Gonadotroph and corpus luteum responses to two successive intranasal doses of a luteinizing hormone-releasing hormone agonist at different days after the midcycle luteinizing hormone surge

Two successive intranasal doses (300 micrograms at 8:00 A.M. and 6:00 P.M.) of the luteinizing hormone-releasing hormone (LH-RH) agonist (D-Ser[TBU]6-des-Gly-NH2(10))LH-RH ethylamide (Buserelin) were administered on days 1 to 10 after the midcycle luteinizing hormone (LH) surge in 33 normally cycling women. Maximal stimulation of gonadotropins was observed at 4 hours and was of higher amplitude in the first 2 days after the LH surge. The response to the second dose was markedly blunted, showing pituitary refractoriness. On each day of treatment there was a progressive increase of serum estradiol, which was maximal (threefold) 4 hours after the second dose of Buserelin. Serum progesterone (P) levels were not significantly changed on days 1 to 4, but they were increased by 50% at 10 hours on days 5 to 10. Daily blood samples revealed that following treatment on days 1 to 4 after the midcycle LH surge, serum P profiles were lower than in control cycles, without change in the length of the luteal phase. Starting on treatment day 5, a precocious luteolysis was induced, as illustrated by an early fall in serum P levels and shortening of the luteal phase (1 to 4 days). All posttreatment control cycles were normal. The results of this time study indicate that an appropriate treatment with an intranasal Buserelin administered at any time between days 1 to 10 after the midcycle LH surge impair luteal function and could lead to a new postcoital contraceptive approach.     

Sensitivity of pituitary and corpus luteum responses to single intranasal administration of (D-ser[TBU]6-des-gly-NH2(10)) luteinizing hormone-releasing hormone ethylamide (Buserelin) in normal women

We have previously shown that intranasal administration of Buserelin (Hoechst AG, Frankfurt, Germany) at mid-luteal phase inhibits progesterone secretion and shortens the luteal phase. In order to determine the best possible use of this medication, we studied the effect of increasing doses (50 to 1500 microgram) of the luteinizing hormone-releasing hormone (LH-RH) agonist administered between days 6 and 12 after the luteinizing hormone (LH) peak on the pituitary response and corpus luteum function. A near-maximal gonadotropin response was obtained at a dose of 200 microgram. Maximal LH stimulation was observed at 4 hours, and serum levels of the hormone remained elevated for at least 14 hours at the two highest doses. Maximal serum follicle-stimulating hormone (FSH) levels were usually observed 2 hours later than for LH, and the response was longer lasting. A 2- to 2.5-fold stimulating of serum progesterone levels was observed at 8 hours for all doses studied. There was a tendency for a dose effect on serum estradiol levels, a 2-fold stimulation being obtained at 14 hours at the highest dose of LH-RH analog. Up to 200 microgram, there was no apparent change in the luteal phase. At the 500-microgram dose, there was a clear tendency for decreased estradiol and progesterone concentrations during the treatment cycle, while at 1000 and 1500-microgram doses steroid levels were clearly inhibited and the luteal phase was shortened by 2.5 days. Posttreatment cycles were normal. Thus the corpus luteum is sensitive to a single high intranasal dose of Buserelin, the luteolytic effect being related to the prolonged gonadotropin response.     

Luteal phase deficiency after completely normal follicular and periovulatory phases

Luteal phase defect (LPD) accounts for a significant proportion of reproductive disorders, however its etiology is still debated. A prospective study was performed on 37 ovulatory women to determine whether LPD can occur in cycles characterized by completely normal folliculogenesis. Criteria for normal folliculogenesis included: a gradual rise of serum estradiol, a luteinizing hormone (LH) surge, the presence of a dominant follicle that disappeared, an increase of serum progesterone, and normal serum levels of prolactin, testosterone, dehydroepiandrosterone sulfate, follicle-stimulating hormone, and LH. Thirty of 37 women fulfilled the above mentioned strict criteria and underwent endometrial biopsy in the late luteal phase. Seven of 30 (23%) demonstrated a delay in endometrial development and all had normal hormonal and ultrasonographic parameters of folliculogenesis and ovulation. Women with delayed endometrial development demonstrated slightly longer follicular phases (17.0 +/- 1.1 versus 14.5 +/- 0.3 days). Perfectly normal follicular and periovulatory events may be followed by deficient luteal phases.     

