Lower Luteinizing Hormone Levels Research Articles

Gonadal dysfunction in patients treated for metastatic germ-cell tumors.

The effects of chemotherapy on endocrine function were assessed in 22 previously treated patients with germ-cell tumors and compared with the endocrine function of six previously untreated patients. Baseline and stimulated serum levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone, thyroid-stimulating hormone (TSH), prolactin, and thyroxine (T4) were obtained. Baseline LH levels were elevated in both groups of patients, whereas basal FSH levels were significantly elevated only in treated patients (P less than .001). Following gonadotropin-releasing hormone (GnRH), levels of LH (P = .051) and FSH (P = .003) were greater in treated patients than in untreated control patients. No abnormalities of thyroid function or prolactin responsiveness were observed. Patients younger than 25 years of age at the time of treatment had lower serum levels of LH and FSH following chemotherapy than patients older than 25. Evidence for partial recovery of gonadal function was present with patients treated more than 18 months before study having lower levels of LH and FSH than those patients studied less than 18 months after treatment. These data demonstrate that frequent gonadal dysfunction exists in untreated patients with germ-cell tumors and that chemotherapy induces additional injury to both Leydig cells and the germinal epithelium. Further studies with long-term follow-up are necessary to define the pattern of gonadal recovery and to assess the potential sequelae of endogenous gonadotropin hypersecretion.

Hot Flushes in a 76-Year-Old Man

To the Editor.— In the QUESTIONS AND ANSWERS section ofThe Journal, 1 there was a question concerning flushing in a 76-year-old man. The two replies failed to mention a low testosterone level as a cause of flushing. Report of a Case.— In November 1976, I saw a 48-year-old man who had sweating and hot flushes. He was afebrile and had a positive tuberculin test result but a normal chest roentgenogram, and he was treated with isoniazid for a year. Because his flushes continued, in December 1977 a serum testosterone value was obtained, which was 40 μg/dL (normal range, 400 to 1,000 μg/dL). He also had a low luteinizing hormone level, 3.5 mIU/mL (normal range, 4 to 22 mIU/mL), a normal prolactin value, and a normal cortisol level. Thyroid function study values were low; the free thyroxine index was 13 (normal range, 18 to 46). A computed tomographic scan of

Influence of Day Length and Endocrine Status on Luteinizing Hormone Secretion in Intact and Ovariectomized Adult Ferrets1

The purpose of this study was to examine the pituitary-ovarian relationship of both estrous and anestrous female ferrets. The endocrine status of the animals was induced by manipulating photoperiod: females in estrus were housed in long days (16L:8D); females in anestrus were housed in short days (8L:16D). For studies of intact animals in both photoperiods, plasma luteinizing hormone (LH) levels were quantified in blood samples collected from adult ferrets at 5-min intervals over a 24-h period. Similar groups of females (estrous and anestrous) were ovariectomized (while remaining in their assigned photoperiods) and blood samples were collected at 5-min intervals for 4-h periods on Days 1, 2, 4, 10, 17, and 35 after ovariectomy. Intact, estrous females exhibited continuously low or undetectable levels of LH with no evidence of episodic secretion. Ovariectomy of these estrous animals resulted in rapid onset (within 24 h) of episodic LH secretion, with pulses occurring in excess of 1 pulse/h. No substantial further change in frequency or amplitude of pulses occurred in these females from 1 to 35 days postovariectomy. In contrast, intact anestrous ferrets exhibited clear episodic LH secretion at a frequency of about 0.4 pulses/h. Removal of ovaries from these females caused no change in LH secretion for 24-48 h, after which LH pulses gradually increased in frequency. By 18 days after ovariectomy, LH patterns were indistinguishable among ovariectomized females in long and short days. These studies suggest a major site of ovarian negative feedback on LH secretion during anestrus is the hypothalamus, whereas the site of the ovarian feedback in estrous females is not yet evident.

