High Serum Follicle-stimulating Hormone Levels Research Articles

SUN-239 A Case with Elevated Serum Follicle-Stimulating-Hormone (FSH) Concentrations Due to Macro-FSH

[Case report] A 64-year-old woman visited our hospital with the complaint of general malaise and anxiety lasting for two years. She had been diagnosed with idiopathic hypoparathyroidism because of hypocalcemia, hyperphosphatemia, low levels of intact PTH and calcification in the basal ganglia and was taking vitamin D and calcium phosphate. Endocrine workup disclosed high serum FSH [713mIU/mL (Elecsys), reference range for postmenopausal women: 10.5 - 142.8mIU/mL]. Other FSH assay platforms also showed high serum FSH levels: 523mIU/mL for Centaur and 457mIU/mL for Architect. Serum LH and E2 concentrations were 24.8mIU/mL and <11.8 pg/mL, respectively. Human anti-mouse antibody (HAMA) was not detected in the serum. [Methods] Large molecular weight FSH was precipitated using 12.5% polyethylene glycol (PEG) and the precipitation ratio (serum FSH - free FSH) / serum FSH was determined. The molecular size of FSH and IgG-bound FSH were examined using gel filtration chromatography (GFC) and protein G column (PG), respectively. Binding study was performed by incubating 125I-FSH (24000 cpm) with the serum and the specificity was examined by adding unlabeled FSH, LH, α-subunit of hCG, β-subunit of hCG and TSH. FSH was measured by enzyme immunoassay (EIA). We also examined these parameters in sera from 10 females with serum FSH>70 mIU/mL as controls. [Results] The dilution curve of the patient’s serum FSH was in parallel with that of reference one. The precipitation ratio by PEG was significantly elevated (95.4% vs. 20.3 ± 8.0% in controls). On GFC, a large proportion of serum FSH (89.4%) was eluted in the position of molecular weight > 150kDa, whereas FSH was mostly eluted at 36kDa in controls. Incubation of reference FSH (300mIU and 600mIU) with the serum (100µL) increased the peak levels of the large molecular weight FSH to be 84.0mIU/mL and 180.0 mIU/mL, respectively, from 21.6mIU/mL without exogenous FSH. Serum FSH bound to PG at a significantly higher ratio (87.3%) than that in controls (1.2 ± 1.4%). A significantly higher amount of 125I-FSH bound to the serum (5691 cpm) than that in controls (704 ± 170 cpm). The binding was displaced with an excess amount (600IU/mL) of unlabeled FSH to be 821 cpm (14.4%) and Scatchard analysis revealed the presence of anti-FSH autoantibodies (Ka 3.0 x 107 M-1, Bmax 0.92 x 10-8 M). The binding was slightly displaced by other hormones that shared α-subunit; 87.6% by LH, 90.4% by hCGα, 81.1% by hCGβ and 71.8% by TSH. [Conclusion] We report a woman with high serum FSH concentrations due to macro-FSH caused by anti-FSH autoantibodies. The possibility of macro-FSH should be considered in a case with unexpectedly high serum FSH concentrations.

Implications of diminished ovarian reserve (DOR) extend well beyond reproductive concerns

To investigate whether a diagnosis of diminished ovarian reserve (DOR) in premenopausal years has adverse implications for skeletal health and quality of life. This was a cross-sectional study of infertile, albeit healthy, mid-reproductive-age women (younger than 42 y) attending an academic infertility practice. Eighty-nine women with varying causes of infertility were prospectively enrolled. Serum (cycle d 1-3) was collected for markers of ovarian reserve, bone metabolism, testosterone, and free androgen index. Bone mineral density (BMD) was assessed and categorized as low if the Z score was less than -1.0). Infertile women with DOR (n = 28) demonstrated significantly higher serum follicle-stimulating hormone levels (P < 0.001), lower müllerian-inhibiting substance (MIS) levels (P < 0.001), smaller ovarian dimensions (P < 0.05), lower testosterone levels (P = 0.035), lower free androgen index (P = 0.019), and enhanced bone metabolism (P = 0.003); although the prevalence of low BMD was higher in women with DOR who were younger than 41, this relationship was not of statistical significance (P = 0.106). Women younger than 41 years of age with DOR were significantly more likely to manifest disturbed sleep (P = 0.049) and acknowledge dissatisfaction with sexual intimacy (P = 0.004) compared with those with infertility and normal ovarian reserve. After adjustment for potential confounders, a diagnosis of DOR was significantly associated with low BMD, increased bone turnover, sexual dissatisfaction, and disturbed sleep. Our data suggest that DOR unmasked in the context of infertility evaluation has adverse implications for a woman's well-being that extend well beyond the thus far appreciated reproductive concerns. A decline in ovarian hormones, specifically estrogen and testosterone, concomitant with DOR may be hypothesized as a mechanism that can explain the observed multisystem ramifications of DOR including increased bone turnover, low BMD, sexual distress, and disturbed sleep.