Effects of the antiprogesterone RU486 in the early follicular phase of the menstrual cycle

To investigate the role of progesterone (P) in the early follicular phase, the antiprogesterone effect of RU486 was examined in five normally cycling women monitored by daily hormonal levels during three consecutive cycles (control, treatment, and recovery). In addition, luteinizing hormone (LH) pulse characteristics were assessed by frequent blood sampling (10 minutes for 10 hours) on day 3 of the control and the corresponding day of treatment cycles. Administration of RU486 (3 mg/kg, orally) for the first 3 days of the menstrual cycle did not significantly alter the length of the follicular phase (13.4 +/- 1.7 to 15.2 +/- 1.3 days), the LH surge, or the luteal phase length (12.2 +/- 0.5 to 12.6 +/- 0.7 days). The intermenstrual length of the treatment cycle (29.8 +/- 1.9 days) did not differ from the control (27.6 +/- 1.8 days) or recovery cycles (29.6 +/- 2.5 days). Integrated secretion of P and estradiol (E2) did not vary during the luteal phase of the control, treatment, or recovery cycles. During RU486 treatment, LH pulse frequency, pulse amplitude, and mean LH were not altered. Whereas mean E2 levels were significantly decreased from 150.5 +/- 15.1 to 110.1 +/- 7.0 pmol/L, follicle-stimulating hormone, P, adrenocorticotropin hormone, and cortisol were not significantly altered. Thus, in spite of the transient decrement in E2 secretion during RU486 treatment, the integrity of the ovulatory menstrual cycle was maintained. We conclude that administration of the antiprogesterone RU486 at the dose used during the first 3 days of the follicular phase does not perturb menstrual cyclicity.     

Luteolytic activity of LHRH and [D-Ser(TBU)6, des-Gly-NH2(10)]LHRH ethylamide: a new and physiological approach to contraception in women

The administration of five subcutaneous 250-microgram doses of luteinizing hormone-releasing hormone (LHRH) at 4-hour intervals on 1 or 2 consecutive days between days 1 and 9 following the spontaneous LH surge in normal women shortened the luteal phase from 1 to 4 days in 16 out of 17 treatment cycles. Treatment appeared to be more efficient when LHRH was administered on days 6 to 9 after the LH surge as compared with days 1 to 5. In fact, the luteal phase was shortened from 3.3 +/- 0.2 versus 1.4 +/- 0.2 days (P < 0.01) and the serum progesterone level was decreased to 44 +/- 5 versus 71 +/- 6% of control levels (P < 0.01) when the neurohormone was injected late as compared with early in the luteal phase. A similar luteolytic effect has been obtained after intranasal administration of 500 microgram of [D-Ser(TBU)6, des-Gly-NH2(10)]LHRH ethylamide at 0800 and 1700 h on one day between days 4 and 9 following the LH peak. In six women treated with the LHRH analogue during two consecutive cycles, the luteal phase was shortened by 2.6 +/- 0.4 days (range 0.5-4.5 days) and plasma progesterone levels were reduced to 61.3 +/- 9.2% of control. As determined by daily blood sampling for LH, FSH, estradiol, and progesterone, normal cycles occurred immediately after treatment. The present data indicate the luteolytic effect of treatment with LHRH or a LHRH agonistic analogue in normal women and support the interest of such a new and physiological approach for the control of corpus luteum function and menstrual cycle in women.     

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.     