Negative Feedback Regulation of Gonadotropin Secretion by Androgens in Fetal Rhesus Macaques1

Previously we described sex differences in circulating gonadotropin concentrations (greater in females) in fetal rhesus macaques, and demonstrated that these sex differences relate, at least in part, to the negative feedback actions of testicular secretions. A fully functional gonadal-hypothalamic-pituitary feedback relationship is present as early as Day 100 of gestation in fetal males because castration at this time results in a dramatic increase (greater than 10-fold) in fetal luteinizing hormone (LH) concentrations. Although short-term (6-h) treatment of fetuses with testosterone (T) 3 wk after gonadectomy (GX) does not lower LH levels in males, it is completely effective in females. These data suggest that either T is not the primary testicular factor responsible for feedback suppression of LH in fetal males, or the hypothalamic-pituitary axis becomes insensitive to T after GX. To determine if immediate treatment with T after GX is effective in maintaining LH levels, we gonadectomized five fetal rhesus males on Days 98-104 of gestation and immediately implanted crystalline-T-containing intraabdominal Silastic capsules. An additional five fetuses were treated with the nonaromatizable androgen dihydrotestosterone (DHT). Umbilical arterial samples for hormone analysis were obtained prior to GX and again approximately 3 wk later. Serum from control males (n = 11) castrated in utero on Day 100 of gestation contained significantly greater concentrations of LH and follicle-stimulating hormone (FSH) 3 wk after the operation than before GX. Five sham-operated male fetuses did not have elevated levels of either LH or FSH in their serum on Day 120 of gestation.(ABSTRACT TRUNCATED AT 250 WORDS)

Changes in LH and prolactin levels in diabetic male rats and the role of the opiate system in the control of their secretion

Diabetic male rat has low serum levels of luteinizing hormone (LH) and testosterone (T), which are accompanied by atrophy of the testes and accessory glands. The present study investigated changes in the serum levels of LH, prolactin (PRL) and glucose, following diabetes induction by streptozotocin. In addition, involvement of the opiate system in the control of LH and PRL secretion was evaluated. There was no difference in PRL levels between diabetic and control animals, except at 8 hours after streptozotocin injection. In contrast, the diabetic animals had consistently lower levels of LH, starting on the second day of diabetes. Blockade of the opiate system by naltrexone caused a sharp increase of LH levels in normoglycemic rats, while only a gradual decrease was observed in hyperglycemic animals. PRL secretion was inhibited by naltrexone, both in diabetic and control groups. It is concluded that, unlike normoglycemic rats, inhibition of LH secretion in diabetes is not under the control of the opiate system, probably as a result of T deficiency. In contrast, PRL secretion in diabetic rats, as in the control group, is under the influence of endogenous opiates.

CIRCANNUAL CHANGES IN SERUM LEVELS OF PITUITARY HORMONES AND TESTOSTERONE AND IN TESTIS SIZE OF SEXUALLY ACTIVE AND INACTIVE ADULT RAMS

The influence of the social environment of adult rams on testicular function and the secretion of pituitary hormones was investigated between May 1978 and October 1979. Twelve rams, 3–6 yr of age, were penned in three groups of four, either as a sexually inactive all-male group or as sexually active groups adjacent to or together with ovariectomized ewes that were hormonally induced into estrus every 10 days. At approximately monthly intervals measurements of testis size were recorded and rams were bled by venepuncture from the jugular vein at 20-min intervals for 8 h (0900–1700 h). Sera were assayed for luteinizing hormone (LH), follicle stimulating hormone (FSH), prolactin (PRL) and testosterone. Since seasonal changes in testicular and endocrine characteristics for the sexually active groups were similar, data for these groups were combined. Differences in the circannual testicular rhythm were not observed between ram groups until the onset of the second breeding season; at this time (August 1979), sexually active rams had significantly (P < 0.05) higher scrotal circumference measurements (36.0 ± 0.9 vs. 32.2 ± 1.0 cm) and circulating testosterone levels (10.7 ± 1.6 vs. 6.7 ± 1.5 ng/mL), and significantly (P < 0.05) lower LH levels (0.75 ± 0.10 vs. 2.04 ± 0.40 ng/mL) than sexually inactive rams. The increase in rate of testicular redevelopment for sexually active rams during late summer was not preceded by significantly (P > 0.05) higher seasonal elevations in circulating LH and FSH levels, although PRL levels in May through July were only 50% of those observed for the sexually inactive rams. Sexually active rams also exhibited significant (P < 0.01) increases in LH and testosterone secretion in the nonbreeding season when ewes were sexually receptive. Ejaculation frequency during a 4-h test period at the conclusion of the study was similar for both groups of rams. Data indicate that long-term exposure of adult rams to estrual ewes results in an increase in rate of testicular redevelopment during the summer in preparation for the fall breeding season. Key words: Circannual changes, pituitary hormones, testosterone, testis, mating, ram

