Variability of serum gonadotropin and dehydroepiandrosterone sulfate concentrations in women with polycystic ovary syndrome.

This study was designed to assess the variability of luteinizing hormone (LH), follicle-stimulating hormone (FSH) and dehydroepiandrosterone sulfate (DHEAS) levels over time in women with polycystic ovary syndrome (PCOS). Serum LH, FHS and DHEAS concentrations were determined for four consecutive monthly intervals in three groups of women: group 1, normal cycling women in the follicular phase (n = 9); group 2, normal cycling women in the luteal phase (n = 10); and group 3, women with PCOS (n = 11). For LH, DHEAS and the LH/FSH ratio, a histogram was constructed based on whether the subjects in each group had 0, 1, 2, 3 or 4 high values. In addition, the coefficient of variation (CV) for the four individual values of each hormone was determined for each subject to quantitatively assess the variability of measurement over time. Histographic analysis revealed that an elevated LH value or an elevated LH/FSH ratio in PCOS was inconsistent. For DHEAS, 9 of 11 PCOS subjects had either 0 (n = 7) or 4 (n = 2) high values, suggesting that such determinations are relatively consistent. We conclude that (1) isolated LH or LH/FSH measurements may not be sufficiently reproducible to be clinically useful despite evidence that LH values may be more stable in PCOS than in normal women and (2) a normal or high DHEAS value in PCOS is more likely to be consistently replicated, although the number of subjects studied limits the power of this conclusion.     

Pulsatile luteinizing hormone secretion in hypothalamic amenorrhea, anorexia nervosa, and polycystic ovarian disease during naltrexone treatment.

OBJECTIVE: To determine if chronic treatment with the long-acting oral opioid antagonist naltrexone can increase luteinizing hormone (LH) and follicle-stimulating hormone (FSH) secretion in women with secondary amenorrhea. DESIGN: Prospective. SETTING: Large reproductive endocrinology unit of an academic hospital. PATIENTS: Three groups of women with oligomenorrhea or amenorrhea: (1) hypothalamic amenorrhea; (2) anorexia nervosa; and (3) polycystic ovarian disease (PCOD). INTERVENTION: Naltrexone 50 mg every day for 4 days. MAIN OUTCOME MEASURES: Luteinizing hormone pulse pattern, frequency and amplitude, mean LH and FSH levels, measured by serial blood sampling over a 6-hour period before and after naltrexone. RESULTS: Naltrexone caused a significant increase (P less than 0.05) of the LH pulse frequency in patients with hypothalamic amenorrhea and in PCOD but not in anorexia nervosa. The mean levels of LH and FSH and LH pulse amplitudes were not significantly changed by naltrexone. The naltrexone nonresponders were underweight either because of simple weight loss or anorexia nervosa and had low levels of estradiol and an LH pulse pattern similar to the luteal one. CONCLUSION: The luteal LH pulse pattern in weight loss-related amenorrhea is caused by a nonopioid, undernutrition-linked factor.     

Neuroendocrine effects of androgens in adult polycystic ovary syndrome and female puberty

In addition to hyperandrogenism and ovulatory dysfunction, polycystic ovary syndrome (PCOS) is characterized by neuroendocrine abnormalities including a persistently rapid gonadotropin-releasing hormone (GnRH) pulse frequency. Rapid GnRH pulsatility favors pituitary secretion of luteinizing hormone (LH) over that of follicle-stimulating hormone (FSH). Excess LH stimulates ovarian androgen production, whereas relative deficits in FSH impair follicular development. The rapid GnRH pulse frequency is a result of reduced progesterone-mediated feedback inhibition of the GnRH pulse generator secondary to infrequent luteal phase increases in progesterone, as well as reduced hypothalamic sensitivity to progesterone feedback. Progesterone sensitivity is restored by treatment with the androgen receptor blocker flutamide. As such, hyperandrogenemia appears to play an important pathophysiologic role in PCOS. Adolescent hyperandrogenemia is believed to be a precursor to adult PCOS. In addition to increased LH concentrations and pulse frequency, some girls with elevated androgen levels also demonstrate reduced hypothalamic sensitivity to progesterone feedback. We hypothesize that excess peripubertal androgens may reduce the sensitivity of the GnRH pulse generator to sex steroid inhibition in susceptible individuals, resulting in increased GnRH pulse frequency and subsequent abnormalities in gonadotropin secretion, ovarian androgen production, and ovulatory function. Over time, these abnormalities may progress to the clinical hyperandrogenism and chronic oligo-ovulation typical of adult PCOS.     