High frequency of Y chromosome microdeletions in idiopathic azoospermic men with high follicle-stimulating hormone levels

Y chromosome microdeletions were detected in 33.3% (6 out of 18) of idiopathic azoospermic patients with high serum follicle-stimulating hormone (FSH) levels in the present study. The results suggest that it may be necessary to detect microdeletions in patients with azoospermia, especially for those with high serum FSH levels, before assisted reproductive technology (ART) is provided to them.

Ovulation inducation and pregnancy despite estrogen deficiency and extremely high gonadotropins by lowering follicle stimulating hormone with ethinyl estradiol and using progesterone support in the luteal phase

Background: Spontaneous ovulations in women with hypergonadotropic hypogonadism are rare. Some cases of ovulation induction on a more consistent basis with treatment with ethinyl estradiol without gonadotropins have been reported. Objective: To determine if it is possible to induce ovulation and possibly achieve a pregnancy in a woman in premature ovarian failure who has had several serum follicle stimulating hormone (FSH) levels over 100 mIU/mL including one that was 164 mIU/mL by merely using ethinyl estradiol without gonadotropins. Materials and Methods: A 25 year old woman presented with oligomenorrhea over 2 years leading to amenorrhea with estrogen deficiency as manifested not only by serum estradiol <20 pg/mL but failure to have menses following progesterone withdrawal. Ethinyl estradiol 20–40 micrograms was used to lower serum FSH. Monitoring of follicle maturation was performed using sonography to determine follicle size and serum estradiol. Progesterone vaginal suppositories 200mg twice daily was used following demonstration of oocyte release from the follicle. No gonadotropins or clomiphene citrate was used. Results: Follicle maturation (as defined by a serum estradiol >200pg/mL and a dominant follicle >17 mm) and ovulation was achieved in 6 of 10 treatment cycles. A clinical pregnancy occurred in the ninth treatment cycle and an ongoing pregnancy past the first trimester wash achieved in cycle 10. In these 6 ovulatory cycles at least 1 (and usually 1) follicle of at least 18mm diameter was attained with the serum estradiol level >200 pg/mL. Conclusions: Despite small ovaries, amenorrhea, failure to have withdrawal menses following progesterone, absence of antral follicles on initial ultrasound and consistent extremely high serum FSH levels, ovulation and pregnancy was found to be possible by merely lowering the serum FSH. Possibly, the lowering of the FSH allows restoration of previous down-regulated FSH receptors allowing resumption of response to endogenous gonadotropins. This patient had been given an extremely poor prognosis by several previous consulting reproductive endocrinologists who would only treat her if she considered donor oocytes which was against her religious beliefs.

Using the male gamete for assisted reproduction: past, present, and future.

Using the male gamete for assisted reproduction: past, present, and future.

Low pulse oxygen saturation in post-menopausal women at high altitude is related to a high serum testosterone/estradiol ratio

Objective: The present study was designed to determine if low pulse oxygen saturation ( Sp o 2) in post-menopausal women at high altitude was related to high serum testosterone/estradiol (T/E 2) ratio. Method: Studies were carried out in 191 women living in Cerro de Pasco, Peru (4340 m above sea level) and in 56 women living in Lima (150 m asl). Body weight, height, Sp o 2, hematocrit, serum follicle stimulating hormone (FSH), T and E 2 levels were measured in all women. Body mass index (BMI), menopausal status and serum T/E 2 ratio were calculated from data. Result: At high altitude, the values of Sp o 2, serum T, and serum E 2 were significantly lower in post-menopausal than in pre-menopausal women. Hematocrit, serum FSH levels, and serum T/E 2 ratios were significantly higher in post-menopausal women. Serum T and E 2 levels, T/E 2 ratio, Sp o 2, and hematocrit levels were not further changed with time after menopause. Women with Sp o 2<85% had lower serum E 2, a higher serum T/E 2 ratio, and higher hematocrit values than women with Sp o 2>90%. At high altitude, multiple regression analysis showed that low Sp o 2 was related to menopausal status (−2.6±0.83; β±S.E.; P<0.002) and not to chronological age (−0.06±0.04; P: NS). Further analysis showed that low Sp o 2 was related to high basal serum FSH levels and a high serum T/E 2 ratio in the presence of an interaction between FSH and T/E 2. Conclusion: Low values of Sp o 2 in women at high altitude were related to a high T/E 2 ratio.

