Normal Spontaneous Premature Ovarian Failure Research Articles

Factors associated with bone density in young women with karyotypically normal spontaneous premature ovarian failure

To evaluate bone density and associated factors in women with premature ovarian failure (POF) compared to age-matched women with normal ovarian function. A cross-sectional study of 50 patients with POF undergoing bone mineral densitometry was conducted, compared to 50 women paired by age who menstruated regularly. In women with POF, the mean bone mineral density measured was 1.22 g/cm(2) at the spine and 0.92 g/cm(2) at the femur, values which were significantly lower than in the control group (P < 0.0001). Factors directly associated with bone density of the lumbar spine were age and with bone density of the femur were BMI and reproductive age. Young women with POF have a decrease in lumbar spine and femoral bone density. Age, reproductive age and BMI were the factors associated with BMD. These women need early investigation and treatment to prevent bone loss and minimize fracture risk in the future.

Bone loss in young women with premature ovarian failure

To evaluate the effect of premature ovarian failure on bone mineral density. Forty-five women with karyotypically normal spontaneous premature ovarian failure underwent hip and spinal bone density measurements by dual energy X-ray absorptiometry. Findings were compared with a control group of 61 women of similar age. The median (range) age of the women with premature ovarian failure was 33 (18-39) years. The median (range) time since diagnosis of premature ovarian failure was 2 years (0.5-7). Forty-one of the women (91%) had sought medical advice previously and had taken a variety of estrogen and progestin replacement regimens at least intermittently. Both the femoral neck bone mineral density measurements and the spinal bone mineral density measurements were significantly lower than measurements of the control group (P < 0.05). Our study shows that premature ovarian failure has significantly lower levels of bone mineral density than the control group of normal women. We suggest that hormone replacement therapy should be substituted early and consistently in affected patients. Our data also raise questions about whether preservation of bone mass in these patients will require replacement of additional gonadal steroids.

The clinical significance of antenatal detection of discordant umbilical arteries

To evaluate the effects of karotypically normal spontaneous premature ovarian failure on femoral neck bone mineral density. Eighty-nine women with karyotypically normal spontaneous premature ovarian failure who desired fertility were evaluated at a tertiary care academic center and underwent hip and spinal bone density measurements by conventional dual-photon absorptiometry. Seventy-seven of the women (87%) had sought medical advice previously and had taken a variety of estrogen and progestin replacement regimens at least intermittently. The median (range) age was 32 (20-39) years, and the median (range) time since diagnosis was 1.5 (0.5-11) years. Findings were compared with a reference group of 218 regularly menstruating women of similar age. Sixty of the 89 women with premature ovarian failure (67%, 95% confidence interval 57, 77) had a femoral neck bone mineral density more than 1 standard deviation (SD) below the mean of the reference group (P < .001, chi2 with Yates correction). Even in women in whom the bone mineral density measurement was made within just 1.5 years of the diagnosis, nearly one-half (47%) had a femoral neck bone mineral density more than 1 SD below the mean of the reference group (P < .01). Two-thirds of young women with karyotypically normal spontaneous premature ovarian failure have a femoral neck bone mineral density more than 1 SD below the mean of a reference group. These young women need early education regarding strategies to maintain their bone mass and ongoing medical evaluation to maintain compliance with these strategies.

Bone loss in young women with karyotypically normal spontaneous premature ovarian failure

To compare monochorionic and dichorionic pregnancies for intertwin disparities in fetal size. Monochorionic and dichorionic pregnancies, recruited from an ultrasound screening study at 10-14 weeks' gestation, were compared for intertwin disparities in crown-rump length and birth weight. The disparities were expressed as a percentage of the values of the larger twin. The study population was 123 monochorionic and 416 dichorionic twin pregnancies. In the 104 monochorionic and 381 dichorionic pregnancies resulting in two live births, there were no significant differences in median (range) intertwin disparity in crown-rump length (4.3% [0-18.8%] and 3.4% [0-25.5%]) or birth weight (10.2% [0-37.0%] and 9.3% [0-49.2%]). To determine that the observed 0.9% intertwin differences in crown-rump length and birth weight between the two groups were significant at alpha = .05 with 80% power, we would have had to examine a minimum of 984 and 926 twin pregnancies, respectively, assuming that the proportion of monochorionic to dichorionic twins remained the same as in the current study. In addition, there was no significant correlation between intertwin disparities in crown-rump length and intertwin disparities in birth weight in either the monochorionic (P = .40, Rho = 0.02, 95% confidence interval [CI] -0.17, 0.22) or dichorionic group (P = .44, Rho = 0.01, 95% CI -0.11, 0.09). The median (range) intertwin disparity in crown-rump length in 15 dichorionic pregnancies with chromosomally abnormal fetuses (6.6% [0-24.0%]) and in 20 dichorionic pregnancies that ended in miscarriage or intrauterine death of one or both fetuses (7.7% [0-43.9%]) was significantly higher than in dichorionic pregnancies resulting in two live births (Z = 2.49 and 3.26, respectively, and P = .01 and .001, respectively). However, in 19 monochorionic twins with adverse pregnancy outcome there was no significant difference in median (range) intertwin disparity in crown-rump length (4.5% [0-20.0%]) from monochorionic pregnancies resulting in two live births (4.3% [0-18.8%]). To determine that the observed 0.2% difference in intertwin difference in crown-rump length between the two groups was significant at alpha = .05 with 80% power we would have had to examine a minimum of 5652 monochorionic twin pregnancies, assuming that the proportion in each group remained the same as in the current study. The findings of this study demonstrate that monochorionic and dichorionic twin pregnancies do not differ significantly in intertwin disparity in fetal size, either in early pregnancy or at birth.