Pulsatile intravenous gonadotropin-releasing hormone for ovulation-induction in infertile women. I. Safety and effectiveness with outpatient therapy

Pulsatile intravenous gonadotropin-releasing hormone (IV-GnRH) was used in 36 infertile patients with primary amenorrhea (n = 5), secondary amenorrhea due to hypothalamic chronic anovulation (HCA) (n = 22), hyperprolactinemia (n = 1) or polycystic ovary syndrome (PCOS) (n = 5), and oligomenorrhea (n = 3). Treatment was commonly initiated in the hospital but was then continued outside, with patients and local physicians accepting responsibility for maintaining IV-GnRH delivery systems. Twenty-eight of 113 treatment cycles (24.8%) resulted in pregnancy, with four spontaneous abortions (14.3%) and four twin pregnancies (16.7%) among 24 births. Probability of pregnancy per treatment cycle was significantly higher for primary amenorrhea (0.30) and for HCA (0.33) than for PCOS (0.07; P less than 0.05) and for oligomenorrhea (no conceptions; P = 0.01). Ovulatory cycles were not achieved in five patients (primary amenorrhea, n = 1; PCOS, n = 3; oligomenorrhea, n = 1). There were no serious complications; six patients recorded eight febrile episodes, which responded quickly to antibiotic therapy and cannula change. The authors conclude that outpatient IV-GnRH is safe, practical, and effective for follicular stimulation and ovulation induction in women presumed to have GnRH deficiency and in whom clomiphene therapy fails, and that less intensive monitoring is needed compared with gonadotropin ovulation induction therapy.     

Decrease in luteal gonadotropin concentration in conception cycles after in vitro fertilization/gamete intrafallopian transfer

The concentrations of the gonadotropins, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) were measured in the luteal phase of the cycle in patients undergoing ovarian hyperstimulation. In nonconception cycles, FSH and LH were increased in the late luteal phase compared with conception cycles in which both gonadotropins were suppressed. Estradiol (E2) and progesterone concentrations increased in pregnancy cycles and may be the sole cause for the decreased gonadotropin concentrations as shown by equivalent concentrations of LH and FSH in both pregnancy and nonpregnancy cycles after matching for E2 concentrations. Subjects who subsequently had twin pregnancy or a spontaneous abortion were compared with those with a successful ongoing singleton conception. There were no significant differences relative to LH and FSH between the three groups, although in twin pregnancy FSH tended to be lower at day 16 from oocyte recovery. It is concluded that suppression of LH and FSH in hyperstimulated pregnancy cycles occurs after the time of the rising human chorionic gonadotropin concentrations in plasma.     

The effects of inducing a follicular phase gonadotropin secretory pattern in normal women during the luteal phase

It has been hypothesized that the slowing of the luteinizing hormone (LH) pulse frequency in the luteal phase may be necessary for the demise of the corpus luteum, the intercycle rise in baseline follicle-stimulating hormone (FSH), or ovarian follicular development in the subsequent cycle. For assessment of the physiologic role of the luteal phase LH pulse pattern, this pattern was converted to a follicular pattern in six normal women who used exogenous gonadotropin-releasing hormone administered with a portable pump (dose 50 to 100 ng/kg subcutaneously every 90 minutes beginning in the early luteal [n = 3] and midluteal [n = 3] cycle phases). There was no significant difference between the treated and the subsequent cycle for luteal progesterone production [186.3 versus 159.0 (ng/ml) day], preovulatory follicular size (23.1 versus 22.5 mm), estradiol levels, luteal phase length (15.6 versus 14.3 days), and daily gonadotropin concentrations including the intercycle FSH rise (160.5 versus 139.1 ng/ml). A follicular phase gonadotropin pulse pattern (increased frequency, decreased amplitude) in the luteal phase had no discernible effects on the corpus luteum or on follicular development in the subsequent cycle.     

