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Ovulation induction with pulsatile gonadotropin-releasing hormone: a study of the subcutaneous route of administration.

The efficacy of ovulation induction with the use of intermittent gonadotropin-releasing hormone (GnRH) therapy was examined in seven infertile women with hypothalamic amenorrhea. GnRH was administered every 90 minutes via the subcutaneous route in doses ranging from 50 to 300 ng/kg. Analysis of the induced gonadotropin pulse pattern revealed normal to modestly increased luteinizing hormone secretory parameters (e.g., pulse amplitude) in six of the seven patients. Six of seven women and 15 of 16 treatment cycles (94%) were ovulatory. The conception rate was 43% per woman and 19% per cycle. However, detailed hormonal analysis of 13 treatment cycles revealed that only 1 cycle was entirely normal in terms of duration and/or steroid secretion.

Adult↗

The significance of galactorrhea in patients with normal menses, oligomenorrhea, and secondary amenorrhea.

Thyroid-stimulating hormone and prolactin (PRL) were measured in a group of 149 women with galactorrhea. Three of these patients were found to have primary hypothyroidism. In the remaining 146 patients, the PRL assay was correlated with the menstrual history and the results of hypocycloidal polytomography. Sixty-two per cent of these patients had hyperprolactinemia and 35 per cent had abnormal tomograms. Nine patients with abnormal x-rays had normal prolactin levels. None of the patients with normal menses and normal PRL was found to have an abnormal x-ray. Fourteen of the 15 patients with PRL levels greater than 200 ng. per milliliter had abnormal tomograms. Almost 70 per cent of patients with secondary amenorrhea and low estrogen status had abnormal x-rays. In patients with oligomenorrhea and secondary amenorrhea with normal estrogen status, it was not possible to differentiate between patients with normal or abnormal tomograms based on the level of serum PRL. Polytomography remains the single most important diagnostic test in establishing the presence of a pituitary tumor.

Adolescent↗

Serum luteinizing hormone profile during the menstrual cycle in polycystic ovarian syndrome.

Thirty-three patients with PCO were studied, focusing on the serum LH profile appearing during their menstrual cycles. The elevated LH level declined gradually after ovulation to the normal or near-normal range at the end of the luteal phase and the early follicular phase. The once declined LH level gradually elevated again with the increasing days from the beginning of menstrual flow and remained at a high level until the next ovulation. The LH response to LH-RH increased with the elevating basal LH level. These results may suggest that the timing of hormonal analysis is important for correct diagnosis of PCO.

Adolescent↗

Comparisons of the potential utility of LHRH agonists and antagonists for fertility control.

Prospects for the use of LHRH analogs for human fertility control have been reviewed with particular reference to two highly potent representatives. Nafarelin acetate, the LHRH agonist, has a potency about 200 X that of LHRH and is consistently effective in suppressing gonadal function in females through a desensitization of LHRH receptors in the pituitary. Such agents show promise as ovulation inhibitors for women although concern has been expressed over the dangers of unopposed estrogen or alternatively hypoestrogenemia. Although early studies indicated luteolysis in women and interceptive action in baboons it is now clear that the LHRH agonists will not be useful clinically to terminate pregnancy. Wide species differences in the male response to LHRH agonists exist. Unfortunately azoospermia has not been achieved in men. The LHRH antagonists, typified by [N-Ac-D-Nal(2)1, D-pCl-Phe2, D-Trp3, D-hArg(Et2)6, D-Ala10]LHRH, require high doses to competitively inhibit responses to endogenous LHRH. Their advantages include a rapid induction of the hypogonadal state with apparently little species or sexual variation in response. Based on animal studies, preferable utility of the antagonists would lie in male contraception and pregnancy interception.

Abortion, Induced↗

Hyposexuality and epilepsy: a community survey of hormonal and behavioural changes in male epileptics.

A survey of five group practices in South London identified 60 male patients currently undergoing treatment for epilepsy. Fifty-four agreed to participate in a detailed enquiry into aspects of their sexual activity and behaviour. Anterior pituitary and sex-hormone levels were measured. The epileptic patients were characterized by low levels of sexual activity and interest. Temporal-lobe and non-temporal-lobe epileptics were indistinguishable in these respects, but when the latter group was further subdivided into primary generalized epilepsy and focal non-temporal lobe epilepsy, the focal groups (both temporal lobe and non-temporal lobe) were more impaired. Hormonal analysis confirmed earlier hospital-clinic-based reports. In the epilepsy group, plasma free testosterone and percentage free testosterone values were decreased, sex hormone binding globulin, luteinizing hormone (LH) and follicle stimulating hormone (FSH) were increased compared to values in a normal healthy population. As association between the behavioural and hormonal indices of hyposexuality was shown, particularly for LH, but this was less apparent than in previous work.

