Outcome from consecutive ICSI cycles in patients treated with recombinant human LH and those supplemented with urinary hCG-based LH activity during controlled ovarian stimulation in the long GnRH-agonist protocol.

Clinical results were compared in a well-established, assisted reproduction program during the cross-over from highly purified (HP)-human menopausal gonadotropin (hMG) to rhFSH/rhLH. We included the last 33 patients treated with HP-hMG and the first 33 patients receiving rhFSH/rhLH for ovarian stimulation in their first intracytoplasmic sperm injection cycle. Patient baseline characteristics were almost identical in the two groups. Ovarian stimulation characteristics (days of stimulation, total amount of FSH administered using a modest initial loading dose of 150 IU/d, patients with oocyte retrieval) were similar for the two groups. However, the number of total and leading follicles and E2 serum levels on the human chorionic gonadotropin injection day were significantly higher in the rhFSH/rhLH group. The oocyte yield was significantly higher in the rhFSH/rhLH group as well as the number of metaphase II oocytes, difference almost reaching the statistical significance. The number of oocytes fertilized was also higher in patients receiving rhFSH/rhLH treatment. Implantation and clinical pregnancy rates were similar in both the study groups. It is concluded that in women undergoing controlled ovarian hyperstimulation under pituitary suppression for ART, the recombinant combined product containing FSH and LH in a fixed 2:1 ratio is more effective than HP-hMG in terms of follicle development, oocyte yield and quality, and fertilization rates.

Monthly gonadotropin cycles in premenarcheal girls.

Patterns of nocturnal excretion of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) were investigated in 11 girls. Autoregressive digital filtering of low- and high-frequency variations was used to make patterns more apparent. Coincident FSH and LH surges, separated by an interval of 20 to 40 days, were seen in specimens from three of six postmenarcheal girls and three to five premenarcheal girls. This suggests that cyclic hypothalamic-pituitary-ovarian interactions occur before menarche.

Urinary hormone levels during the natural menstrual cycle: the effect of age.

A number of studies have identified hormonal changes in women during their reproductive lifespan, many focusing upon changes in women over the age of 40 years. The present study has determined the effect of increasing age on hormone levels over three decades. Daily early morning urine samples were assayed for estrone-3-glucuronide (E3 G), pregnanediol-3-glucuronide (P3 G), testosterone-17-glucuronide (T17 G), FSH and LH. An examination of the validity of using creatinine as a volume adjuster in urine samples formed an integral part of the analysis. Volunteers were healthy women who had regular (25-35 days) cycles, were not taking oral contraceptives, hormone therapies or any other medication. Three age groups were compared: 20-29 years (n=13), 30-39 years (n=9) and 40-49 years (n=13). Statistical analyses were carried out using two-way ANOVA and post hoc t-tests. Creatinine excretion, despite revealing no cycle-related variation in any age group, showed a decline with increasing age. Creatinine output was significantly lower in the 40-49 years age group in all phases of the cycle than in the 20-29 and 30-39 groups (P<0.0001). Uncorrected levels of E3 G were significantly higher in the 30-39 years group when compared with the 40-49 age group (P<0.0001). Uncorrected P3 G output was significantly higher in women aged 20-29 years than in women aged 40-49 years (P<0.001) and levels of uncorrected T17 G were higher in the 20-29 year age group when compared with the 30-39 or 40-49 years age group (P<0.0001). The present study is consistent with previous reports that have revealed a decline in creatinine clearance with increasing age, and therefore casts into some doubt the validity of using creatinine clearance as a procedure to correct for volume fluctuations in differing age groups of women. The study also demonstrates unequivocally that age-related variations in hormone levels are not restricted to women over 40 years of age. The novel finding of highly significant differences in mean levels of T17 G between the age groups is of considerable interest. It is presently unclear whether this resulted from specifically increased ovarian and/or adrenal secretion. The possible impacts of changes in testosterone levels during the female reproductive lifespan merits further study.

Further evidence for insulin hypersecretion not as an initial event but as a consequence of body growth and maturation in juvenile-onset obesity.

According to our previous study, hyperinsulinism develops not before 10 years of age despite the presence of obesity but during the maturation years of 10-20. We aimed here at examining the growth-related islet B-cell change together with pituitary activity in non-familial juvenile obesity. Measurement of 24 h urine hormones was shown to be useful for evaluation of the diurnal hormones in plasma. In 56 non-obese and obese juveniles, a significantly positive correlation was found between age (6-18 years) and 24 h urine insulin and c-peptide, thus indicating that the age-related absolute value of body weight significantly affects insulin and c-peptide excretions both in non-obese and obese subjects. Consequently, urinary insulin and c-peptide excretions per kg of body weight were highly similar between obese and non-obese juveniles. However, when the lower specific gravity of fat mass compared with lean body mass and the relative shortage of circulating plasma in fat tissues are taken into consideration, it is obvious that obesity by itself specifically augments this physiologic B-cell maturation between 10 and 20 years of age. The possible interactions of growth hormone and pituitary gonadotropin in hyperinsulinism are discussed.