Pulsatile gonadotropin output in menstrual dysfunction.

Patterns of gonadotorpin output were studied in normal individuals and in patients with menstrual dysfunction by radioimmunoassay measurement of LH and FSH output in samples taken every 20 minutes for 6-8 hours, and following administration of synthetic luteinizing hormone releasing hormone (LRH). Follicular phase LH pulses occurred every 1-2 hours, whereas those in the luteal phase occurred less frequently and with higher amplitude. FSH output was irregular, and had no correlation with LH dynamics. In anorixia nervosa, pulsatile LH activity was minimal, and the response to LRH variable, correlating somewhat with the clinical status of the patient. Pulsatile LH activity was observed in patients with postpill and postpartum amenorrhea, and also in one individual with a probable prolactin-producing pituitary tumor. Patients with polycystic ovarian disease had obvious LH pulsatile activity, with a greater amplitude and frequency than seen in the luteal phase, and a decrease in percentage increment, suggesting some difference in the hypothalamic-pituitary control mechanisms under these conditions. The character and pattern of the LH pulsatile activity does vary with different forms of menstrual dysfunction and may be predictive of the LRH response when considered in relation to the LH baseline values. Pulsatile LH activity, analyzed in conjunction with response patterns following LRH stimulation, may reflect the degree of hypothalamic dysfunction.     

Response of gonadotropins to pituitary stimulation with luteinizing hormone releasing hormone is a more specific than sensitive parameter for the polycystic ovary syndrome.

Gonadotropin response to exogenous luteinizing hormone-releasing hormone (LHRH) was studied in two groups of patients with the polycystic ovary syndrome (PCOS). Group I (n = 44) was diagnosed as 'overt PCOS' based on clinical and endocrine abnormalities, and the typical ultrasonic picture of multicystic changes in an increased amount of ovarian stroma. Group II patients (n = 34), with similar clinical and hormonal changes, were classified as 'borderline PCOS' because endosonography of the ovaries was not conclusive. Serum gonadotropins were followed 15, 30, 45 and 60 min after administration of 100 micrograms LHRH intravenously. Plasma LH and the peak ratio of luteinizing hormone to follicle stimulating hormone (LH/FSH peak) after LHRH were significantly higher in Group I and II patients (p less than 0.001) than in controls (n = 11). There was a significant positive correlation between LH (r = 0.73 and 0.68, p less than 0.05) and LH/FSH ratio peaks (r = 0.61 and 0.68, p less than 0.05) after LHRH, and the basal values in each group. However, hyperreactivity of LH and the LH/FSH ratio after LHRH (defined as values exceeding the 95th percentile of control values) was only present in Group I in 38.6 and 56.8%, and in Group II in 47.1 and 73.5% of patients. It is concluded that: exaggerated LH release after LHRH is a typical yet not unique feature of PCOS and its sensitivity is inferior to its specificity; a higher rate for sensitivity is achieved when the LH/FSH ratio after LHRH (instead of LH release alone) is used; and that hyperreactivity of LH after LHRH is neither correlated with the plasma concentrations of total testosterone, free plasma testosterone or androstenedione, nor with the ultrasonic picture of the ovaries as significantly higher (p less than 0.05) LH and LH/FSH ratio peaks were found in borderline PCOS patients. While the heterogeneity of gonadotropin response to LHRH clearly limits its routine diagnostic use, the FSH and LH response is useful in patients with inconsistent clinical and ultrasonic features suggestive of PCOS.     