Inhibition of ovulation during discontinuous intranasal luteinizing hormone-releasing hormone agonist dosing in combination with gestagen-induced bleeding

Four groups of eight or nine normal cycling volunteers with regular menstrual cycles had daily blood sampling during two pretreatment, two treatment, and two posttreatment cycles. Intranasal doses of 100, 200, and 300 micrograms of (D-Ser[TBU]6-des-Gly-NH210) luteinizing hormone-releasing hormone (LH-RH) ethylamide were administered every 12 hours and compared with a 400-micrograms dose given every 24 hours during two periods of 21 days followed by a drug-free interval of 7 days. Five milligrams of medroxyprogesterone acetate was taken orally on days 17 to 21. Serum luteinizing hormone was elevated during the first 2 weeks of treatment, and serum follicle-stimulating hormone was increased only during the first 2 days of treatment. At 100 to 300 micrograms/12 hours serum estradiol was stimulated up to preovulatory levels, whereas at 400 micrograms/24 hours most values were in the early follicular phase range. Ovarian ultrasonography revealed the transient development of preovulatory-like follicles in 8 of 12 studied cycles. Serum progesterone values were less than 2 ng/ml in 57.3%, between 2 and 5 ng/ml in 27.9%, and greater than 5 ng/ml in 14.7%. Withdrawal bleeding occurred during the pause in 97% of treatment cycles. Nine of 13 breakthrough bleedings happened in the groups given 100-micrograms and 300-micrograms/12 hours. Recovery cycles showed slightly prolonged follicular phases with normal luteal phases. No changes were observed in routine laboratory measurements. In conclusion, intermittent administration of appropriate LH-RH agonist dosing in combination with a progestogen would effectively block ovulation while preserving adequate cyclic estradiol secretion and could be an alternative contraceptive approach.     

Ultrasonographical assessment of follicular growth in delayed ovulation

The growth of the follicle was monitored in 61 subjects by ultrasonography and by the serial determinations of serum LH, FSH, estradiol (E2) and progesterone. All the subjects were judged to have normal luteal functions on the basis of their BBT patterns. The subjects were divided into two groups according to the length of their follicular phase: one with a follicular phase of 12--17 days (the control group, 39 cycles) and the other with a follicular phase of 18--26 days (the delayed ovulation group, 22 cycles). Ultrasonographically, the follicle grew slowly during the early follicular phase (slow growing phase), but began to grow more rapidly at 7 or 8 days before ovulation (rapid growing phase). In comparison with the control group, the slow growing phase was significantly prolonged in the delayed ovulation group. But in the length of the rapid growing phases and follicular growth rate, there were no significant differences between the two groups. In the serum levels of E2, LH, FSH and P, there were no significant differences between the two groups.     

Response of ovarian steroid secretion to the intrinsic gonadotropin release caused by the administration of a synthetic luteinizing hormone-releasing hormone--the difference between the follicular and luteal phases

During gynecologic laparotomy both ovarian and peripheral venous blood specimens were collected simultaneously, and follicle-stimulating hormone (FSH), luteinizing hormone (LH), pregnenolone (P5), 17 alpha-hydroxypregnenolone (17 alpha-OH-P5), dehydroepiandrosterone (DHA), progesterone (P4), 17 alpha-hydroxyprogesterone (17 alpha-OH-P4), delta 4-androstenedione (delta 4-A), estradiol (E2) and 20 alpha-dihydroprogesterone (20 alpha-OH-P4) were measured in each sample by means of the radioimmunoassay technique before and after the administration of synthetic LH-releasing hormone (LH-RH). Significantly higher concentrations of P5, 17 alpha-OH-P4 and E2 during the follicular phase and that of P5, DHA, P4, 17 alpha-OH-P4 and E2 during luteal phase were observed in the ovarian than in the peripheral venous blood. During the follicular phase, P5, DHA and E2 concentrations in ovarian vein blood increased significantly following LH-RH administration. It was observed that the delta 4-steroids and E2 concentrations during the luteal phase were higher than those during the follicular phase. During the luteal phase P4, 17 alpha-OH-P4, and E2 increased after LH-RH administration. Enzymes involved in the formation of these steroids may be stimulated by the intrinsic gonadotropin caused by LH-RH administration. The difference in steroidal profiles in ovarian vein blood and response to LH-RH in follicular and luteal phase were demonstrated.     