Adolescent↗

Synthesis and biological activity of luteinizing hormone-releasing hormone and related peptides.

Syntheses of the decapeptide luteinizing hormone-releasing hormone, less thanGlu-His-Trp-Ser-Tyr-Gly-Leu-Arg-Pro-Gly-NH2 are described. The basic properties of arginine can provide a simple repetitive isolation procedure for arginine-containing peptides. The biological activities of the decapeptide, of a range of fragments and modified fragments, and of two analogs with alteration in the series at position 4 were measured by in vitro incubation with sheep pituitary slices, measuring the liberated LH by bioassay. None of the compounds of shortened sequence were active, with the exception of less thanGlu-His-Trp which showed 1% of the decapeptide in one of four experiments. Neither [Ser(But)4]-LH-RH-nor [Leu4]-LH-RH showed significant activity indicating (despite the known activity of [Ala4]-LH-RH) the importance of this part of the structure for full biological activity.

Amino Acid Sequence↗

An inexpensive method for assessing pituitary response to luteinizing hormone releasing hormones: analysis of serum gonadotropins in pooled samples.

Sixty-two children, aged 2-18 years, suspected of an endocrine disorder were given one of several IM injections of the LHRH and the blood was drawn prior to and at 30, 60, 90, 120, 240 minutes after the injection. An aliquot of .2 ml of serum was taken from each post-LHRH specimen and pooled. The gonadotropins were measured in all the individual and pooled samples. A high correlation (r = .974, LH; r = .981, FSH) between the peak and the pooled sample suggests that the analysis of gonadotropins in a pooled sample gives information comparable to that obtained by the gonadotropin analysis in multiple serum samples. A formula to calculate the peak LH and FSH from the pooled specimen taken from only four post-LHRH injections is: peak LH = 3.015 + 1.049 times the pooled LH; peak FSH = 3.153 + 1.072 times the pooled FSH value. The correlation coefficient between the observed and the calculated LH was .98; the same for the FSH was .987. I suggest that the pooled sample, due to it's integrated response, is a better reflection of the pituitary response to the LHRH.

Adolescent↗

[Rational hormonal diagnosis of secondary amenorrhea].

The usefulness of the guideline recommended in 1976 by the World Health Organization (WHO) for the differential diagnosis of ovarian sterility needs critical reevaluation, since it does not take into account new aspects such as the pulsatility of GnRH secretion, androgen excess, or thyroid disorders and other phenomena related to ovarian dysfunction. In order to demonstrate the relative frequency of such phenomena, the authors examined 183 women with secondary amenorrhea of more than three months' duration (mean +/- SD = 12.7 +/- 18.4 months). The endocrine status of these women was examined under standardized conditions in two clinical endocrinology units in the cities of Hamburg and Berlin. The percentages of abnormal hormonal data (greater than mean +/- SD + gray zone) were as follows: testosterone (T) 39.9%; DHEA sulfate (DS) 29.5%; prolactin (PRL) 18.0%; TSH 11.5%; FSH or LH 26.8%; estradiol (E2) 30.1%. Among 96 patients with increased T and/or DS (52.5% of all patients), 53 patients (55.2%) did not show any clinical signs of androgenization (hirsutism, acne). Retrospective evaluation of all data revealed that a stepwise diagnostic procedure would have resulted in the following cumulative percentages of hormonal abnormalities: (1) T = 39.9%; (2) +DS = 52.5%; (3) +PRL = 60.2%; (4) +LH/FSH = 82.0%; (5) +E2 = 91.2%; (6) +TSH = 92.3%. Only in 7.7% of all patients were all hormonal parameters within normal ranges. Individual case analysis showed that 52.5% of all patients had hyperandrogenemia, while 18% had hypothalamic amenorrhea without any other pathologic condition; 17.5% had hyperprolactinemia and 3.3% primary ovarian insufficiency. Another 4.9% had hypothyroidism only, while 1.1% had exclusively hyperthyroidism. Combined hormonal deviations were found in 24% of all patients. Considering the differential diagnosis of secondary amenorrhea from an economic point of view, one comes to the conclusion that direct and indirect expenditures are similar in magnitude, no matter whether one prefers a conventional stepwise procedure or a one-step hormonal analysis encompassing all potentially relevant hormones (DM 859.00 + 10 weeks waiting time vs. DM 827.50 + 1 week waiting time). Androgen excess is much more frequent than was believed; hirsutism and/or acne by no means necessarily occur in cases of androgen excess. Hyperprolactinemia is less frequent than hyperandrogenemia. Thyroid status should be evaluated in all women with functional amenorrhea. The stepwise diagnostic procedure as recommended by the WHO is time-consuming, complicated, and sometimes incomplete in the diagnostic work-up, with obvious potential disadvantages for therapy.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗

Negative feedback regulation of gonadotropin secretion by androgens in fetal rhesus macaques.