The effect of microsurgical varicocelectomy on serum follicle stimulating hormone, testosterone and free testosterone levels in infertile men with varicocele.

To analyse the effects of varicocelectomy on serum follicle-stimulating hormone (FSH), testosterone and free testosterone levels, and to investigate the interrelationships between seminal and hormonal variables. The records were retrospectively evaluated for 78 infertile patients who underwent microsurgical inguinal varicocelectomy, with documented serum FSH, testosterone, free testosterone levels, sperm concentration and sperm motility before and after surgery. Left and bilateral varicoceles were detected in 40 and 38 patients, respectively. In addition, serum hormonal values of 10 fertile men in whom physical examinations and Doppler ultrasonography revealed no evidence of varicocele were recorded and used as a control group. The mean (sd) serum FSH levels of all patients decreased from 15.21 (3.34) before surgery to 10.82 (2.93) mIU/mL afterward (P=0.01), and serum testosterone levels increased from 5.63 (1.40) to 8.37 (2.2) ng/mL (P=0.01), whereas free testosterone levels increased from 23.13 (3.19) to 32.83 (4.37) pg/mL (P<0.001). In contrast to the significant difference in sperm motility before and after surgery of all patients (P<0.01), the difference in sperm count was insignificant (P>0.05). Thirty-six patients with high serum FSH levels before surgery had significantly lower levels afterward (P=0.001). In this group, the sperm concentration and motility also increased, from 17.66 (4.35) to 20.76 (4.37) million/mL (P=0.05) and from 30.9 (4.4)% to 37.5 (4.34)%, respectively (P=0.01). In the remaining 42 patients who had normal preoperative serum FSH levels, there was a slight decrease after surgery (P=0.02). Their sperm concentration increased slightly (P=0. 04), and motility also increased (P=0.001). Sixty patients had a significantly higher testosterone level after surgery; in this group the sperm concentration and motility increased (P=0.01). Varicocelectomy promotes Sertoli and Leydig cell function. The significant increase in serum free testosterone level results in a significant improvement in sperm concentration and motility.

Progress and Therapy of Stress Amenorrhea

Thirty-two patients with stress amenorrhea of less than 1 years duration were found to have withdrawal bleeding after progestin administration, normal serum follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels, and good responsiveness to LH-releasing hormone (LH-RH); ovulation was induced following the admininstration of clomiphene citrate. On the other hand, in 11 of 14 patients with stress amenorrhea of longer than 1 years duration, no bleeding followed the administration of progestin, and there were noted high serum FSH and LH levels, exaggerated release responsiveness to LH-RH, and atrophic vaginal smears and endometrium. In addition, it was difficult to induce ovulation by various treatments. The findings suggest that dysfunction in the hypothalamic cyclic (not tonic) center regulating ovulation was the originating factor in the amenorrhea in question and that ovulation should be induced at least once yearly to prevent ovarian function from declining in this type of anovulatory state existing for more than 1 year.

Reactive Pituitary Abnormalities in Patients With Klinefelter's and Turner's Syndromes

Ten unselected patients with gonadal dysgenesis, three with Klinefelter's and seven with Turner's syndromes, were studied. Two of the patients with Klinefelter's and two with Turner's syndromes had enlarged pituitary fossae. The other six patients had normal sized sella, but showed localized change in the sellar contour on polytomography, suggesting hyperplasia or microadenoma formation of the pituitary gland. All ten patients had abnormally high serum follicle-stimulating hormone levels both at basal and after luteinizing hormone-releasing hormone stimulation. These results suggest that hyperplasia or microadenoma of the pituitary gland may occur secondary to gonadal failure, producing enlarged volume or attenuation in the normal contour of the sella turcica. Lack of awareness of reactive pituitary changes secondary to gonadal failure may result in inappropriate surgical management of what may appear to be primary pituitary tumor.