Hypothalamic gonadotropin-releasing hormone and pituitary luteinizing hormone contents in the male vole (Microtus agrestis) in the field during the breeding and nonbreeding seasons

Pituitary luteinizing hormone (LH) and hypothalamic gonadotropin-releasing hormone (GnRH) contents were measured in male voles trapped in the field over a period of 5 years. Pituitary LH contents were positively correlated with testicular and seminal vesicle weights but hypothalamic GnRH contents showed no correlation with pituitary LH contents or organ weights. Pituitary LH contents and testicular and seminal vesicle weights increased between January to April, reached peak values during May to July, and fell from August to December. Hypothalamic GnRH contents were high for most of the year with low values during December and January. During July, August, and September two populations of males were studied; a group with large active testes and high pituitary LH levels and a group with small testes and low pituitary LH levels. With the exception of the group in July of animals with small testes, all males, both sexually active and inhibited, had high hypothalamic GnRH levels.

Importance of retinal photoreceptors to the photoperiodic control of seasonal breeding in the ewe.

Two experiments were performed to determine whether the eyes are necessary for photoperiodic control of reproduction in ewes. In the first, intact and estradiol-treated ovariectomized (OVX + E) ewes were housed in each of 2 photoperiod-controlled rooms with a vasectomized ram and subjected to 90-day alternations between long and short days. Prior to blinding, long days initiated anestrus in intact ewes and a suppression of serum luteinizing hormone (LH) levels in OVX + E ewes; short days caused onset of estrous cycles and an increase in LH levels in the intact and OVX + E ewes, respectively. After 1.5 years of such photoperiodic control, all ewes were blinded by bilateral orbital enucleation. Photoperiodic control was lost following blinding, but circannual alternations between cyclicity and anestrus or high and low LH levels, were maintained in most ewes for the remaining 2.5 years of the study. In one group of OVX + E ewes, serum LH levels remained synchronized to the 90-day shifts in photoperiod for about 1 year after blinding. Once the sighted ram was removed from the room, however, the 90-day rhythm in LH disappeared and a circannual pattern of LH became evident, suggesting that blind ewes may receive photoperiodic information from a sighted ram. This possibility was supported by the results of the second experiment in which 12 additional OVX + E ewes were blinded and exposed to 90 long days and 90 short days in the absence of a sighted ram. In these ewes, serum LH levels were not controlled by the changes in photoperiod. These results are consistent with the following conclusions: 1) the eyes are necessary for perception of photoperiod in the ewe and 2) ewes have an endogenous circannual rhythm of reproduction and/or they can be controlled by other environmental signals in the absence of photoperiodic input. Further, the results lead to the hypothesis that blind ewes can receive photoperiodic information indirectly from a sighted ram.