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)

Animals↗

Ovarian follicular dynamics in the llama.

Ovarian follicular dynamics were determined in adult llamas by ultrasonography and palpation per rectum and hormone analysis (estradiol-17 beta and estrogen conjugates) of plasma and urine. The relationship of gonadotropin secretion to follicular development was determined by the analysis of plasma FSH and LH concentrations. Progesterone analysis of plasma was used to verify or deny the presence of CL. Final follicular development (from 3 mm) averaged 4.8 days, while the duration of the mature follicle (8-12 mm) averaged 5.0 days; regression of the follicle occurred over about 4 days. The development of a subsequent dominant follicle usually began within 2-3 days after onset of regression of the dominant follicle. While several follicles were present at the time of the demise of the dominant follicle, only one follicle continued to develop. The interval between ovarian follicle waves averaged 11.1 days. Dominant follicle activity alternated between ovaries in 81% of the cycles. The occurrence of dominant follicles was evenly distributed between ovaries. While plasma estradiol and estrogen conjugate concentrations were positively associated (p less than 0.05) with follicular activity, urinary estrogen conjugate concentrations best reflected ovarian follicular dynamics (p less than 0.001). Daily FSH concentrations in plasma were not correlated with follicular activity. LH concentrations in plasma were low in all animals throughout the study, indicating estrogen from developing ovarian follicles does not induce the release of LH. Progesterone values were low during the study, indicating that the llama does not spontaneously ovulate, at least under the conditions of this study. In summary, llamas have overlapping ovarian follicle waves that occur at about 11-day intervals.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Testicular volume, semen profile and serum hormone levels in fertile Thai males.

The fertility profile of 307 Thai male volunteers whose wives were currently in early pregnancy was established by genital examination, semen analysis and serum hormone analysis. Ninety percent of the subjects had testicular volumes of 12-25 ml (mean 17.2 ml) which was found to relate to body weight, height and the ponderal index as well as to the sperm count. However, values for semen analysis were significantly below the recognised standard for Caucasian males. There was an inverse relationship between testicular volume and the serum concentration of FSH, LH and prolactin. It is suggested that a common protocol for male fertility assessment should be used to establish standard parameters for racially different male populations.

Adolescent↗

Hormonal response to electrocautery of the ovary in patients with polycystic ovarian disease.

Fifty-eight women with polycystic ovarian syndrome (PCO) were treated with electrocautery of the ovarian capsule and then studied by hormone analysis for 12 months. In 72% ovulation appeared to occur within 4 weeks and in this group mean serum LH and FSH levels showed a statistically significant increase the day after electrocautery, followed by a gradual decline in LH to a level significantly below the pretreatment value. No changes in LH and FSH were seen in those who did not ovulate. The mean levels of testosterone, androstenedione and dihydrotestosterone which were in the upper normal range or slightly above before treatment were significantly reduced after electrocautery. Serum oestradiol levels showed a significant increase after 1 week, when progesterone levels were still unchanged, suggesting that follicular development was already in progress. The mean serum level of sex hormone binding globulin was slightly below the normal range before treatment and then increased gradually. Endocrine responses to electrocautery were similar to those described previously after wedge resection. The simplicity of this treatment and the good response make it an attractive alternative for treating infertility associated with PCO.

Androstenedione↗

Hormone studies in females with androgenic hairloss.

