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Exaggerated prolactin response to thyrotropin-releasing hormone in infertile women with the luteinized unruptured follicle syndrome.

Ten cases of luteinized unruptured follicle (LUF) syndrome out of 250 women with unexplained infertility were detected on ultrasonography, giving a frequency of 4%. Hormonal analysis revealed lower serum progesterone levels at mid-luteal phase in LUF cases, suggesting a link between LUF syndrome and inadequate luteal phase. Prolactin response to thyrotropin-releasing hormone was exaggerated in LUF cases as compared with ovulatory cases. Aberrant prolactin release may be a contributory factor in the pathophysiology of the LUF syndrome.

Anovulation↗

Gonadotropin suppression with oral contraceptives before in vitro fertilization.

One hundred eighty-one stimulation cycles in which gonadotropin suppression with oral contraceptives (OCs) preceded induction of follicle stimulation (study group) and 113 stimulation cycles without pituitary suppression (control group) were compared. The mean length of ovarian suppression was 35.3 +/- 0.9 days. No spontaneous luteinizing hormone (LH) surges occurred when the use of OC preceded ovarian hyperstimulation, whereas in the control group the incidence of LH surges was 19.5%. The mean amount of human menopausal gonadotropin required was significantly lower in the study group than in the control group (8.9 +/- 0.4 and 10.9 +/- 0.4 ampules, respectively). Significantly more follicles greater than or equal to 1.5 cm in diameter were seen on the day before oocyte retrieval and significantly more oocytes were retrieved per attempt in the group with OC pretreatment. Our data clearly demonstrate that OCs are useful in vitro fertilization stimulation protocols to facilitate scheduling of cycles and to prevent spontaneous LH surges.

Abortion, Spontaneous↗

Long-term treatment of hirsutism: desogestrel compared with cyproterone acetate in oral contraceptives.

OBJECTIVE: Effectiveness of 2-year treatment of hirsutism with low estrogen oral contraceptives (OCs) containing nonandrogenic or antiandrogenic progestogen. Evaluation of changes in plasma lipids. DESIGN: Ten patients treated with desogestrel 150 micrograms + 30 micrograms ethinyl estradiol, 6 with desogestrel 150 micrograms + 50 micrograms ethinyl estradiol, 10 with cyproterone acetate 2 mg + 35 micrograms ethinyl estradiol. Random allocation. Paired comparisons. CONTROL GROUP: 19 normal women, not treated. SETTING: Academic tertiary care. PATIENTS: Women with hirsutism (idiopathic and/or polycystic ovary), 24 of 26 completed treatment. INTERVENTION: Two-year treatment. MAIN OUTCOME MEASURES: Hirsutism score, plasma testosterone, and lipids. RESULTS: Initial hirsutism scores (11.8 +/- 0.6 SE) declined with treatment (-7.2 +/- 0.4, P less than 0.01) to 4.7 +/- 0.6, almost reaching control (3.6 +/- 0.3). Initial plasma cholesterol (4.33 mmol/L +/- 0.30 SE), similar to control (4.78 +/- 0.24), increased slowly over 2 years (+2.04 +/- 0.34, P less than 0.01). High-density lipoproteins cholesterol (1.05 mmol/L +/- 0.04 SE), similar to control (1.12 +/- 0.07), did not change the 1st year and increased at 2 years (+0.57 +/- 0.11, P less than 0.01). No differences appeared among treatment groups. CONCLUSIONS: Treatment is very effective, 2 years for best results. The OCs tested are equally efficacious. Changes in plasma lipids are of some concern but of difficult interpretation.

Adult↗

Combination of 19-nortestosterone-hexyloxyphenylpropionate (Anadur) and depot-medroxyprogesterone-acetate (Clinovir) for male contraception.

Because monotherapy with 19-nortestosterone hexyloxyphenylpropionate (Anadur, Pharmacia Arzneimittel, Ratingen, Federal Republic of Germany) suggested improved results for male contraception compared with available testosterone esters, it was tested for induction of complete azoospermia when combined with depot-medroxyprogesterone acetate (DMPA, Clinovir, Upjohn GmbH, Heppenheim, Federal Republic of Germany). Twelve men were treated for 7 weeks with weekly intramuscular (IM) injections of 200 mg Anadur followed by 3-weekly IM injections of Anadur up to week 15. Clinovir (250 mg) IM was administered at the start of treatment and during weeks 6 and 12. Anadur and Clinovir suppressed serum gonadotropins. Although serum testosterone declined steeply, in general, libido and potency were not impaired. Sperm concentrations were reduced significantly after 3 weeks of treatment. Lowest sperm counts were seen during week 8 of follow-up, when only 2 volunteers showed measurable sperm counts of 2.1 and 3.0 X 10(6)/ml, with a declining tendency. After 43 weeks, sperm concentrations were still below pretreatment range in 2 men, but later returned to pretreatment values. Computerized sperm motion analysis revealed that motility parameters in the residual sperm were reduced. In vitro analysis excluded a direct effect of medroxyprogesterone acetate in seminal plasma on sperm motion. The data indicate that the combination of Anadur with Clinovir increases the rate of azoospermia in normal volunteers seen under Anadur monotherapy, although the goal of azoospermia in all participants was not quite achieved.

