Premature ovarian insufficiency (POI) is defined as a primary ovarian defect characterized by absent menarche (primary amenorrhea) or premature depletion of ovarian follicles before the age of 40 (secondary amenorrhea) with hypergonadotropism and hypoestrogenism.We studied the clinical, biological, and genetic data related to 50 POI patients with a mean age of menopause of 29 years (94% with secondary amenorrhea, 6% with primary amenorrhea and 15% with a family history of POI). Seventeen patients were affected by endocrine autoimmune diseases, antral follicles were observed in 31 patients by ultrasonography.Karyotype analysis did not show any abnormality of the X chromosome. No mutation in FSH receptor and GDF-9 genes was reported, while in one patient a variant of BMP-15 gene (A180T) was found. Four patients had fragile X mental retardation 1 gene (FMR1) premutation and one an intermediate sized CGG repeats of the same gene. Two patients with FMR1 premutation were sister and developed secondary amenorrhea at the age of 34 and 37 years. The other two patients presented with oligoamenorrhea at the age of 39 and 34 years. The patient harboured the intermediate sized CGG repeats developed secondary amenorrhea at the age of 33 years.The genetic analysis performed on a cohort of patients with POI revealed that 8% had FMR1 premutation and only one patient a previously known variant of BMP-15 gene. No alteration of the karyotype and FSH receptor and GDF-9 genes was evidenced.

A 33-year-old woman presented to an endocrinology clinic with a 5-year history of secondary amenorrhea. 2 years before presentation, she had noticed progressively worsening signs of virilization.Measurement of levels of serum free and total testosterone, androstenedione, dehydroepiandrosterone sulfate and gonadotropins; transvaginal ultrasonography, abdominal and pelvic MRI and (18)F-fluorodeoxyglucose PET imaging.Virilization secondary to an ovarian Leydig cell tumor.The patient underwent a left salpingo-oophorectomy that confirmed the diagnosis of a unilateral Leydig cell tumor. Complete normalization of androgens and gonadotropin levels was achieved after surgery.

A case of POF in a 31-year-old woman with karyotype 47,XXX. The aim of the study was to discuss a case of POF in a 31-year-old patient with polysomy 47,XXX. The described karyotype is not usually associated with this characteristic physical phenotype. In some rare cases, menstrual disorders, sterility, secondary amenorrhoea, premature menopause, and low intelligence are found. Our observations revealed the necessity for cytogenetic examination in all women at reproductive age with symptoms of premature ovarian failure. According to the data found in literature, patients with POF and karyotype disorders belong to the risk group of premature death, mostly for cardiological reasons. Raising patient awareness about the risk may have a positive effect on quality of life and regularity of check-ups.

Osteoporosis is uncommon in premenopausal women, and most cases have a secondary cause. Women with osteoporosis and no known secondary cause are said to have idiopathic osteoporosis (IOP). We aimed to estimate the proportion of premenopausal women seen in our referral center with IOP as opposed to secondary osteoporosis, to describe their clinical characteristics, to compare women with a low-trauma fracture history with those with low bone mineral density (BMD) alone, and to estimate the frequency of bisphosphonate use.We reviewed medical records from all premenopausal women evaluated for osteoporosis or low BMD in our center during 2005. We included premenopausal women diagnosed on the basis of low-trauma fracture, low BMD or both (Z score < or= -2.0 or T score < or = -2.5), or both.Among these patients (n = 61; mean age 37 +/- 8), 57 (93%) were Caucasian, 34 (57%) had a family history of osteoporosis, and 26 (43%) had used bisphosphonates. The most common secondary causes were amenorrhea (34%, n = 21), anorexia nervosa (16%, n = 10), and glucocorticoid exposure (13%, n = 8). After exclusion of secondary causes, 39% (24 of 61) of the entire group and 48% (14 of 29) of the fracture group were thought to have IOP. Women with a known secondary cause had lower BMD Z scores at the spine and hip than those with IOP. Women with low BMD and no fractures had shorter stature and weighed less than those with fractures, but overall differences between the groups were not statistically significant. Bisphosphonates had been prescribed for 38% (11 of 29) of women with a fracture history and 47% (15 of 32) of women with low BMD and no fractures.Our findings suggest that IOP is common among premenopausal women with osteoporosis or low BMD evaluated at a referral center. The smaller stature of women diagnosed only on the basis of BMD criteria raises the question of whether their areal BMD measurements are spuriously low because of smaller bone size. The high proportion of premenopausal women who had been prescribed oral bisphosphonates for low BMD measurements is of concern, as such women are likely to be at low short-term risk of fracture, and a more conservative approach to therapy is preferable in this group.