Reports on hormone analysis in androgenic hairloss in the female show partly contradicting results. Elevated as well as normal-range androgen levels have been found. The present study aimed at the investigation of a possibly more differentiated hormonal constellation by hormone analysis and additional determination of the hypophyseal level by the thyrotropin-releasing hormone (TRH) test. In 46 female patients with androgenic hairloss blood sampling for hormone analysis was performed. Determination of the androgens testosterone (T), androstenedione (A), dehydroepiandrosterone sulfate (DHEAS), 17-hydroxy-progesterone acetate (17-OHP) and free testosterone (FT), of sex-hormone-binding globulin (SHBG), estradiol (E2), cortisol (F) and the hypophyseal luteinizing hormone (LH) and follicle-stimulating hormone (FSH) was performed by standard radioimmunoassay methods. The TRH-test is based on feedback mechanisms between the hypothalamic TRH which stimulates hypophyseal TSH and PRL release. Thus, even mild forms of hypothyroidism or hyperprolactinaemia can be detected. The control group for the TRH test consisted of 45 volunteer females without hairloss or any other hormonal or menstrual disturbances. Statistical analysis was performed according to the Wilcoxon two-sample test. The results of the study show no significant elevation of androgens in females with androgenic hairloss, but a more complex condition with involvement of the glandula suprarenalis and the hypophyseal level. Significantly elevated TSH levels prior to and after TRH stimulation in the hairloss group indicate that hypothyroidism may be an important hormonal disturbance in androgenic hairloss. Interactions between hypothyroidism and androgen metabolism are possible at various links.(ABSTRACT TRUNCATED AT 250 WORDS)

17-alpha-Hydroxyprogesterone↗

Hormone serum levels and hormone receptor contents of endometria in women with normal menstrual cycles and patients bearing endometrial carcinoma.

Serum levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), prolactin (HPRL), 17 beta-estradiol (E2) and progesterone (P) were estimated in 46 subjects with normal menstrual cycles in whom hysterectomies were performed. Estrogen (ER) and progesterone receptor (PgR) levels in endometrial samples of these patients were estimated, and histological dating of the cycle day was carried out. Similarly, hormone serum levels and ER as well as PgR were estimated in 17 patients with endometrial carcinoma. No correlation between LH, FSH, HPRL and ER as well as PgR was noted in the normal subjects. Correlation between P and ER was observed in this group. Parallel variations between E2 and PgR were recorded in the normal females. In the carcinoma group no correlations between hormone serum levels and receptor contents were found, but ER and PgR correlated with each other. Receptor levels was highest in the well-differentiated group of endometrial carcinoma. The present experiments provide a rationale for progestagen therapy of carcinoma of the endometrium.

Endometrium↗

Direct pituitary effects of testosterone and luteinizing hormone-releasing hormone upon follicle-stimulating hormone: analysis by radioimmuno- and radioreceptor assay.

The present studies examine the effects of testosterone (T) and LHRH, alone or in combination, on the amount of FSH secreted by pituitary cells in culture. FSH was quantified by RIA and radioreceptor assay (RRA). Half of the cultures were exposed to T for 3 days. The remainder served as controls. Each of these two groups was divided in half and exposed to medium only or LHRH (10(-8) M) for 4 h. Medium was collected from all cultures after 3 days +/- T (medium 1) and after 4 h +/- LHRH (medium 2). After medium 2 collection, cell homogenates were prepared. In a second study, T-treated cell cultures also received 0, 0.5, or 5.0 micrograms/dish tunicamycin for the last 16 h of the 3-day incubation. During the 3 days of culture, the T-treated group secreted greater amounts of immunoactive FSH than controls. However, LHRH-induced FSH release measured by RIA was blunted as a result of T exposure compared with untreated controls. T treatment elevated intracellular immuno-FSH stores. Each sample was quantitated for FSH activity by RRA, and the FSH RRA/RIA was calculated. T and/or LHRH treatment, while eliciting FSH hypersecretion, caused a reduction in the RRA/RIA of secreted FSH. Changes in the RRA/RIA are thought to occur as a result of alterations in the glycosylation of FSH. To test this hypothesis, T-treated cells were exposed to tunicamycin, a drug that reduces the rate of glycosylation of secreted proteins. Exposure of cells to this drug prevented the reduction in the RRA/RIA of secreted FSH caused by T and/or LHRH. FSH secreted from control, T-treated, or T-treated plus tunicamycin-exposed cells was examined by isoelectric focusing. T-Treated cells released a greater proportion of FSH forms with lower isoelectric points (indicative of a greater degree of glycosylation) compared with controls. Tunicamycin exposure reversed T's effect upon the isoelectric profile. These studies demonstrate a direct pituitary action of LHRH and T upon the type of FSH released. During times of hormonally induced increases in the rate of FSH secretion, the pituitary releases FSH forms that are more heavily glycosylated, exhibit a lower isoelectric point, and show a reduced RRA/RIA. FSH secreted after T treatment would be expected to have an increased plasma half-life due to the protective effects of the sugar residues. Thus, the existing hormonal milieu exerts a multidimensional effect upon FSH released by pituitary cells in culture that cannot be appreciated by RIA assessment alone.

Animals↗