration in the rat

Serum gonadotropin levels were measured 12, 24, and 48 h after gonadectomy in male and female rats (ages, 22--60 days) to assess when during development the rate of rise of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) after castration approximates that seen in the gonadectomized adult. In females serum LH levels 48 h after ovariectomy were increased above sham levels only when the ovaries were removed prior to vaginal opening. Ovariectomy on the day of vaginal opening or at older ages resulted in no increase in LH levels by 48 h after surgery. Serum FSH levels at 24 and 48 h after ovariectomy declined with increasing age at the time of ovariectomy. In males serum LH levels at 48 h after castration increased with increasing age at the time of gonadectomy. Serum FSH levels at either 12, 24, or 48 h after orchidectomy did not change appreciably with age at the time of surgery. It is concluded that the acute pituitary secretion of gonadotropins after removal of testes in the immature male resembles that seen in the mature male early in the course of the development of sexual maturity. In contrast, the acute pituitary secretion of gonadotropins after removal of the ovaries in the immature female does not resemble that seen in the ovariectomized adult until she is mature and capable of ovulating. Thus, the observed delay in the rise of LH seen in ovariectomized adults may be a function of some aspect of the hormonal changes associated with the estrous cycle.