The corpus luteum: determinants of progesterone secretion in the normal menstrual cycle

Fourteen normal volunteers were studied during one menstrual cycle. Follicular development, the luteinizing hormone (LH) surge, and the relationship between LH and progesterone secretion in the luteal phase were studied to determine the factors that control corpus luteum function. Follicular development was assessed by measuring follicle size and daily estradiol (E2) levels; the LH surge was quantified by determining the area under the curve. Although there was a significant positive correlation between mean follicle diameter and E2, these same parameters did not correlate with postovulatory progesterone secretion; nor did the LH surge correlate with progesterone secretion. A decrease in LH pulse frequency occurred in moving from the follicular to the luteal phase. There was a trend toward an increase in the late luteal LH pulse frequency compared with the midluteal phase, but this was not significant. Progesterone was secreted in an intermittent (pulsatile) fashion in the midluteal and late luteal phases. The general decrease in progesterone in the latter days of the menstrual cycle appears to be due to a decrease in the progesterone pulse amplitude. A significant correlation between LH and progesterone was present when the data were "smoothed"; however, there was not a significant synchrony for LH and progesterone pulses for most of the subjects when the initial data were analyzed by objective criteria. Progesterone secretion in the luteal phase is quite complex and leads to highly variable serum levels of progesterone when samples are obtained at random from normal women.     

Subtle abnormalities in follicular development and hormonal profile in women with unexplained infertility

A prospective study of six unselected couples diagnosed as having unexplained infertility was done. In three of six patients, subtle abnormalities in follicular development were detected. In the first case poor follicular growth was observed. There was a premature small rise of luteinizing hormone (LH) with subsequent low levels of estradiol (E2) in the late follicular phase and unusual wide LH peak. This was followed by low progesterone levels in the luteal phase. In the second case follicular growth was abrupted by premature LH surge. This surge was triggered by early rise of E2 level while the follicle was still small in size. In the third case luteinized unruptured follicle syndrome was diagnosed, on ultrasound examination. All of the abnormalities were repetitive.     

Response of ovarian steroid secretion to the intrinsic gonadotropin release caused by the administration of synthetic luteinizing hormone-releasing hormone

During gynecologic laparotomies, both ovarian and peripheral venous blood specimens were collected simultaneously, and follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol, and progesterone were measured in each sample by means of the radioimmunoassay technique before and after the administration of synthetic LH-releasing hormone (LH-RH). The FSH levels rose significantly 30 minutes after the LH-RH injection, while the LH values had already increased significantly at 15 minutes. A significant decrease of the average FSH and LH levels during the follicular phase and of the average LH levels during the luteal phase was observed in the ovarian as compared to the peripheral venous blood. The estradiol levels in the ovarian venous blood made a prompt and significant increase almost in parallel with the gonadotropin release. During the luteal phase, the progesterone concentrations in the ovarian and peripheral venous blood increased significantly. It is considered that the human ovary responds quite promptly to an abrupt release of intrinsic FSH and LH caused by the administration of synthetic LH-RH and secretes estradiol and progesterone immediately.     

Effect of clomiphene citrate on follicular and luteal phase luteinizing hormone concentrations in in vitro fertilization cycles stimulated with gonadotropins and gonadotropin-releasing hormone antagonist

OBJECTIVE: To investigate the effect that clomiphene citrate exerts on luteinizing hormone (LH) concentrations in gonadotropin/gonadotropin-releasing hormone (GnRH) antagonist cycles. DESIGN: Retrospective analysis. SETTING: Tertiary referral center. PATIENT(S): Two groups of patients undergoing in vitro fertilization (IVF) were compared. In group I, 20 patients were stimulated with clomiphene citrate (CC) in combination with gonadotropins and 0.25 mg of Cetrorelix (ASTA Medica AG; Frankfurt am Main, Germany) and in group II, 20 patients were stimulated with gonadotropins and 0.25 mg of Cetrorelix. INTERVENTION(S): Blood sampling was performed in the late follicular, periovulatory, early, mid, and late luteal phases. MAIN OUTCOME MEASURE(S): Luteinizing hormone (LH), estradiol, and progesterone. RESULT(S): LH levels were significantly higher in group I than in group II on all the days studied. Progesterone serum concentrations were significantly higher in group II in the early luteal phase, but not in the follicular or the middle and late luteal phases. CONCLUSION(S): LH concentrations are significantly higher in the follicular and luteal phases in cycles stimulated with CC, despite GnRH antagonist administration. This observation might have implications for the dose of GnRH antagonist needed to suppress LH in the follicular phase and questions the need for luteal-phase supplementation in cycles in which CC was used.     

