Fragile X premutation is a significant risk factor for premature ovarian failure: the International Collaborative POF in Fragile X study--preliminary data. (25/1799)

The preliminary results of an international collaborative study examining premature menopause in fragile X carriers are presented. A total of 760 women from fragile X families was surveyed about their fragile X carrier status and their menstrual and reproductive histories. Among the subjects, 395 carried a premutation, 128 carried a full mutation, and 237 were noncarriers. Sixty-three (16%) of the premutation carriers had experienced menopause prior to the age of 40 compared with none of the full mutation carriers and one (0.4%) of the controls. Based on these preliminary data, there is a significant association between fragile X premutation carrier status and premature menopause.  (+info)

Clinical outcome after unilateral oophorectomy in patients with polycystic ovary syndrome. (26/1799)

The objective of this study is to report retrospectively on the clinical outcome of unilateral oophorectomy in 14 women with polycystic ovary syndrome who had undergone this treatment 14-18 years ago in our hospital for clomiphene citrate-resistant anovulation and long standing infertility or for severe hirsutism. The main outcome measures were menstrual cycle, pregnancy, hirsutism, testosterone concentrations, and premature ovarian failure. Unilateral oophorectomy restored regular menstrual cycles in 12 of the 14 patients. Thirteen years later, nine out of 12 patients still had regular menstrual cycles. Ten patients wished to become pregnant. Seven of them conceived spontaneously. Eleven patients complained of severe hirsutism. After unilateral oophorectomy, hirsutism regressed subjectively in six. Testosterone blood concentrations decreased significantly within the first year after unilateral oophorectomy in 11 patients. None of the women entered menopause within 14-18 years after surgery. Our results indicate that unilateral oophorectomy restores ovulatory function for many years in the majority of patients and does not result in premature ovarian failure. However, unilateral oophorectomy should not be recommended as a standard treatment for clomiphene citrate-resistant patients with polycystic ovary syndrome.  (+info)

Bioactivity of prolactin isoforms: lactation and recovery of menses in nursing women. (27/1799)

To assess whether plasma prolactin (PRL) characteristics relate to lactogenesis and absence or presence of menstrual cycles, we measured bioactive PRL (BIO-PRL) using the Nb2 assay, immunoreactive PRL (IR-PRL) by radio-immunoassay, calculated equations describing the BIO-PRL-IR-PRL relationship and separated charged PRL isoforms (by chromatofocusing) in five amenorrhoeic and five cycling nursing women at 6 months postpartum and in 10 cycling non-nursing women. Plasma samples were drawn before and 30 min after a suckling episode at 0800, 1600 and 2400 h in nursing women and at the same hours in non-nursing women. BIO-PRL and IR-PRL concentrations were highest in amenorrhoeic nursing women, intermediate in cycling nursing women and lowest in cycling non-nursing women. The BIO-PRL-IR-PRL relationship shows that a given amount of IR-PRL corresponds to equivalent amounts of BIO-PRL in cycling nursing and cycling non-nursing women, and to a larger extent in amenorrhoeic nursing women. IR-PRL was present in plasma as several charge isoforms. Bioactive isoforms eluting at pH 6.0-5.1 were found in amenorrhoeic and cycling nursing women, reaching similar concentrations after suckling. Bioactive isoforms eluting at pH 7.0-6.1 were found only in amenorrhoeic nursing women. We speculate that isoforms eluting at pH 6.0-5.1 may play a role in lactation and isoforms eluting at pH 7.0-6.1, in lactational amenorrhoea.  (+info)

Leptin concentrations in normal women following bilateral ovariectomy. (28/1799)

To study the relationships between gonadal steroids and leptin, 20 women with normal cycles were investigated during the postoperative period following a laparotomy. Fourteen women underwent bilateral ovariectomy plus total hysterectomy either in the mid- to late follicular phase (n = 7, group 1) or in the early to midluteal phase (n = 7, group 2). The remaining six of the 20 women underwent cholocystectomy in the early to midfollicular phase of the cycle and were used as controls (group 3). In all three groups, serum leptin values decreased rapidly up to post-operative day 4. Then, leptin values increased significantly only in group 3 (P < 0.05). Leptin values before and after the operation showed significant positive correlations with body mass index (BMI), oestradiol and progesterone. However, with multiple regression analysis, BMI was the only parameter significantly correlated with leptin in group 3 (days 0 and 4-7), whereas in groups 1 and 2 progesterone and BMI showed independent significant correlations with leptin (days 0 and 8, r = 0.601 and r = 0.602 respectively). These results demonstrate for the first time a significant reduction in leptin concentrations in normal women following bilateral ovariectomy. Although BMI seems to be the predominant factor, it is also suggested that oestradiol and progesterone may participate in the control of leptin production during the human menstrual cycle.  (+info)

Vascular smooth muscle cell proliferation in arterioles of the human endometrium. (29/1799)