Plasma hormone profile in anovulation

Daily plasma hormones, including luteinizing hormone (LH), follicle-stimulating hormone (FSH), estrone (E1), estradiol (E2), progesterone, androstenedione, and testosterone (T), were measured in 16 anovulatory patients for a span of 3 to 4 weeks. The clinical diagnoses in this group of patients included the following: anovulation-eumenorrhea (n = 5), anovulation-polymenorrhea (n = 1), anovulation-oligomenorrhea (n = 3), congenital adrenal hyperplasia (n = 1), polycystic ovarian disease (n = 4), severe hypothalamic amenorrhea (n = 1), and postpartum amenorrhea-galactorrhea (n = 1). Follicular activity was evident in polymenorrheic and oligomenorrheic patients, and menstruation occurred in these patients following estrogen withdrawal. No follicular maturation was noted in the group of patients with anovulation-eumenorrhea, and menstruation in these patients was considered breakthrough bleeding. Low FSH levels were observed in anovulatory patients with eumenorrhea, polymenorrhea, and oligomenorrhea. Significantly high LH values were noted in both classic and non-classic polycystic ovarian disease. Extremely low E1 and E2 levels were found in patients with severe hypothalamic amenorrhea and postpartum amenorrhea-galactorrhea. Slightly elevated progesterone levels were observed in polymenorrheic and oligomenorrheic patients prior to menstruation; this was frequently associated with an LH surge or elevation. Elevated T levels were consistently associated with hirsutism but not with obesity.     

Luteinizing hormone-releasing hormone (LH-RH) as a diagnostic and research tool in gynecologic endocrinology

A study is reported on the effects of 150 mcg. of luteinizing hormone-releasing hormone (LH-RH), administered iv to 48 women with 5 types of secondary oligoamenorrhea, on the serum follicle-stimulating hormone (FSH) and luteinizing hormone (LH) Levels. At Time 0, patients with pituitary disease showed a markedly diminished LH response and patients with polycystic ovarian disease with enlarged ovaries showed a brisk, elevated LH response. FSH levels in patients with pituitary disease and polycystic ovarian disease showed a negligible rise at Time 0. 9 of 10 patients with pituitary disease and 5 of 9 patients with dietary amenorrhea had a low LH response 30 minutes after LH-RH administration. FSH response 60 minutes after injection in patients with pituitary disease and polycystic ovarian disease seemed to be lowered though too much overlap prevented a complete diagnosis. The conclusion of this initial study is that through baseline determinations of FSH and LH, along with a LH-RH stimulation test, useful data are provided for determining whether amenorrhea is due to ovarian or pituitary failure. A 2nd study evaluated the effects of 150 mcg of LH-RH administered iv before and after the im administration of various dosages of estrogen and progesterone to anovulatory women. A vigorous response in pituitary gonadotropin, particularly LH, was observed with LH-RH administered only. The effect with estrogen and progesterone was diminished pituitary response in terms of LH production. It is concluded that estrogen and progesterone exert a negative feedback effect on gonadotropin secretion at the hypothalamic and pituitary levels.     

Pulsatile release of gonadotropins in athletic women

In athletic women menstrual disorders such as luteal insufficiency, oligomenorrhea and amenorrhea are often seen. It has been suggested that such disorders may be related to hypothalamic-pituitary axis insufficiency caused by physical activity. To investigate the mechanism by which the disorder is promoted, episodic gonadotropin secretion was studied in 10 athletic women (normal ovulatory, 5; short luteal, 5) and 6 non-athletic controls. In the early follicular phase of the menstrual cycle, blood samples were obtained through an indwelling venous catheter at 15-minute intervals for 4 hours. The concentrations of luteinizing hormone (LH) and follicle-stimulating hormones (FSH) were measured by radioimmunoassay. The mean LH and FSH concentrations in the athletic groups were lower than those in the control group. LH pulse frequencies in the short luteal group were 2.8 +/- 0.2 times/four hours (mean +/- standard error) and decreased compared with that of the control group (3.7 +/- 0.2 times/four hours; p less than 0.001). The LH pulse amplitudes of all three groups were similar. Pulsatile FSH secretion was also observed in all the women. Dynamism of FSH was the same as that of LH except for low pulse amplitude in the athletic groups. These data suggest that hypothalamic-pituitary axis insufficiency, especially of hypothalamic origin may be caused by athletic activity.     