Pituitary-ovarian function in breast cancer patients on adjuvant chemoimmunotherapy

One hundred thirty-one patients with operable breast cancer were treated with adjuvant chemoimmunotherapy consisting of 5-fluorouracil, adriamycin, cyclophosphamide, and BCG (FAC-BCG). Fifty-five of 131 patients were premenopausal of which 71% (38/55) became amenorrheic. To determine the mechanism of amenorrhea, we measured the immunoreactive serum luteinizing hormone (LH) and follicle-stimulating hormone (FSH), and plasma estradiol (E2) before and after intravenous administration of luteinizing hormone-releasing hormone (LH-RH) in 11 unselected premenopausal patients who developed amenorrhea and 11 unselected patients who did not. Serum prolactin (PRL) levels were also measured before and after iv administration of thyrotropin-releasing hormone (TRH). Our results showed that patients who developed amenorrhea had abnormally high serum LH and FSH levels at basal and after LH-RH stimulation and low plasma estradiol. Serum PRL levels were normal. Patients who developed amenorrhea were older than those who did not, but their serum LH and FSH levels were also significantly higher and plasma estrogens were significantly lower than that found in 11 normal women with regular menses of the same age range. These results indicate that amenorrhea that develops in some patients with breast cancer after FAC-BCG therapy is a result of primary ovarian failure.

PITUITARY-GONADAL RELATIONS IN FEMALE CHILDREN AND ADOLESCENTS

Extract: Data are provided which concern daytime levels of circulating follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estradiol and progesterone in healthy female children and adolescents. These findings are correlated with sexual and skeletal maturation. Serum estradiol and testosterone levels were low in childhood, but rose to adult levels coincident with the appearance of secondary sexual characteristics. Serum LH levels did not rise above prepubertal levels until these characteristics were already apparent. Serum FSH levels showed a biphasic pattern with age; widely scattered values, some into the adult range, were seen in infancy. Mean FSH levels then declined throughout childhood until the onset of clinical puberty at which time they increased again to adult levels. Serum progesterone concentrations remained low (below 150 ng/100 ml) until menarche. Levels of serum progresterone which suggested possible ovulation and corpus luteum formation (over 200 ng/100 ml) were found in 9 of 30 girls who were less than 3 years postmenarchal. Speculation: The finding of high serum FSH levels in female, but not in male, infants suggests that the infantile ovary may be relatively resistant to FSH stimulation. The decline in FSH levels during early childhood may represent increasing ovarian maturation, at least in terms of ability to secrete as yet unidentified gonadotropin-inhibiting feedback substance (or substances). The onset of female puberty appears to be heralded by increasing FSH secretion; although nocturnal LH release may be characteristic of early puberty, daytime elevation of this hormone is not seen until midpuberty. The surprising finding of luteal range serum progesterone levels in many early postmenarchal girls suggests that anovulatory cycles may not be characteristic of these years. The reported relative infertility of adolescent girls may relate to factors other than ovulation (such as a short corpus luteum life-span, defects in sperm capacitation, or impaired blastocyst implantation).

Pituitary-gonadal relations in female children and adolescents.

Extract: Data are provided which concern daytime levels of circulating follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estradiol and progesterone in healthy female children and adolescents. These findings are correlated with sexual and skeletal maturation. Serum estradiol and testosterone levels were low in childhood, but rose to adult levels coincident with the appearance of secondary sexual characteristics. Serum LH levels did not rise above prepubertal levels until these characteristics were already apparent. Serum FSH levels showed a biphasic pattern with age; widely scattered values, some into the adult range, were seen in infancy. Mean FSH levels then declined throughout childhood until the onset of clinical puberty at which time they increased again to adult levels. Serum progesterone concentrations remained low (below 150 ng/100 ml) until menarche. Levels of serum progresterone which suggested possible ovulation and corpus luteum formation (over 200 ng/100 ml) were found in 9 of 30 girls who were less than 3 years postmenarchal.Speculation: The finding of high serum FSH levels in female, but not in male, infants suggests that the infantile ovary may be relatively resistant to FSH stimulation. The decline in FSH levels during early childhood may represent increasing ovarian maturation, at least in terms of ability to secrete as yet unidentified gonadotropin-inhibiting feedback substance (or substances). The onset of female puberty appears to be heralded by increasing FSH secretion; although nocturnal LH release may be characteristic of early puberty, daytime elevation of this hormone is not seen until midpuberty. The surprising finding of luteal range serum progesterone levels in many early postmenarchal girls suggests that anovulatory cycles may not be characteristic of these years. The reported relative infertility of adolescent girls may relate to factors other than ovulation (such as a short corpus luteum life-span, defects in sperm capacitation, or impaired blastocyst implantation).