Women In Luteal Phase Research Articles

Altered Postural Control during the Luteal Phase in Women with Premenstrual Symptoms

The purpose of this study was to investigate postural control in women with and without premenstrual symptoms (PMS) in three hormonally verified phases of the menstrual cycle. Thirty-two women were recruited to participate in the study and 25 of these women were included in the results. Menstrual cycle phases were determined by sex hormone analyses in serum and LH detection in urine. A prospective rating of PMS was used to divide the subjects into two groups: one with PMS (cyclic) and one without (non-cyclic). For measurement of postural control, subjects stood on a force platform (AMTI^®) in two-legged stance (eyes open and closed) and one-legged stance (eyes open and closed). There were no significant differences in the two-legged stance between the phases of the menstrual cycle or between groups. In one-legged stance with eyes open, there was a significant increase in postural displacement in the mid-luteal phase in the cyclic group, but no differences were detected between phases in the non-cyclic group. These findings may be related to the previously reported increased injury rate and psychomotor slowing in the luteal phase in women with PMS.

Relationship between Sex Hormone-Binding Globulin and Pregnancy Outcome in Women Undergoing Controlled Ovarian Hyperstimulation for Assisted Reproduction

The purpose of this study was to determine whether the changes of sex hormone-binding globulin (SHBG) affect the pregnancy outcome in women undergoing controlled ovarian hyperstimulation (COH) for assisted reproduction. Forty-five infertile women who were undergoing pituitary desensitization and COH for in vitro fertilization (IVF) with or without intracytoplasmic sperm injection (ICSI) and 19 women with normal menstrual cycles participated in the study. Fasting blood samples of the follicular and luteal phases, including follicular fluid during oocyte retrieval, were obtained for determination of estradiol (E(2)), progesterone (P(4)), testosterone (T), and SHBG concentrations. The SHBG levels increased progressively during the course of COH, but remained constant throughout normal menstrual cycles. A positive correlation existed between E(2) and SHBG levels in both the follicular and luteal phases. The mean plasma SHBG concentration and E(2)/T ratio were significantly higher, while the level of T and the free androgen index were significantly lower, in the luteal phase of women who conceived than in those who did not conceive following COH. The changes of follicular fluid SHBG level and E(2)/T ratio were similar to those in plasma. We concluded, therefore, that increases in SHBG in the follicular and luteal phases may be a reflection of the functional state of ovarian stimulation, and further that such elevations may influence the pregnancy outcome through the modulation of circulating estrogen and androgen balance during down-regulated COH cycles for IVF/ICSI.

Serum inhibins, estradiol, progesterone and FSH in surgical menopause: a demonstration of ovarian pituitary feedback loop in women.

The objective of this study was to confirm the source and study the acute changes and relationship between inhibins and FSH at surgical menopause. Regularly cycling women (42-47 years; n = 10) undergoing bilateral oophorectomy for non-ovarian pathology were recruited for this study. One blood sample was taken before surgery and after removal of the ovaries, samples were taken every 15 min up to 1 h, hourly up to 6 h, after 12 h and daily during the hospital admission (3 days). There were five women in the follicular phase and five women in the luteal phase of the cycle. For women in both phases, levels of inhibin A, inhibin B, estradiol (E(2)) and progesterone decreased after the removal of the ovaries. Serum FSH levels started to rise after 12 h in both follicular and luteal phase women after the surgical menopause. Correlation analysis showed that inhibin A and E(2) were significantly negatively correlated in both phases with FSH concentration. Inhibin B had a negative correlation in the follicular phase and progesterone had a negative correlation in the luteal phase. This study showed that ovarian inhibin A and B were cleared from the circulation within 12 h of oophorectomy, whereas E(2) and progesterone remain in the circulation for longer. Negative correlation between FSH, inhibin A and inhibin B suggests that inhibins may contribute to the observed early rise in FSH after the surgical menopause.

Impact of oral contraceptive use on glucocorticoid sensitivity of pro-inflammatory cytokine production after psychosocial stress

We previously reported that women using oral contraceptives (OC) show blunted free cortisol responses to psychosocial stress compared to medication-free women. Low cortisol responses to stress have been shown to be associated with increased susceptibilities to chronic inflammatory and autoimmune processes in animal models and certain human diseases. To address the question if the blunted free cortisol response of OC users may be compensated at the level of the target tissue, we measured hypothalamus–pituitary–adrenal (HPA) axis activation and glucocorticoid (GC) sensitivity of pro-inflammatory cytokine production after psychosocial stress in 14 women using OC and 11 women in the luteal phase of the menstrual cycle. All subjects were exposed to the psychosocial stress paradigm ‘Trier Social Stress Test’ (TSST). Free cortisol was measured repeatedly before and after stress. GC sensitivity was assessed by dexamethasone (DEX) inhibition of lipopolysaccharide (LPS) stimulated production of interleukin-6 (IL-6) in whole blood, immediately before, as well as 10 and 60 min after the stress test. As expected, the stress test induced significant increases in free cortisol in luteal phase women, while OC users showed blunted responses (F= 3.31; p< 0.05). GC sensitivity showed different response patterns; In luteal phase women a slight but not significant decrease was observed throughout the experiment. In contrast, women using OC showed a significant increase in GC sensitivity after stress (F= 3.559; p< 0.05). These results show, that an increase in GC sensitivity of pro-inflammatory cytokine production may at least in part compensate the low cortisol levels seen in OC users after stress. This could be one mechanism to protect women using OC medication from chronic inflammatory and autoimmune diseases.

