Thomas Laml

Premature ovarian failure: etiology and prospects

A search of past and current articles on ovarian physiology and premature ovarian failure (POF) using MEDLINE was performed in order to present an overview of clinical manifestations, necessary laboratory investigations, possible etiologies and treatments for POF. POF is defined as gonadal failure before the age of 40 years. Initially, POF was thought to be permanent, but it is now believed that spontaneous remissions and even pregnancies are possible in affected women. In most cases, the etiology of POF remains elusive, but several rare specific causes have been identified. Although the etiology of POF is heterogenic, the treatment principles are the same. Hormone replacement therapy (HRT) is still the cornerstone of treatment. The only proven method of obtaining a pregnancy in patients with POF is fertilization of a donor oocyte. Cryopreservation of oocytes has worked well in animals but awaits refinement before it can be applied routinely to humans with prodromal POF, or to patients before chemotherapy or irradiation in order to save their oocytes for future fertilization. New alternatives to traditional HRT and methods of fertility preservation are under development, but understanding of the basic pathophysiology of POF is necessary for the development and use of innovative treatments.

Maternal Serum Leptin Concentrations Do Not Correlate With Cord Blood Leptin Concentrations in Normal Pregnancy

Objective: To determine whether there is a difference in maternal leptin concentration and cord blood concentration, consistent with the hypothesis of a noncommunicating, two-compartement model of fetoplacental leptin regulation. Methods: Blood samples were collected from 139 women, identified as having an uncomplicated pregnancy, from an antecubital vein at delivery. Cord blood samples were taken from the umbilical vein. Leptin was measured by radioimmunoassay, and its relationship to fetal and maternal anthropometrics was assessed by Spearman correlation. Differences in maternal and cord blood leptin levels between male and female infants were tested twith the Mann-Whitney U test. Maternal and cord blood leptin were compared by the Wilcoxon signed rank test. The outcome measures were maternal and cord blood leptin at delivery, fetal birth weight, length, weight/length ratio, and ponderal index, maternal prepregnancy body mass index, pregnancy weight gain, relative weight gain, and body mass index at delivery. Results: No correlations were found between maternal and cord blood leptin concentrations. Fetal leptin level correlated with birth weight (ρ = 0.665; p < .0001), length (ρ = 0.490; P < .0001), ponderal index (ρ = 0.260; P = .002), and weight/length ratio (ρ = 0.625; P < .0001). Median leptin concentrations were higher in female (9.3 ng/mL, range 1.5-34.4 ng/mL) than in male (8.2 ng/mL, range 1.6-38.3 ng/mL) neonates, but this difference was statistically not significant. Logistic regression analysis showed a significant influence on umbilical venous leptin concentration for birth weight (P < .0001) but not for gender. Maternal leptin concentrations were significantly higher than cord leptin concentrations (P < .0005 for the male and female neonates and the entire group). Conclusion: There was no correlation between maternal and cord leptin, whiich supports the hypothesis of a noncommunicating, two-compartment model of fetoplacental leptin regulation.

Androgen Serum Levels in Women with Premature Ovarian Failure Compared to Fertile and Menopausal Controls

OBJECTIVE The purpose of our study was to examine androgen serum levels and bone density in women with premature ovarian failure (POF) compared to healthy normal controls. STUDY DESIGN Thirty-three women 19-35 years of age with idiopathic POF were compared to 33 well-matched women with normal ovarian function and 32 healthy postmenopausal (PMP) women concerning 17-hydroxyprogesterone (17-OHP), androstendione (A), testosterone (T), dehydroepiandrosterone-sulfate (DHEAS), insulin-like growth factor 1 (IGF-1), as well as bone density (BD). RESULTS Women with POF showed statistically significantly lower concentrations of 17-OHP, A, T (p < 0.001) and a reduced bone density (p < 0.001) compared to fertile controls. No differences were found between POF and PMP women concerning estradiol (E2), T, A and 17-OHP. Regarding DHEAS, no statistically significant differences were found between women with POF and fertile controls whereas PMP women proved to have significantly lower DHEAS concentrations than fertile controls. Women with POF had the highest IGF-1 serum concentrations and PMP women the lowest. CONCLUSION An important decrement of ovarian steroids and bone density was noticed in women with POF, while the time since menopause had no influence on androgen concentrations. The hormone concentrations in women with POF are similar to those observed in normal PMP women with the exception of DHEAS and IGF-1 levels.