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.     

Progress and therapy of stress amenorrhea.

Thirty-two patients with stress amenorrhea of less than 1 years duration were found to have withdrawal bleeding after progestin administration, normal serum follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels, and good responsiveness to LH-releasing hormone (LH-RH); ovulation was induced following the admininstration of clomiphene citrate. On the other hand, in 11 of 14 patients with stress amenorrhea of longer than 1 years duration, no bleeding followed the administration of progestin, and there were noted high serum FSH and LH levels, exaggerated release responsiveness to LH-RH, and atrophic vaginal smears and endometrium. In addition, it was difficult to induce ovulation by various treatments. The findings suggest that dysfunction in the hypothalamic cyclic (not tonic) center regulating ovulation was the originating factor in the amenorrhea in question and that ovulation should be induced at least once yearly to prevent ovarian function from declining in this type of anovulatory state existing for more than 1 year.     

Hormonal characteristics in the early luteal phase of conceptive and nonconceptive menstrual cycles

To determine whether serum hormone profiles are different in nonconceptive and conceptive menstrual cycles after ovulation and before implantation.Daily blood samples obtained during the luteal phase of nonconceptive cycles (n = 31) and conceptive cycles (n = 19) were analyzed (intersubject comparison). Samples obtained in sequential nonconceptive and conceptive cycles from five subjects (intrasubject comparisons) were analyzed to confirm results obtained with intersubject analysis. Serum luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol (E(2)), progesterone, and relaxin were measured by immunoassay. A cell-based bioassay was used to determine whether the measurement of serum immunoreactive LH is a result of cross-reaction with human chorionic gonadotropin (hCG).Intersubject analysis showed that mean serum LH levels were significantly higher in conceptive cycles on day 4 and day 5 after the FSH peak in urine, and this was confirmed by intrasubject analysis. The addition of antibodies that precipitate hCG did not affect the activity of LH receptor ligand molecules in serum samples collected during the early luteal phase of conceptive cycles, as measured by bioassay. In contrast, this LH receptor binding activity was completely removed when precipitating antibodies for LH were added. The mean levels of serum E(2) were higher in conceptive cycles after day 4 following the FSH peak in urine. The mean values of serum FSH, progesterone, and relaxin were not significantly different in nonconceptive and conceptive cycles during the same time interval.The differences in luteal phase hormones may reflect alterations in signaling in the hypothalamic-pituitary-ovarian axis that begin during the preovulatory period of nonconceptive cycles.     