Ultrasonic study of follicular maturation, ovulation and development of corpus luteum during normal menstrual cycles

Ovarian follicular growth, ovulation and development of corpus luteum was monitored with ultrasound in 29 normal menstrual cycles in 14 women. Results were correlated to changes in serum estradiol, LH and progesterone levels. The follicles reached a maximum diameter of 20.5 +/- 2.70 mm (mean +/- SD) with an intercycle variation of 16 to 25 mm, and growth rates ranged between -2 and 6 mm from the day before the LH peak to the day of the LH peak. Cumulus echoes were observed in all follicles with a maximum diameter of more than 17 mm and the cumulus appeared from 1 to 3 days before ovulation. On the day after the LH peak, the follicle was still present in two cycles and had disappeared from 15 cycles. In 11 cases different morphologic patterns could be visualized at the former sites of the follicles. In the middle of the luteal phase the mature corpus luteum was seen as an echogenic area in 16 cases and as a cyst in 1 case.     

Vaginal progesterone administration in physiological doses normalizes raised luteinizing hormone levels in patients with polycystic ovarian syndrome.

A raised luteinizing hormone (LH) level is a typical finding in the polycystic ovarian syndrome (PCOS). This inappropriate elevation of LH is thought to interfere with normal follicular development and ovulation. The resulting chronic anovulation is associated with the absence of the luteal phase increase in secretion of progesterone and inhibin. Progesterone can exert both a positive and negative feedback action on LH secretion, but inhibition is thought to occur following prolonged exposure to progesterone. Therefore, the aim of this study was to see if exogenously administered progesterone in physiological doses would normalize circulating LH concentrations in patients with PCOS. Vaginal progesterone was administered twice daily in a dose of 100 mg, at 12 h intervals, to ten women with PCOS. Serum samples were taken on alternate days for radioimmunoassay of follicle stimulating hormone (FSH), LH, estradiol, progesterone and inhibin. To determine the effect of progesterone on LH secretory dynamics in PCOS, LH pulse studies were carried out prior to treatment, and on day 10 of progesterone administration in four of the ten subjects. Mean serum progesterone concentrations reached 51 nmol/l by 4 days after exogenous progesterone treatment, and remained in the mid-luteal phase range, as established in 12 normal cycles, during the use of the vaginal suppository. The mean serum LH concentration had fallen significantly (p < or = 0.01) after 8 days of treatment, and continued to fall progressively until the end of progesterone administration. Serum LH concentrations had fallen into the normal follicular phase range by 14 days (mean 5.5, range 3.4-10.9 IU/l; normal follicular phase range 1.8-10.0 IU/l).(ABSTRACT TRUNCATED AT 250 WORDS)     

Possible luteolytic effects of luteinizing hormone-releasing hormone in normal women.

The administration of five subcutaneous 250-microgram doses of lutienizing hormone (LH)-releasing hormone (LHRH) at 4-hour intervals, the first injection being given at 8 A.M. on 1 or 2 consecutive days between days 1 and 9 following the LH surge in normal women, shortened the luteal phase from 1 to 4 days in 16 of 17 treatment cycles. There was a better efficiency of treatment when LHRH was administered on days 6 to 9 after the LH surge as compared with days 1 to 5. In fact, the luteal phase was shortened from 3.3 +/- 0.2 days versus 1.4 +/- 0.2 days (P less than 0.01) and the serum progesterone level was decreased to 44% +/- 6% versus 71% +/- 6% of control levels (P less than 0.01) when the neurohormone was injected late as compared with early in the luteal phase. The present data raise the possibility of a luteolytic effect of LHRH in normal women and indicate the interest of such a near-physiologic approach for the control of luteal function and time of appearance of menses.     