The urethra during pelvic floor contraction: Observations on three-dimensional ultrasound

OBJECTIVE To investigate with three‐dimensional ultrasound how voluntary pelvic floor contractions influence the morphology of the female urethras components. METHODS Twenty female patients with benign gynecologic disorders (mean age: 29 years; range: 19–40) had transrectal sonography using a 7.5‐MHz mechanical sector endoprobe with three‐dimensional features during both pelvic floor muscle relaxation and pelvic floor muscle contraction. The multiplanar display of the scanned volumes allowed detailed morphologic assessment of the urethra and the measurement of distances and volumes of the urethral components. Statistical end points were maximum sagittal and transverse urethral diameter, maximum sphincter length and thickness, maximum smooth muscle thickness, and the volumes of the sphincter, the smooth muscle, and the entire urethra. RESULTS All 20 rectal scans were feasible. Two patients had to be excluded from analysis because of poor image quality, leaving 18 patients for evaluation. When compared with pelvic floor relaxation, the following measures were smaller during pelvic floor contraction: sagittal urethral diameter (10.4 versus 11.5 mm; P = .004), transverse urethral diameter (14.1 versus 15.0 mm; P = .009), urethral sphincter thickness (2.4 versus 2.7 mm; P = .012), urethral sphincter volume (0.5 versus 0.6 mL; P = .003), and total urethral volumes (1.4 versus 1.5 mL; P = .007). Sphincter length and smooth muscle thickness, as well as smooth muscle volume, did not change significantly during pelvic floor contraction. CONCLUSION On three‐dimensional ultrasound, the morphologic changes of the female urethra during pelvic floor contraction suggest external compression of the urethra rather than contraction of the sphincter muscle.

Effects of hormone replacement therapy on growth hormone secretion patterns in correlation to somatometric parameters in healthy postmenopausal women

OBJECTIVES The aim of the present study was to investigate the influence of a continuous estrogen, cyclic progesterone replacement therapy on the secretion of growth hormone (GH) and IGF I as well as of somatometric-GH correlation patterns. METHODS The study included 23 healthy postmenopausal women. Of the proband group 13 randomly selected women were treated with orally applicated 2 mg estradiol-valerat (E2V) and 10 mg dydrogesterone for 10 months. Ten women did not receive any hormonal treatment during this time. After 10 months all probands were reexamined and their GH and IGF I secretion, as well as their somatometric-hormonal correlation patterns, compared with those of a fertile control group. RESULTS It could be shown, that in postmenopausal women a 10-month oral hormone replacement therapy led to a significant increase of GH- and IGF I levels, however, the treated postmenopausal women did not reach the levels of the fertile controls. Those women who did not receive any hormonal treatment and the postmenopausal women before HRT showed nearly identical GH- and IGF I levels as well as somatometric-GH correlation patterns. CONCLUSIONS The results of the present paper indicate a marked influence of estrogens on GH and IGF I secretion. Furthermore, hormonal replacement therapy (HRT) may influence somatometric GH correlation patterns too.

Recombinant luteinizing hormone in ovarian hyperstimulation after stimulation failure in normogonadotropic women

The aim of this study was to examine the effect of an additional administration of recombinant luteinizing hormone (r-LH) to a gonadotropin-releasing hormone agonist (GnRHa) long protocol using recombinant follicle-stimulating hormone (r-FSH). In particular we determined whether such a stimulation protocol would be more effective in women (1) who respond poorly to stimulation with GnRHa long protocol using r-FSH only, and (2) whose LH concentrations after down-regulation in the cancelled cycle were low but above the values reported in the literature to be sufficient for folliculogenesis. After GnRHa desensitization 150 IU r-FSH and 75 IU r-LH were administered subcutaneously daily to six normogonadotropic women with low response to ovarian hyperstimulation using a GnRHa long protocol with r-FSH and low LH concentrations after down-regulation in the cancelled cycle. All six women had an oocyte retrieval and an embryo transfer after follicular stimulation. One women conceived but had a miscarriage in the eleventh week of gestation. Our results suggest that women with low response to a GnRHa long protocol with r-FSH, and whose LH concentration after down-regulation in the cancelled cycles were low, benefit from the additional administration of r-LH in a GnRHa long protocol using r-FSH. It seems that due to the additional administration of r-LH the LH concentration in the follicular phase is sufficient to support folliculogenesis.

Unexpected pregnancy during hormone-replacement therapy in a woman with elevated follicle-stimulating hormone levels and amenorrhea.

Pregnancy in patients with hypergonadotropic amenorrhea, although previously reported, remains quite rare. Women may conceive spontaneously or following different regimens of ovulation induction, thus indicating that ovarian failure is not always permanent. The case of an 18-year-old woman with premature ovarian failure, who conceived during hormone-replacement therapy, is reported. During hormone-replacement therapy, elevated gonadotropin levels returned to the physiologically normal range. It is suggested that this restored the receptors to luteinizing hormone and to follicle-stimulating hormone, which might have been downregulated. This hypothesis is supported by previous results from clinical trials and experimental work on a rat model.