Ovarian-pituitary hormone interactions during the perimenopause.

To describe the hormone changes that occur at the onset of the perimenopause, daily urine and random blood samples were collected from 5 peri-menopausal women for 3 or 4 consecutive cycles. Estrone conjugate and pregnanediol-3-glucoronide concentrations were determined for urine samples. Circulating luteinizing hormone, follicle stimulating hormone, progesterone, estradiol and estrone concentrations were determined in serum samples. Two of the 5 women experienced irregular menstrual intervals during the study period. One of these subjects experienced a prolonged intermenstrual interval. Three other women exhibited apparently regular ovulatory menstrual cycles. The prolonged intermenstrual interval of one women exhibiting irregular menstrual intervals was associated with low urinary estrogen levels in the early follicular phase of the affected cycle, followed by increased gonadotrophin levels and increased estrogen levels that rose to exceed normal cycle concentrations by 2- or 3-fold. Increased estrogen levels were followed by declining gonadotrophin levels, minimal progesterone production, and, ultimately, vaginal bleeding. These data suggest that there are some forms of menstrual variability at the time of the perimenopause associated with lowered early follicular phase estrogen levels. Reduced negative feedback and subsequently increased gonadotrophin levels may have stimulated estrogen production which may have suppressed gonadotrophin secretion and lowered estrogen excretion, resulting in the observed oscillations between episodes of hypo- and hyperestrogenism.

Measuring endocrine profiles of women in field studies.

Improved methods are needed to evaluate the effects of occupational and environmental hazards on the reproductive health of human female populations. This communication describes highly specific, sensitive, and reliable time-resolved fluorescence immunoassays for measuring luteinizing hormone (LH) and follicle-stimulating hormone (FSH), estrone 3-glucuronide (E13G), and pregnanediol 3-glucuronide (Pd3G) in urine, a fluid that is convenient and painless to collect serially from large populations. Furthermore, some of the technical issues relevant to the successful application of these measurements to field studies are discussed.

[Pubertal development after pediatric heart transplantation]. / Développement pubertaire après la greffe cardiaque pédiatrique.

Twenty-one children and adolescents underwent orthotopic cardiac transplantation at the Hôpital Sainte-Justine between July 1984 and June 1993. Of those patients, 16 (4 girls and 12 boys) who survived more than one year after the procedure were followed prospectively for documentation of onset and progression of puberty. The immunosuppressive therapy included cyclosporine, azathioprine and prednisone. Subjects were evaluated at 6 month intervals for the study of: pubertal development according to staging by the method of Marshall and Tanner and hormonal profile (FSH, LH, testosterone, DHEAS). Despite a stagnation of pubertal signs before surgery, puberty carried on and progressed normally postoperatively. The urinary levels of gonadotropins rose to adequate levels for age. Testosterone levels in boys were related to the progression of secondary sexual characteristics. Levels of DHEAS were drastically reduced, most likely because of the supraphysiological doses of oral glucocorticoids. Our results indicate that after pediatric heart transplantation, puberty progresses normally at adolescence.

Enhanced hypothalamic-pituitary sensitivity to estrogen in premenopausal women with diminished ovarian reserve compared with older perimenopausal controls.

OBJECTIVE: We have previously characterized the reproductive hormone profile in infertile women with diminished ovarian reserve (DOR) as being distinct from that seen in age-comparable healthy controls. Hypothesizing that DOR reflects accelerated reproductive aging, we herein compare urinary reproductive hormone dynamics between young women with DOR and a population of chronologically older perimenopausal controls. METHODS: In this prospective observational study, urinary levels of pituitary gonadotropins (follicle-stimulating hormone and luteinizing hormone) and metabolites of estrogen (estrone conjugate) and progesterone were assessed in daily morning urine samples collected in a spontaneous menstrual cycle in 8 infertile premenopausal women with DOR and in 11 perimenopausal controls. Areas under the curves were calculated for the respective measured hormones, and comparisons were made using the Mann-Whitney U test. RESULTS: Urinary estrone conjugate levels were significantly attenuated in premenopausal women with DOR compared with the older perimenopausal cohort. Despite the relatively lower estrogen, a significantly more pronounced luteinizing hormone surge was evident in the younger population. Early follicle-stimulating hormone was lower in women with DOR, but luteal urinary progesterone excretion was comparable in the two groups. CONCLUSIONS: Our data suggest distinctions in functioning of the central (hypothalamic-pituitary) and peripheral (ovarian) components of the hypothalamic-pituitary-ovarian axis in premenopausal women with DOR compared with chronologically older perimenopausal controls. Increased hypothalamic-pituitary sensitivity to estrogen positive feedback is suggested in premenopausal women with DOR. Our observations identify DOR as a distinct entity in the paradigm of reproductive senescence.