Regulation of gonadotropin secretion: implications for polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) is a disorder characterized by hyperandrogenism and chronic anovulation. Although the etiology of PCOS is unknown, perturbations of gonadotropin secretion are one of the hallmarks of this disorder. In normal menstrual physiology, the monotropic rise of plasma follicle-stimulating hormone (FSH) during the luteal-follicular transition is critical for follicular development and subsequent ovulation. One of the mechanisms by which FSH is differentially synthesized involves the luteal slowing of gonadotropin-releasing hormone (GnRH) pulse frequency by ovarian steroids. In PCOS, plasma leutinizing hormone (LH) is commonly increased, FSH is typically in the lower follicular range, and LH (and by inference GnRH) pulse frequency is persistently rapid at approximately one LH pulse per hour. The etiology of the neuroendocrine abnormalities in PCOS remain unclear; however, recent studies have revealed decreased sensitivity of the GnRH pulse generator to inhibition by ovarian steroids, particularly progesterone. This abnormality is reversed by the androgen receptor antagonist flutamide, suggesting that elevated androgen levels may alter the sensitivity of the hypothalamic GnRH pulse generator to steroid inhibition and lead to enhanced LH secretion. As such, women with PCOS require higher levels of progesterone to slow the frequency of GnRH pulse secretion, resulting in inadequate FSH synthesis and persistent LH stimulation of ovarian androgens. The decreased sensitivity of the GnRH pulse generator may help to explain the genesis of PCOS during puberty. In normal early puberty, sleep-entrained increases in LH stimulate ovarian steroids, which subsequently suppress LH frequency and amplitude during the subsequent day. In hyperandrogenemic girls destined to develop PCOS, this nocturnal increase in ovarian steroids may not be adequate to suppress the GnRH pulse generator, leading to a persistently rapid LH pulse frequency, impaired FSH production, and inadequate follicular development.     

Pituitary responses to synthetic luteinizing hormone-releasing hormone in thirty-four cases of amenorrhea or oligomenorrhea associated with galactorrhea.

Pituitary responses to 100 mcg. of luteinizing hormone-releasing hormone (LH-RH) administered subcutaneously were studied in 34 cases of amenorrhea or anovulatory oligomenorrhea associated with galactorrhea. Twenty-six patients had pituitary prolactin-secreting tumors (group I); eight patients had a normal sella turcica and remission of the syndrome either spontaneously or after thyroid replacement therapy (group 2). Follicle-stimulating hormone (FSH) and luteinizing hormone (LH) responses to LH-RH were variable in each group of patients, ranging from poor to exaggerated, and no statistically significant difference could be observed between the groups. A positive correlation was found between FSH pituitary responses and basal FSH levels (r=0.50; P less than 0.01). No positive correlation was observed between either LH responses and basal LH levels or the gonadotropin responses and plasma estradiol levels, serum prolactin concentrations, duration of amenorrhea, or size of the tumor.     

The acute feedback action of exogenously administered oestrogens on the serum-gonadotropin-levels in pre- and postmenopausal women (author's transl)

The effects of estradiol benzoate (EB), ethinyl estradiol (EE), and mestranol in different dosages on serum luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels were measured by dioxane-radioimmunoassay at intervals of hours and days. All postmenopausal women studied here reacted with a pronounced suppression of both FSH and LH. The LH decline starts 4-10 hours earlier than FSH and returns - after the minumum on Days 2-3 - to the controls on Days 5-6, while the FSH levels show a longer suppression. Neither in the type of estrogen nor in the administered dose a marked qualitative difference could be observed. Only after 3 mg EE and 15 mg mestranol a prolonged inhibitory effect on FSH and LH became evident. Results in premenopausal women were quite different. In 7 women with a history of amenorrhea or anovulatory cycles 5 mg EB was given. A small decline after 24 hours was followed by a sharp rise of LH 1 day later which is comparable to the preovulatory LH peak. In the subsequent days values returned to control levels. The FSH curve did not show a similar peak. Only 1 woman ovulated and became pregnant. In another group of 11 women with normal menstrual cycles, 5 mg EB was injected at different times of the follicular, periovulatory, and luteal phases. The patterns of serum LH and FSH were comparable to the results in amenorrheic patients. In all cases an LH peak appeared on Days 2-3, which seemed to be higher in the preovulatory than in the postovulatory phase. The FSH curves remained uncharacteristic with small oscillations. The role of the physiological follicular estrogen peak for triggering the LH surge is discussed as well as the possibility of checking the response of the hypothalamic-hypophyseal system by exogenous estrogen application.     

Reference intervals for serum sex steroids and gonadotropins in regularly menstruating women.