Decreased maternal serum leptin in pregnancies complicated by preeclampsia

OBJECTIVE: To determine whether circulating levels of leptin differed between women with preeclampsia and women who had an uncomplicated pregnancy. METHODS: Maternal and umbilical venous plasma leptin concentrations obtained at delivery were compared in 36 pairs of women with either preeclampsia or normal pregnancy, matched 1:1 for prepregnancy body mass index and fetal gestational age at delivery. RESULTS: Prepregnancy body mass index was 21.1 ± 2.1 kg/m2 in either study group (range 17.6-25.3 kg/m2 and 17.7-25.3 kg/m2 in the normal and preeclamptic group, respectively). Mean fetal gestational age at delivery was 40.1 ± 1.3 weeks and 40.1 ± 1.2 weeks in the normal and preeclamptic group, respectively. Median leptin concentrations were significantly lower (p < .0001) in women with preeclampsia (8.3 ng/mL, range 3.5-20.0 ng/mL) than in normal pregnant women (20.2 ng/mL, range 6.0-63.7 ng/mL). Median umbilical venous leptin was not significantly different between groups (preeclampsia 11.8 ng/mL, range 2.0-37.2 ng/mL; normal 7.6 ng/mL, range 1.6-24.3 ng/mL; P =.377). Umbilical venous leptin levels correlated positively with birth weight in both groups (preeclampsia p = 0.501, P = .002; normal p = 0.517, P = .001), whereas no correlations were found between maternal and fetal hormone concentrations. Maternal leptin concentrations did not correlate with birth weight. CONCLUSION: Our data suggest that the correlation between umbilical venous leptin concentration and birth weight is independent of the presence of preeclampsia. Given the inconsistency in literature concerning circulating leptin levels in preeclampsia, further studies should investigate the regulatory systems of leptin in preeclampsia.

Serum leptin concentration in cord blood: relationship to birth weight and gender in pregnancies complicated by pre-eclampsia.

The aim of the study was to investigate cord blood leptin concentrations and their relationship to birth weight and gender in term pregnancies complicated by pre-eclampsia. Cord blood samples were obtained from 52 women, identified as having pre-eclampsia, and their newborns (31 males and 21 females) immediately after birth. Specimens were analyzed using a human leptin125 I radioimmunoassay. The relationship between leptin and anthropometrics was assessed by Spearman correlation. Differences in cord blood leptin levels between male and female infants were tested with the Mann- Whitney U test. The correlation between leptin and gender was computed using the productmoment-biseral correlation analysis for continuous and dichotomous variables. The multiple logistic regression analysis examined influences of sex, birth length, birth weight, birth weight/birth length ratio, ponderal index and maternal leptin as covariates on the fetal cord leptin level. Fetal leptin correlated positively with birth weight, length and weight/length ratio, in the total group and in the male subgroup and additionally with ponderal index in the female subgroup. Cord blood leptin concentrations in female newborns were significantly higher than in male newborns (p = 0.015), and concentrations correlated with gender (r =-0.315; p = 0.023). Multiple logistic regression analysis revealed four potential independent factors influencing fetal cord leptin: gender, birth weight, birth weight/birth length ratio and maternal leptin. In conclusion, cord leptin concentrations in pregnancies complicated by pre-eclampsia correlate positively with birth weight and gender. Leptin concentrations in female newborns are higher compared to male newborns.

Hormonal breast augmentation: prognostic relevance of insulin-like growth factor-I.

Many women would like to after their breasts but are deterred by the risks involved. Silicone breast implants have been linked to a variety of illnesses, the most controversial of which are connective-tissue diseases. These circumstances urged us to perform this pilot study using a non-invasive method that involved the application of 17 beta-estradiol as it is known that estradiol enhances expression of insulin-like growth factor-I (IGF-I) which can promote growth in breast tissue. Forty-five women were included in the study. Their breast volume, IGF-I, prolactin (PRL) and estradiol levels were measured before treatment and between each application of 80 mg estradiol polyphosphate. The womens satisfaction with the results obtained was also subsequently evaluated. In 21 women (46.7%), breast size increased from 824.3 +/- 13.7 mm to 898.5 +/- 12.5 mm after 6 months. In these women a significant increase in IGF-I values was noted after 4 weeks of treatment. The increase in IGF-I values was not statistically significant in the remaining women. In addition, treatment was not successful in these women. IGF-I concentration seems to be of prognostic value as far as the response of breast tissue to estrogen stimulation is concerned. If IGF-I levels do not increase within 1 month, treatment should be discontinued. If IGF-I values do increase, this indicates that treatment is likely to be successful and can therefore be continued.