Routine endocrine screening for patients with karyotypically normal spontaneous premature ovarian failure

To evaluate the usefulness of routine screening for other associated autoimmune endocrine disorders in patients with karyotypically normal spontaneous premature ovarian failure. One hundred nineteen women with karyotypically normal spontaneous premature ovarian failure (FSH exceeding 40 mIU/mL) who desired fertility were evaluated at a tertiary care academic center by physical examination, measurement of serum free thyroxine and TSH, ACTH stimulation test, fasting serum glucose, 3-hour glucose tolerance test, measurement of serum electrolytes including total calcium, and measurement of serum vitamin B12. Twenty-two of 119 patients (18.5%) were known to have hypothyroidism and three were known to have Addison disease. Ten new cases of hypothyroidism and three new cases of diabetes mellitus were discovered. However, no new cases of adrenal insufficiency, hypoparathyroidism, or pernicious anemia were found. Screening for hypothyroidism and diabetes appears justified in those patients with karyotypically normal spontaneous premature ovarian failure who desire fertility. However, our findings suggest that in these patients, testing for other associated autoimmune endocrine disorders may be reserved for those with clinical indications.

Development of luteinized graafian follicles in patients with karyotypically normal spontaneous premature ovarian failure.

Despite having amenorrhea and markedly elevated serum gonadotropin levels, some women with karyotypically normal spontaneous premature ovarian failure, nevertheless, have ovarian follicles that function intermittently. Graafian follicles capable of responding to these high FSH levels are faced with high serum LH levels as well, which might induce inappropriate luteinization and prevent normal follicle function. We examined this possibility using weekly blood sampling and sonography in 65 patients. Nearly 50% of our patients demonstrated ovarian follicle function [serum estradiol, > 183 pmol/L (50 pg/mL)] during a median of 4 months of observation (range, 2-6 months). However, during this observation, only 16% achieved an ovulatory serum progesterone level [> 9.5 nmol/L (3.0 ng/mL)]. We imaged an antral follicle by sonography in over 40% of patients (27 of 65), and serum estradiol was significantly greater when an antral follicle was present. The follicles in these patients were not functioning normally, however. In contrast to normal women, patients with ovarian failure had poor correlation between follicle diameter and serum estradiol. We biopsied these antral follicles in 6 patients and found luteinized Graafian follicles in all cases. Therefore, luteinized Graafian follicles account for at least 60% of the antral structures imaged (95% confidence limit). Thus, inappropriate luteinization of Graafian follicles appears to be a major pathophysiological mechanism in patients with karyotypically normal spontaneous premature ovarian failure.

Development of luteinized graafian follicles in patients with karyotypically normal spontaneous premature ovarian failure

Development of luteinized graafian follicles in patients with karyotypically normal spontaneous premature ovarian failure

A controlled study of danazol for the treatment of karyotypically normal spontaneous premature ovarian failure

To determine if the immunomodulatory and gonadotropin-suppressing properties of danazol would improve follicle function or ovulation rates in patients with karyotypically normal spontaneous premature ovarian failure. Prospective, double-blind, crossover trial. Tertiary care research institution. Two intervention phases lasting 4 months each: one phase during which patients received a standardized estrogen and progestin replacement regimen and one phase during which each patient received a twice daily 400 mg oral dose of danazol. Fifty-two patients with karyotypically normal spontaneous premature ovarian failure ranging in age from 21 to 39 years. We measured serum E2 and P levels weekly during the 2 months after each intervention. We defined a serum E2 > 50 pg/mL (184 pmol/L) as evidence of ovarian follicle function and a P > 3.0 ng/mL (9.5 nmol/L) as evidence for ovulation. Of the 46 patients who completed the study, danazol did not significantly enhance ovarian follicle function or the chance of ovulation. Eight patients ovulated after danazol and four patients ovulated after estrogen and progestin. The power to detect a 30% and a 5% ovulation success rate with therapy was 0.80 and 0.90, respectively. Overall, 30 of 46 women (65%) demonstrated ovarian follicle function and 10 women (21%) ovulated. We were unable to demonstrate a statistically significant benefit from the immunomodulatory and gonadotropin-suppressing effects of danazol in patients with karyotypically normal spontaneous premature ovarian failure. These patients often have spontaneous remission. Thus, controlled studies are required to determine the effectiveness of treatments for this condition.