Endocrine Responses of White-Crowned Sparrows to Environmental Stress

Field and laboratory investigations were conducted to assess the effects of selected stressors on White-crowned Sparrows (Zonotrichia leucophrys gambelii and Z. l. pugetensis). Within a few minutes after capture during the non-breeding winter phase, the birds' plasma corticosterone increased, whereas their already low levels of luteinizing hormone (LH) and dihydrotesterone (DHT) declined further. In contrast, in the summer, or breeding phase, corticosterone levels increased much more slowly (sometimes not at all in females) during the first hour after capture. Plasma levels of LH in breeding birds were unaffected by capture and handling, as were levels of DHT in males and estrogen in females. In some cases, however, circulating levels of testosterone declined in males. In photostimulated, caged, male Z. l. gambelii circulating levels of corticosterone, LH, and DHT appeared to be unaffected by ambient temperatures between 5° and 32°C, but the level of testosterone was significantly depressed at 32°C. Capture, transport for 250 km, and subsequent caging of male and female Z. l. gambelii in autumn and winter within 24 h increased plasma corticosterone, and decreased LH and DHT. As the birds acclimated to captivity, a decrease in levels of corticosterone was followed by transient elevations of LH and DHT after which concentrations of these hormones stabilized at capture levels. Males transferred from outdoor aviaries and held one, two, or three per cage on short days also developed elevated concentrations of corticosterone and depressed levels of LH and DHT. Corticosterone decreased within two weeks in birds held one or two per cage, and within three weeks in those housed three per cage. As corticosterone levels decreased, transient increases occurred in LH and DHT, with the highest levels in birds held three per cage.

Depressed prolactin levels in diabetic women with anovulation.

The circulating levels of prolactin (PRL), luteinizing hormone (LH), follicle stimulating hormone (FSH) and estradiol-17 beta were determined by radioimmunoassay in 76 normal healthy women in the follicular phase of the menstrual cycle, 54 consecutive anovulatory non-diabetic women and 20 consecutive diabetic women with anovulation. An elevated plasma PRL concentration was found in 1/20 (5%) of the diabetic women and in 17/54 (32%) of the non-diabetic anovulatory women (p less than 0.05). Plasma concentrations of estradiol-17 beta and gonadotropins in diabetics did not differ (p greater than 0.05) from those found in non-diabetic women with anovulation. Diabetic women with secondary amenorrhea had significantly (p less than 0.05) lower plasma concentrations of PRL and estradiol-17 beta than non-diabetic women with amenorrhea and normal controls. Furthermore, this group of diabetic women had lower median plasma LH concentrations than the non-diabetics with secondary amenorrhea and normal controls, but this difference was not significant (p greater than 0.05). These data indicate that diabetic patients with anovulation have hypothalamic and/or pituitary defects. Furthermore, the low prolactin and LH levels despite a low estradiol-17 beta concentration may suggest an increased hypothalamic dopamine activity in patients with diabetes mellitus and secondary amenorrhea.

Postovulatory steroidogenesis after PMS-induced ovulation in immature female rats.

Thirty-day-old rats given a single subcutaneous injection of 5 IU pregnant mare serum gonadotropin (PMS) at 0900 h ovulated on the morning of day 33 (= estrus). However, the second ovulation did not occur until 9.4 days later. To determine the mechanism responsible for the delay in the second ovulation, in vivo and in vitro determinations of steroid and peptide hormones were compared between PMS-primed immature rats and adult cyclic rats. In PMS-primed rats, the corpora lutea (CL) produced progesterone for 2 days longer (until day 36) than the CL of the adult rat. Serum levels of 20 alpha-dihydroprogesterone, testosterone, and estradiol in PMS-primed rats were significantly lower than the corresponding values in adult rats. Serum LH was consistently lower in the PMS-primed rats. An increase in serum FSH occurred on days 36-37, which may be responsible for maturation of the follicles destined to ovulate at the second ovulation. On day 37, the nonluteal ovary of the PMS-primed rats also began to produce in vitro appreciable amounts of testosterone and estradiol. These findings suggest that the greater levels of prolactin and/or low levels of luteinizing hormone during estrus in PMS-primed rats may be responsible for the prolonged secretion of progesterone by the CL. This in turn inhibits follicular maturation, indirectly by lowering serum LH, which is reflected in reduced ability of the follicles in vitro to produce testosterone and estradiol until the CL regress.

The relationship of plasma gonadotropins and androgen concentrations to body growth in boys.