Nodular thyroid disease and osteoporosis share some common factors such as: 1) elevated frequency in the general population; 2) major prevalence in the female sex; 2) incidence proportional to the age. There is a wide debate in literature regarding the real impact of chronic treatment with L-thyroxin (LT4) on the bone mineral density (BMD), especially in post-menopausal women. The aim of this study was to undertake to evaluate the effects of LT4 administration for the treatment of normo-functioning nodular thyroid disease on the BMD in post-menopausal women after one year of continuative treatment. Particular attention was paid in examining the role of some anamnestic risk factors for osteoporosis on the clinical response.Ninety nine postmenopausal women of age comprised between 50 and 56 years were examined before and after 1 year of therapy with a fixed dose of LT4 for the treatment of nodular thyroid disease by monitoring the following laboratory parameters: thyroid stimulating hormone (TSH), FT4, FT3, antithyroglobulin antibodies [AbTG], hyroid peroxidase antibodies [AbTPO], serum calcium and alkaline phosphatase levels and 24-urinary excretion of calcium and hydroxyproline. Bone mineral density (BMD) was measured by dual X-ray absorptiometry of the lumbar vertebrae.The results of this study showed that the patients on treatment with LT4 have a slight, but significant reduction of the BMD after 1 year of treatment, associated with increased serum levels of alkaline phosphatase and urinary excretion of hydroxyproline. Comparison between patients with unsuppressed (group A) or suppressed (group B) TSH following LT4 treatment showed that group B patients had significantly lower BMD. The following risk factors influenced, in a statistically significant manner, the BMD: 1) Body Mass Index <19 kg/m(2); 2) the onset of menarche after the age of 15 years; 3) history positive for period of amenorrhoea; 4) nulliparity; 5) surgical menopause; 6) lack of hormonal replacement therapy; and 7) presence of auto-antibodies against thyroid antigens.LT4 treatment in postmenopausal women reduced significantly the BMD. This treatment should be therefore prescribed with caution in this condition and particularly when the following risk factors are present: surgically driven menopause, constitutional thinness, history of nulliparity, absence of hormonal treatment, positive history of secondary amenorrhoea during the reproductive age, autoimmune thyroid disease and delayed menarche.

To determine if ovulation and pregnancy could be achieved in a case of amenorrhea, estrogen deficiency, and markedly elevated serum follicle stimulating hormone (FSH) through reduction of the serum FSH by a gonadotropin releasing hormone antagonist.A 37-year-old woman with hypergonadotropic secondary amenorrhea related to two courses of chemotherapy with alkylating agents and abdominal radiation therapy (Hodgkin's disease and breast cancer) was treated with cetrorelix in an attempt to induce ovulation by lowering elevated serum FSH and hopefully restore sensitivity of the few remaining follicles by restoring down-regulated FSH receptors. She was monitored with serum estradiol (E2), FSH, luteinizing hormone (LH), progesterone (P) levels and sonography.As the serum FSH dropped the serum E2 rose and peaked at 200 pg/ml after ten days of cetrotide. She conceived in that cycle. A viable ongoing pregnancy with appropriate ultrasound findings was demonstrated 40 days from conception.This is the first case description of successful ovulation and pregnancy following induction of ovulation with the GnRH antagonist cetrorelix. The possibility exists that the ovulation was spontaneous but it seems unlikely. It has been estimated that the chance of spontaneous ovulation and pregnancy in cases of premature ovarian failure is 1:9,200.