Menorrhagia affects approximately 15% of all women, often without identifiable cause. Endometrial spiral arterioles are believed to play a major role in controlling menstruation, and are a major site of menstrual loss. We postulate that alterations in the growth and development of spiral arterioles, particularly the vascular smooth muscle cells (VSMC), may contribute to menorrhagia. We examined VSMC proliferation around endometrial arterioles in control and menorrhagic tissues and the possible roles of transforming growth factor beta (TGF-beta) and endothelin in this process. Proliferating VSMC were located immuno-histochemically, then evaluated using computer-aided image analysis. VSMC proliferation was low and constant during the early stages of the menstrual cycle, increasing at the mid to late secretory stages (P < 0.002). Menorrhagic women had significantly reduced VSMC proliferation in their spiral arterioles at the mid and late secretory stages (P < 0.02). VSMC around straight arterioles proliferated at similar rates across the cycle, apart from a significant decrease in VSMC proliferation in menorrhagic women at the late secretory stage (P < 0.002). Endothelin concentrations decreased significantly in the epithelium of menorrhagic women (P = 0.05), while TGF-beta demonstrated no significant differences in the mid to late secretory tissues studied. The results indicate a significant functional difference between the spiral arterioles of control and menorrhagic women that may play a role in menorrhagia, while leaving the roles of endothelin and TGF-beta undetermined.  (+info)

Endometrial pinopodes indicate a shift in the window of receptivity in IVF cycles. (30/1799)

The formation of endometrial pinopodes detected by scanning electron microscopy may be a specific marker for uterine receptivity. Aiming to assess the effects of ovarian stimulation on pinopode formation, we examined sequential endometrial biopsies from 17 oocyte donors. Seven normally menstruating women served as controls. Up to four samples were taken from each woman at 24-72 h intervals between days 14 and 24, giving a total of 69 samples. The day of oocyte retrieval was designated day 14 in ovarian stimulation cycles and the day of luteinizing hormone surge was designated day 13 in natural cycles. Endometrial morphology and pinopode numbers were similar in both groups. Fully developed pinopodes appeared in only one sample per cycle, indicating their short life span. However, the cycle day these structures appeared varied up to 5 days between women and the distribution was as follows: day 18 (n = 2), day 19 (n = 7), day 20 (n = 4), day 21 (n = 3), day 22 (n = 1) in ovarian stimulation cycles, and day 20 (n = 2), day 21 (n = 2), day 22 (n = 3) in natural cycles. Furthermore, accelerated pinopode formation in ovarian stimulation cycles was positively correlated with day 13 progesterone. Our findings show that ovarian stimulation does not affect endometrial pinopode formation in terms of quantity and life span. The cycle days when pinopodes form are specific to the individual, being on average 1-2 days earlier in ovarian stimulation than in natural cycles. These changes in pinopode expression may reflect shifts in the window of receptivity, resulting in ovo-endometrial asynchrony and limiting implantation success in in-vitro fertilization.  (+info)

Regulation of matrix metalloproteinase-9 in endometrium during the menstrual cycle and following administration of intrauterine levonorgestrel. (31/1799)

Remodelling of endometrial tissues is fundamental to the cyclical changes that occur during the menstrual cycle, implantation and, in the absence of pregnancy, at menstruation. The enzyme matrix metalloproteinase-9 (MMP-9) is recognized as important in these processes but its regulation is not well defined. These studies have demonstrated that MMP-9 activity is present in the endometrium and exhibits cyclical changes in its distribution in the glandular and stromal cells. MMP-9 protein is present throughout the cycle with highest expression, as determined by semiquantitative analysis of specific MMP-9 immunoreactivity, in glandular cells during the mid secretory phase. A similar distribution was observed in first trimester decidua. In women with a levonorgestrel intrauterine system (LNG-IUS), which delivers high local concentrations of progestagen to the uterine cavity, MMP-9 is highly expressed in both endometrial glandular and stromal cells, and in the vasculature (in endothelial and perivascular cells). It can be concluded that MMP-9 is stimulated directly or indirectly by progesterone. Furthermore, MMP-9 may play a role in the remodelling of the endometrium that occurs during the menstrual cycle and in the aetiology of the morphological changes and breakthrough bleeding associated with long-term progestagen administration via a LNG-IUS.  (+info)

Heat shock proteins in human endometrium throughout the menstrual cycle. (32/1799)

Human endometrium, in response to steroid hormones, undergoes characteristic cycles of proliferation, secretory changes, and tissue shedding. Human endometrium expresses a molecular repertoire which includes the heat shock proteins (Hsps) Hsp27, Hsp60, Hsp70, Hsp90, and alpha crystallin B chain. The expression of Hsp27, Hsp60, and the constitutive form of Hsp70 (Hsc70) shows a sharp increase in human endometrium after ovulation. The maximal expression of the molecular chaperone, alpha crystallin B chain, occurs during the secretory phase. In view of known functions of the Hsps, it is likely that these proteins are involved in protection of the endometrial proteins against factors with the potential to lead to protein denaturation. Tumor necrosis factor-alpha (TNF-alpha) is a cytotoxic cytokine that is produced in progressive amounts during the secretory phase. The function of the Hsps may be to protect cells against the cytotoxic damage of TNF-alpha, particularly during the critical period of "implantation window."  (+info)