Abstract. Plasma concentrations of luteinizing hormone (LH), follicle-stimulating hormone (FSH), 17 alpha-hydroxyprogesterone (17α-OPH), androstenedione (Δ4) and testosterone (T) were measured in 543 healthy boys aged 6.0 to 15.9 years (with weight and height between the 3rd and 97th percentile for Mexican standards) as a function of chronologic age (CA), weight, height, surface area (SA) and calculated lean body mass (LBM) and total body fat (TBF). The earliest hormonal event was a clear rise in plasma 17α-OHP, either prior or simultaneously to at steady increase in plasma FSH, far ahead of any sign of puberty. These changes were closely followed by a continuous rise in plasma Δ4. Thereafter, there was a prolonged period of low but progressively increasing plasma FSH levels in the face of constantly low LH levels. However, a brisk rise in plasma LH and FSH occurred at a mean weight of 35.4 kg, at a height of 144.5 cm and when LBM was 32.0 kg. Simultaneously, plasma 17α-OHP began to fall, Δ4 reached a plateau and soon after, a marked rise in plasma T was documented. When plasma LH and FSH concentrations were plotted against CA, weight, height, SA and LBM a significant quadratic equation was disclosed in each case. Both gonadotrophins did not correlate with TBF. Multiple variance analysis demonstrated that LBM and SA had the most marked effect on LH, while LBM was the most important variable affecting plasma FSH concentrations. The present data suggest the association between a "critical level" of body composition and the major hormonal events in boys, regardless of a cause-effect relationship. A critical level of LBM (20–23 kg) and not of TBF was attained at time of the initial hormonal changes, as well as at the time of the major changes in plasma gonadotrophins (32–35 kg).

Prolactin and Sexual Function

To the Editor.— Regarding the article by Spark and co-workers (243:750, 1980) about hormonal evaluation in sexually impotent men, we would like to emphasize some points, particularly about the role of prolactin on sexual function. In the years 1975 to 1979, we saw 134 patients complaining of sexual disturbances (ie, impotence or ejaculatio precox) of nonorganic origin who were referred to our endocrine unit. All patients had serum luteinizing hormone (LH), follicle-stimulating hormone (FSH), prolactin (PRL), testosterone, and 17 β-estradiol routinely determined by specific radioimmunoassay methods (Biodata Serono Kits). In our series mean (±SE) serum LH and FSH concentrations were not significantly different from those obtained in normal subjects (LH, 11.5± 0.6 vs 11.2±1.4 mIU/mL; FSH, 8.1±0.6 vs 6.5±0.4 mIU/mL); abnormally high or low LH and FSH levels were recorded in only 5% and 7% of cases, respectively. Though the mean serum PRL concentration in basal conditions did not significantly

Effects of arginine vasotocin, oxytocin, and arginine vasopressin on steroid-induced surges of luteinizing hormone and prolactin in ovariectomized rats.

Abstract. Several studies have indicated that arginine vasotocin (AVT), a nonapeptide closely related to vasopressin (ADH) and oxytocin (OT), may act as a pineal antigonadotrophic factor. The present studies were designed to investigate the effects of AVT on the luteinizing hormone (LH) and prolactin (Prl) release induced by sequential steroid priming of ovariectomized (OVX). rats. Sprague-Dawley rats were used 6–8 weeks post-OVX. After implantation of an intra-atrial bleeding catheter, animals were primed with 5 μg of oestradiol benzoate (EB) at 08.00 h on the next morning. Forty-eight hours later 1.5 mg of progesterone (P) was injected and animals were divided into groups which received either saline, AVT (1 of 4 doses), ADH, or OT. The saline or peptides were infused via the intra-atrial catheter at 10.00, 11.00, 12.00, and 13.00 h. Hourly blood sampling was performed at 11.00–18.00 h, and at 21.00 h. The 11.00, 12.00, and 13.00 h samples were taken 10 min after saline or peptide infusion. LH and Prl responses to the peptide infusions could be divided into pre-surge and surge effects. AVT caused a slight, but significant elevation of the normally low levels of LH and Prl which occurred before the onset of their surges. Only the highest dose of AVT (1.0 μg) blocked the LH surge. ADH, however, was capable of stimulating LH and Prl release during the pre-surge period and of inhibiting the LH surge. AVT at a dose of 0.5 or 1.0 μg specifically blocked the onset of the Prl surge, causing Prl to drop to its lowest level at 14.00 h - the time at which Prl levels were maximal in saline-treated animals. After this initial inhibition, however, Prl levels rebounded to show a delayed surge. OT infusion, on the other hand, caused a significant augmentation of the Prl surge. These data indicate that AVT may specifically block the onset of the Prl surge seen after sequential steroid priming of OVX rats, while OT may facilitate the Prl surge.