Anabolic Agents↗

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↗

[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↗

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↗

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↗

Detection of ovulation by a radioreceptor assay for human luteinizing hormone.

A specific, sensitive, and rapid radioreceptor assay (RRA), employing membranes from bovine testes as receptor and [125I]hLH as radioligand, has been developed for measurement of human LH in serum. This RRA was used to determine the time of ovulation in seven women. For comparison, four hourly values around midcycle were measured by RIA. The sensitivity of the RRA was 0.78 ng/ml serum and could be increased by prolonged incubation. The coefficient of within and between assay variation at the 50% inhibition level was 7% and 13%, respectively. The mean index of discrimination (RRA/RIA) was 1.02, expressed by the slope of the regression curve. The coefficient of correlation was 0.97. In all women, the LH surge was detected by RRA, and the subsequent ovulation was verified within 30 h by endoscopic examination of the ovaries, as well as serum progesterone concentrations of more than 5 ng/ml on the fifth day after ovulation. As shown, prospective ovulation timing can be done by this simple and accurate method. The RRA can be useful in infertility therapy such as artificial insemination.

Adult↗

Plasma levels of adrenocorticotropin and cortisol in women receiving oral contraceptive steroid treatment.

The secretion rate and plasma concentration of the adrenocortical steroid cortisol is modified in subjects treated with estrogenic and/or progestational steroids. The effects of contraceptive steroids on the secretion of ACTH are poorly documented, however, In the current investigation, we found that concentrations of ACTH and cortisol in plasma obtained at 0800--0900 h from a group of women with normal cyclic menses (n = 4) ranged from 78--120 pg/ml and 77--137 ng/ml, respectively. Although significant cyclic changes in the plasma levels of LH, FSH, 17 beta-estradiol, and progesterone occurred during the ovarian cycle, no obvious cyclic fluctuations in plasma levels of ACTH or cortisol were observed. In women treated with Norinyl 1 + 80 (1.0 mg norethindrone plus 0.08 mg mestranol), plasma concentrations of LH, FSH, 17 beta-estradiol, and progesterone were significantly lower (P less than 0.001) than plasma levels of these hormones in normal women during the ovarian cycle. The mean daily plasma concentrations of ACTH were significantly lower (P less than 0.001), whereas plasma cortisol levels were significantly higher (P less than 0.001) in women treated with oral contraceptive steroids compared to the levels of these hormones in the untreated ovulatory women.

Adrenocorticotropic Hormone↗

Evaluation of danazol as an oral contraceptive.

The effect of Danazol as an oral contraceptive in doses of 50, 100, and 200 mg daily for 6 months was studied in 3 groups of 10 women. Both 50 and 100 mg Danazol daily were well tolerated, but one pregnancy occurred among the women receiving 50 mg daily, and 2 pregnancies occurred in women receiving 100 mg daily. There were no pregnancies in women taking 200 mg Danazol daily; however, the side effects were frequent and 5 of the 10 patients withdrew from the study prior to 6 months of therapy. Six patients in this study were followed intensively with blood hormone analysis, vaginal cytology, and pathologic evaluation, and these findings are detailed.

Acne Vulgaris↗

[Comparative characterization of radioimmunologic and non-isotopic methods of hormonal analysis].

Measurements of 8 hormones (prolactin, FSH, LH, thyrotropic hormone--TTH, estradiol, hydrocortisone, thyroxine, and triiodothyronine--T3) were carried out by the Amerleit system and radioimmunoassay. The hormones were measured in the same blood plasma samples of patients with various endocrine conditions, admitted for examinations to the Endocrinology Center of the Russian Academy of Medical Sciences. Employment of the Amerleit system for hormonal analysis helps obtain the results compatible with the results of RIA for the majority of the measured hormones. The methods for measuring LH, estradiol and T3 are to be improved. The Amerleit system is highly productive and permits getting the results within 3 hrs. A trained laboratory assistant can measure the hormonal levels in 120-160 blood samples within a day. High efficacy of the technology is indispensable in realization of the screening programs. The absence of radioactivity, safety, high productivity, reliability, accuracy and good storage of the kits (up to 6-8 months) are the principal advantages of the Amerleit system over the existent radioimmunologic systems.

Estradiol↗

Bovine cystic ovarian disease: plasma hormone concentrations and treatment.

Ovarian function in 91 dairy cows with cystic ovarian disease was assessed by rectal palpation and by plasma hormone analysis before and after treatment. Plasma analysis showed that 84% of the cysts were correctly classified clinically and only these cows are considered further. Luteinised cysts occurred in 59 cows whereas only 18 had non-luteinised cysts. The mean plasma concentrations of luteinising hormone (LH), follicular stimulating hormone (FSH), progesterone, oestradiol and testosterone were not significantly different when compared with values at relevant stages of the oestrous cycle in normal cows. Success of treatment with progesterone, a synthetic prostaglandin, human gonadotrophin (HCG), or gonadotrophin releasing hormone (GnRH) was not dependent upon prior hormone concentrations, except for the prostaglandin which required active luteal tissue. LH and FSH concentrations in cows with luteinised cysts were not significantly different before and after successful treatment with GnRH or progesterone. Normal luteal function was not always established after treatment of non-luteinised cysts with GnRH.

Animals↗