Follicular phase treatment of luteal phase dysfunction

Previously, we demonstrated that selective suppression of serum follicle-stimulating hormone (FSH) in monkeys treated with charcoal-extracted porcine follicular fluid (pFF) in the early follicular phase induced luteal defects resembling those which occur spontaneously in women and monkeys. Here, we assessed whether luteal phase defects arising in association with induced FSH deficiencies during the early follicular phase can be treated by early FSH therapy. Rhesus monkeys were treated with pFF and human menopausal gonadotropin (hMG) (FSH:luteinizing hormone [LH], 3:1) on cycle days 1 to 3 or day 4, respectively. Daily femoral blood samples were analyzed for LH, FSH, and estradiol by radioimmunoassay. In the monkeys treated with the pFF-hMG combination, a single ovulation was uniformly noted at laparoscopy, and initial luteal phase elevations in serum progesterone levels were nearer those of normal ovulatory cycles than after pFF alone. These results suggest that FSH/LH treatment in the early follicular phase compensated, in part, for the pFF-induced deficiency in endogenous FSH levels.     

Potential new treatment of endometriosis: reversible inhibition of pituitary-ovarian function by chronic intranasal administration of a luteinizing hormone-releasing hormone (LH-RH) agonist

This paper reports on the case of a 30 year old woman suffering from pelvic endometriosis, dyspareunia, and postcoital bleeding. The patient was treated for 173 days, starting on the 7th day of the cycle, with intranasal administration of 300 mcg of Buserelin, a luteinizing hormone-releasing hormone (LH-RH) agonist, every 12 hours. During the treatment period basal luteinizing hormone (LH) and estradiol (E2) levels were measured at various time intervals. Buserelin caused a marked inhibition of pituitary and ovarian function 2 weeks after inception of treatment. Basal LH levels were low, and serum E2 levels were decreased below those usually found in the early follicular phase. The hormonal inhibition lasted for the entire treatment period, and the only side effects were hot flashes. After 2 months of treatment dyspareunia and postcoital bleeding had almost disappeared; laparoscopy at the end of treatment showed a marked regression of endometrial lesions. Ovulation returned spontaneously after only 43 days of treatment, and regular menstrual cycles appeared shortly after termination of treatment. This prompt return to normal ovarian function should be particularly advantageous for patients seeking pregnancy. This study shows that LH-RH treatment could be a valuable approach for the medical treatment of endometriosis; however, this is only a preliminary report, and further investigation is needed before it can be safely stated that LH-RH agonist is an effective drug for the longterm treatment of endometriosis.     

Inhibition of the primate ovarian cycle by a porcine follicular fluid protein(s)

Monkeys received twice daily intramuscular injections of 3 mg of purified porcine follicular fluid protein(s) for the first 14.5 days of the menstrual cycle. Two of five treated monkeys had anovulatory menstrual cycles. Three monkeys had cycles characterized by long follicular phases, low follicular and luteal phase serum estradiol concentrations, and subnormal luteal progesterone production. Serum gonadotropin concentrations were not affected by the follicular fluid protein(s). The data demonstrate in the nonhuman primate that porcine follicular fluid contains a protein(s) that acts at the ovarian level to inhibit gonadotropin action.     

Studies on inhibin in human follicular fluid

In order to investigate whether inhibin (FSH-suppressing activity) is present in human follicular fluid (hFF) and whether inhibin in hFF could be correlated with the FSH level in peripheral serum, the effect of hFF on FSH secretion was studied using monolayer culture of rat anterior pituitary cells. Dextran-coated charcoal (DCC)-treated hFF exerted an inhibitory effect on pituitary FSH secretion but not on LH. The inhibitory effect of hFF upon basal FSH secretion was different from those of steroids such as estradiol, progesterone, testosterone and androstenedione. hFF inhibited the LHRH-stimulated secretion of both FSH and LH. Since hFF and porcine follicular fluid (pFF) produced a parallel dose-dependent decrease of basal FSH secretion, the same suppressing activity may be present in both hFF and pFF. Inhibin activity increased gradually during the follicular phase, but decreased in the luteal phase. Inhibin activity in hFF except during preovulatory surge showed a significant inverse correlation with the FSH level in peripheral serum. These results might indicate that inhibin activity in hFF increased according to follicular maturation and that inhibin (non-steroidal substance) may be one of the important regulators of FSH secretion in the human pituitary.