Neonatal ablation of the suprachiasmatic nucleus. Effects on the development of the pituitary-gonadal axis in the female rat.

Ablation of the suprachiasmatic nucleus (SCN) at 2 days of age, prior to the formation of the retinohypothalamic projection, produces a permanent state of constant vaginal estrus in the postpubertal female rat. Although such lesions do not alter the onset of puberty in sighted rats, they do compensate for the delay in vaginal opening induced by neonatal binding. The ovaries of sighted and blinded SCN-lesion rats are small and polyfollicular and the pituitaries of blinded SCN-lesion rats are abnormally large. Sampling of plasma in the morning and afternoon for up to 12 consecutive days in sighted SCN-lesion rats reveals continuously low luteinizing hormone levels. This constellation of endocrine alterations does not correlate with damage to any structures outside the SCN. Since the organization of the rodent estrous cycle is circadian, these results emphasize further the importance of the SCN in circadian rhythm generation. The necessity of an intact SCN for the development of normal, cyclic reproductive function implies that sparing or recovery of function does not occur.

Hormonal Factors Related to the Incidence of Testicular Tumors in Male Pseudohermaphrodite Rats

Pieces of testicular tumor from male pseudohermaphrodite (tfm) rats were transplanted between the skin and body wall musculature of 4-day-old female, male, and tfm hosts and to the anterior chambers of the eyes of gonadectomized and intact adult tfm, female, and male hosts. These transplants grew in all hosts except normal males. To determine whether these tumors were hormone-dependent, the levels of circulating gonadotropins were measured in all host types to ascertain which were low in the males and high in all of the others. Prolactin, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) levels were measured in intact and castrated normal and tfm rats. Normal males had low levels of prolactin, estrogen, LH, and FSH; however, transplants grew well in other hosts with low titers of these hormones. Except for normal males, all hosts had high serum levels of LH. Thus, testicular tumors in tfm rats appear to be LH-dependent.

A Syndrome of Functional Hypogonadotropic Hypogonadism and Sterility in a Male with Elevated Serum Estradiol

A 36-year-old male complaining of impotence was examined. He was a genotypic male. Phenotypically, he exhibited signs of long-standing estrogen excess, such as feminine body build, gynecomastia, and varicose veins. His testes were soft and borderline small, and his prostate was small and soft. However, he had a normal-sized penis, normal male hair distribution, normal sense of smell, and normal intelligence. The laboratory data were compatible with mild hypogonadotropic hypogonadism. Serum estradiol (E2) levels were consistently elevated. The patient had azoospermia and a decreased semen volume. Inappropriately low levels of luteinizing hormone and follicle-stimulating hormone responded normally to gonadotropin-releasing hormone and clomiphene citrate. Levels of both testosterone (T) and E2 increased dramatically after prolonged clomiphene medication and in response to human chorionic gonadotropin. There was no change in either T or E2 levels in response to manipulations of the pituitary-adrenal axis. It is concluded that the elevated E2 level was responsible for suppression of gonadotropins which, in turn, caused mild hypogonadism and sterility in this patient. According to the stimulation tests, the source of the elevated E2 levels was testicular.