Reference intervals for novel fluoro-immunoassays for serum luteinizing hormone (LH), follicle stimulating hormone (FSH), estradiol (E2) and progesterone (P) were established in 40 healthy regularly menstruating women. Serum samples for sex steroids, including testosterone (T), androstenedione (A) and dehydroepiandrosterone sulphate (DHEAS), as well as sex hormone binding globulin (SHBG) and gonadotropins, were collected in the early follicular and mid-luteal phases of the menstrual cycle. The need for the timing of androgen and gonadotropin samples was also determinated. Serum E2 and P were measured by radio-immuno- and time-resolved fluoro-immunoassays. Various assay methods correlated closely, but the reference intervals varied considerably from one method to another. In the early follicular phase the LH/FSH ratio only ranged between 0.2 and 1.7 (mean +/- S.D.; 0.8 +/- 0.3); the variation was greater (from 0.3 to 3.5) in the luteal phase, when the mean was also significantly higher (1.5 +/- 0.9, p = 0.0001). Similarly the mean values of T and SHBG were higher in the luteal phase, while the other androgen concentrations and calculated androgen indexes were equal, compared with the follicular phase values. Thus the timing of hormone determinations is warranted in the investigation of the gonadotropin and androgen status in normally menstruating women. Moreover, the upper limit of the LH/FSH ratio examined with new, sensitive methods is lower than that previously stated. The use of an intra-uterine contraceptive device (IUD) had no effect on hormone levels.     

Controlled ovarian hyperstimulation: a review for the non-ART patient

Controlled ovarian hyperstimulation (COH) involves the administration of oral and/or injectable medications to induce ovulation in the anovulatory infertile patient, and superovulation in the ovulatory infertile patient. The different types of medication and protocols for COH are reviewed. Oral medications such as clomiphene and letrozole should be considered in most patients initially, except in the case of hypogonadotropic amenorrhea. Pregnancy rates are higher with the injectable medications, follicle stimualtion hormone (FSH) and human menopausal gonadotrpins (hMG), than oral medications; however, injectable medications have a higher risk of multiple gestation, ovarian hyperstimulation syndrome, cost and monitoring. Strategies to enhance the responsiveness to these medications in polycystic ovarian syndrome patients including adjunctive treatment with metformin and/or dexamethasone will be discussed. Combined protocols which use oral and injectable gonadotropins may also lower risks and costs without sacrificing chances of pregnancy. Patients with hypogonadotropic amenorrhea benefit from the addition of leutinizing hormone (LH) activity such as hMG, recombinant leutinizing hormone (rLH) or low dose human chroionic gonadotropin to FSH stimulation. Ovulation and luteal phase support with progesterone is generally recommended in injectable cycles but not with oral medications.     

Gonadotropin-releasing hormone-induced changes in testosterone secretion in normal women

This study investigated the pattern of testosterone (T) secretion in spontaneous (n = 14) and gonadotropin-releasing hormone (GnRH)-treated (n = 6) menstrual cycles in normal women. In spontaneous cycles, T was found to increase progressively over the follicular phase (P less than or equal to 0.001), with the peak T value occurring on cycle day 0 (luteinizing hormone [LH] surge). The mean (+/- standard error of the mean [SEM]) T values on cycle day -14 and cycle day 0 were 35 +/- 4 and 51 +/- 4 ng/dl, respectively. GnRH was administered intravenously to six women at 1.3 to 1.7 micrograms per dose every 30 minutes in a study that assessed the ovarian effects of a rapid gonadotropin pulse frequency. In three of the women, the T levels followed a normal follicular phase pattern, whereas in the remaining three GnRH-treated women, there were marked increases in T with peak levels of 97, 123, and 81 ng/dl on day 0. The GnRH-treated subgroup with increased T levels had significantly increased follicular levels of LH, follicle-stimulating hormone (FSH), LH-bio and number of preovulatory ovarian follicles. This study demonstrated that increased levels of LH, FSH, and LH/FSH are capable of acutely increasing the secretion of ovarian androgens.