Karyotypically normal spontaneous premature ovarian failure: evaluation of association with the class II major histocompatibility complex.

Patients with premature ovarian failure (POF) have been reported to have an increased frequency of the major histocompatibility class (MHC) class II antigen HLA-DR3. Here we attempt to confirm this association. We performed MHC class II immunophenotyping of HLA-DR antigens 1-10 on 102 North American caucasians with confirmed POF and 102 control caucasian women. All patients had experienced amenorrhea before the age of 40 yr and had elevated serum gonadotropins on repeated study. We found no significant increase in HLA-DR3 frequency in patients with POF when compared to our control group (P = 0.52) or even when compared to a large reference population (n = 1927) that did not differ significantly from our control group (P = 0.47). Our patients did have an increased frequency of HLA DR4 compared to this large reference population (41% vs. 23%; P < 0.001), but we were unable to demonstrate increased HLA DR4 frequency using our control group (31%; P = 0.14). In conclusion, despite a power of 99%, we were unable to confirm a significant increase in MHC class II HLA-DR3 frequency in patients with POF.

Karyotypically normal spontaneous premature ovarian failure: evaluation of association with the class II major histocompatibility complex

Karyotypically normal spontaneous premature ovarian failure: evaluation of association with the class II major histocompatibility complex

Gonadotropin suppression for the treatment of karyotypically normal spontaneous premature ovarian failure: a controlled trial

To determine if gonadotropin suppression improves ovarian follicle function or ovulation rates in patients with karyotypically normal spontaneous premature ovarian failure. Prospective, double-blind, placebo-controlled, crossover trial. Tertiary care research institution. Two intervention phases lasting 4 months each: one placebo phase, and one treatment phase during which each patient received daily subcutaneous injections of 300 micrograms of the gonadotropin-releasing hormone agonist (GnRH-a) deslorelin. During both phases, patients took a standardized estrogen (E) replacement regimen. Twenty-six patients with karyotypically normal spontaneous premature ovarian failure ranging in age from 18 to 39 years. We measured serum estradiol (E2) and progesterone (P) levels weekly during the 2 months after each intervention. We defined a serum E2 greater than 50 pg/mL (184 pmol/L) as evidence for ovarian follicle function and a serum P greater than 3.0 ng/mL (9.5 nmol/L) as evidence for ovulation. The GnRH-a therapy did not significantly enhance recovery of ovarian follicle function or the chance of ovulation. The power to detect a 40% and a 33% ovulation success rate with therapy was 0.95 and 0.83, respectively. We found evidence for ovarian follicle function in 11 of 23 women (48%), and 4 women (17%) ovulated. Patients with karyotypically normal spontaneous premature ovarian failure treated with E replacement did not benefit from the additional gonadotropin suppression achieved with GnRH-a. Because these patients have a significant possibility of spontaneous remission, attempts to induce ovulation should be limited to controlled trials designed to determine safety and effectiveness.

Increased peripheral T lymphocyte activation in patients with karyotypically normal spontaneous premature ovarian failure

To determine if soluble interleukin 2 (IL-2) receptor measured in serum by an enzyme-linked immunosorbent assay (ELISA) might be useful in managing patients with karyotypically normal spontaneous premature ovarian failure. Prospective, controlled observation. Tertiary care research institution. None. Twenty-four patients with karyotypically normal spontaneous premature ovarian failure comprised the study group. Forty-two healthy men and women comprised the normal reference group. We measured peripheral T lymphocyte human leukocyte antigen locus-DR (HLA-DR) expression and IL-2 receptor expression using monoclonal antibodies and flow cytometry. We measured soluble IL-2 receptor levels in serum using an ELISA. Consistent with previous findings, our patients had significantly higher HLA-DR expression on peripheral T lymphocytes (5.3 +/- 0.46) as compared with controls (3.5 +/- 0.34) (mean +/- SEM, P less than 0.01). Seven patients also had elevated IL-2 receptor expression on peripheral T lymphocytes (P less than 0.05). However, soluble IL-2 receptor levels in the serum did not differ significantly from normals. Patients with karyotypically normal spontaneous premature ovarian failure have a modest increase in peripheral T lymphocyte activation measured by flow cytometry. This degree of activation does not result in increased soluble IL-2 receptor release measured by ELISA.