A Study of the Endocrine Manifestations of Hepatic Cirrhosis

The clinical features and hormonal abnormalities were surveyed in 117 men with cirrhosis of the liver. Compared with healthy men of similar ages, the patients had significantly lower metabolic clearance rates, plasma production rates and total and free levels of testosterone, reduced testosterone responses to human chorionic gonadotrophin stimulation, higher oestradiol, luteinizing hormone and follicle stimulating hormone levels and higher binding capacities of sex steroid binding globulin. The peripheral conversion of testosterone to oestradiol was also found to be significantly increased. However, the metabolic clearance and plasma production rates of oestradiol were not significantly different from those of healthy men. Patients who were severely ill with liver failure and one with haemochromatosis had low levels of luteinizing hormone and follicle stimulating hormone and sub-normal responses to clomiphene and luteinizing hormone-releasing hormone. Higher plasma oestradiol levels were found in patients with gynaecomastia and spider naevi than in those without these signs. However, the clinical features of androgen deficiency—that is, testicular atrophy, impotence and loss of secondary sex hair—were only poorly related to the low testosterone levels, and production rates and longtitudinal studies indicated that the hormonal levels, endocrine features and severity of the liver disease could change independently. It is concluded that the clearance of oestradiol from plasma is not limited by liver disease in all patients, and that reduced degradation of oestrogens is not the initial event in the sequence leading to the hormonal abnormalities of cirrhosis. While gonadotrophin deficiency occurs with liver failure and in some patients with haemo-chromatosis, the more usual findings are of elevated gonadotrophin levels and a poor Leydig cell response to chorionic gonadotrophin. These suggest that the hypo-gonadism is primary in most patients with cirrhosis. The causes of the high oestradiol levels were not discovered. Increased peripheral conversion of precursors to oestradiol or increased testicular secretion of oestradiol are possibilities. The high binding capacities of sex steroid binding globulin were not significantly correlated with either the low testosterone or high oestradiol level and the cause of this abnormality remains uncertain. The low metabolic clearance rates of testosterone appeared to result from the increased plasma protein binding of testosterone. The discrepancies in the expected relationships between the hormone and clinical changes suggest that factors other than those studied are also involved in the genesis of the endocrine features of hepatic cirrhosis.

Contraception and inhibition of ovulation by minipump infusion of the luteinizing hormone releasing hormone, active analogs and antagonists

The effects of luteinizing hormone-releasing hormone (LH-RH) and its active analogs and antagonists on ovulation and serum luteinizing hormone (LH) levels were studied in male and female rats. When the antagonist (D-Phe(2)Pro(3)D-Trp(6))-LH-RH was infused sc at the rate of 375 mcg/day for 4 days by a subcutaneous osmosis-driven minipump ovulation was inhibited and serum levels of LH were decreased in castrated male rats. (D-Phe(2)Leu(3)D-Trp(6))-LH-RH was not as effective in suppressing ovulation but did lower LH levels in castrated animals. Infusion of 375 mcg/day LH-RH for 4 days in combination with ca. 6 mcg/day for 4 days of the highly active analog (D-Ala(6)des-Gly(10)-LH-RH completely abolished the uterine implantation sites of mated rats. The LH-RH antagonists were ineffective. It appears that the mechanisms of action of LH-RH and its superactive analogs which cause postcoital contraception and the mechanisms of antagonists of LH-RH which prevent ovulation are different.

The effects of clomiphene citrate on the hypothalamic–pituitary–gonadal axis in anorexia nervosa

Serum luteinizing hormone (LH) responses to a course of clomiphene citrate were studied in eleven patients with anorexia nervosa at different stages of the illness. In malnourished patients basal levels of LH were invariably low. With the resumption of a normal weight a small but definite rise in LH levels was observed but this spontaneous response to weight gain was variable in that many patients continued to exhibit abnormally low LH levels. The response to clomiphene in terms of a rise in basal LH levels after administration of the drug, followed by a second peak of LH and subsequent menstrual bleeding, was clearly dependent in part on the patient's nutritional state. In the malnourished state the response to clomiphene was usually either absent or incomplete. After the resumption of a more normal weight, the patients invariably showed an initial rise in LH after the clomiphene, but the second LH peak and subsequent menstruation were frequently not demonstrated. Six patients maintained a normal body weight for at least six months after a course of clomiphene, but only three of them resumed cyclical menstrual bleeding. It was concluded that factors additional to the nutritional state contribute to the prolonged amenorrhoea in anorexia nervosa and that clomiphene appears to have only a limited role in the treatment and management of patients with the disorder. Some aspects of current knowledge of the endocrine mechanisms that regulate normal menstruation and of the mode of action of clomiphene are outlined. The results of the present study are discussed against this background in an attempt to elucidate further the hypothalamic disorder underlying the amenorrhoea in anorexia nervosa.