Cocaine-induced cerebral vasoconstriction differs as a function of sex and menstrual cycle phase

Background: Chronic cocaine abusing women experience fewer cerebral perfusion defects and less neuronal injury than men with comparable drug use histories. This study assessed whether a basis for this discrepancy is a sex difference in cocaine’s acute cerebrovascular effects. Methods: The subjects in this study were 13 healthy and neurologically normal women, reporting occasional cocaine (mean 13, range 1–40 lifetime cocaine exposures). All subjects were administered cocaine (0.4 mg/kg) intravenously, during both the follicular (days 3–8) and luteal (days 18–24) menstrual cycle phases. Dynamic susceptibility contrast magnetic resonance imaging assessments of relative global cerebral blood volume (CBV) changes were conducted on both study days, 10 min after cocaine administration. Results: Cocaine did not alter CBV in follicular phase women, but reduced luteal phase CBV by 10%, indicative of vasoconstriction (analysis of variance [ANOVA], F = 5.1, p < .05). Postcocaine CBV was lower in men administered the drug via an identical protocol relative to follicular phase women (ANOVA, F = 5.4, p < .04). Postcocaine CBV was also lower in the male referent group relative to luteal phase women, but this difference did not achieve statistical significance. No measurable sex or menstrual cycle phase differences in cocaine’s cardiovascular effects were noted. Conclusions: These findings suggest both menstrual cycle phase and sex differences in cocaine’s acute cerebrovascular effects, which may contribute to sex differences in the severity of brain dysfunction found in chronic cocaine abusers. These findings imply that gonadal steroids or the factors they modulate merit study as possible therapeutic agents for reducing cocaine-induced cerebrovascular disorders.

Effect of gender on the development of hypocapnic apnea/hypopnea during NREM sleep.

We hypothesized that a decreased susceptibility to the development of hypocapnic central apnea during non-rapid eye movement (NREM) sleep in women compared with men could be an explanation for the gender difference in the sleep apnea/hypopnea syndrome. We studied eight men (age 25-35 yr) and eight women in the midluteal phase of the menstrual cycle (age 21-43 yr); we repeated studies in six women during the midfollicular phase. Hypocapnia was induced via nasal mechanical ventilation for 3 min, with respiratory frequency matched to eupneic frequency. Tidal volume (VT) was increased between 110 and 200% of eupneic control. Cessation of mechanical ventilation resulted in hypocapnic central apnea or hypopnea, depending on the magnitude of hypocapnia. Nadir minute ventilation in the recovery period was plotted against the change in end-tidal PCO(2) (PET(CO(2))) per trial; minute ventilation was given a value of 0 during central apnea. The apneic threshold was defined as the x-intercept of the linear regression line. In women, induction of a central apnea required an increase in VT to 155 +/- 29% (mean +/- SD) and a reduction of PET(CO(2)) by -4.72 +/- 0.57 Torr. In men, induction of a central apnea required an increase in VT to 142 +/- 13% and a reduction of PET(CO(2)) by -3.54 +/- 0.31 Torr (P = 0.002). There was no difference in the apneic threshold between the follicular and the luteal phase in women. Premenopausal women are less susceptible to hypocapnic disfacilitation during NREM sleep than men. This effect was not explained by progesterone. Preservation of ventilatory motor output during hypocapnia may explain the gender difference in sleep apnea.

Fluoxetine's effect on food craving during the luteal phase in women with premenstrual dysphoric disorder (PMDD)

Fluoxetine's effect on food craving during the luteal phase in women with premenstrual dysphoric disorder (PMDD)

Neuroendocrine response to an intravenous L-tryptophan challenge in women with premenstrual syndrome

Objective: To evaluate the neuroendocrine responses to an intravenous L-tryptophan challenge across the menstrual cycle in women with premenstrual syndrome (PMS) and controls. Design: Controlled clinical study. Setting: The Clinical Research Center of an academic research environment. Patient(s): Women with PMS and healthy volunteers. Intervention(s): An intravenous L-tryptophan challenge was administered two times a week during 1 month to five subjects with prospectively documented PMS and five age- and body mass-matched controls. Main Outcome Measure(s): Whole-blood serotonin, cortisol, and prolactin levels were assessed at the baseline and at 30, 50, 60, 70, 80, and 90 minutes after the challenge. Result(s): Whole-blood serotonin response to the L-tryptophan challenge was blunted in the luteal phase of the menstrual cycle in subjects with PMS compared with controls. Cortisol levels differed between groups and cycle phases only at the baseline, with higher baseline cortisol levels during the luteal phase in women with PMS, whereas baseline and postchallenge prolactin levels did not differ between groups. Conclusion(s): The present results support previously reported findings of alterations in tryptophan handling in women with PMS. The elevated baseline luteal phase cortisol concentrations in subjects with PMS warrants further investigation.

Effects of the menstrual cycle on urodynamic work-up: should we change our practice?

The aim of this study was to compare urinary symptoms and urodynamic parameters during follicular and luteal phases of the menstrual cycle of women with lower urinary tract symptoms. Fifteen women were eligible and agreed to participate in the study. The subjects underwent urodynamic work-up, including filling urethrocystometry, urethral pressure profile and Valsalva leak-point pressure, cough stress test and subjective assessment of severity of symptoms in the mid-follicular and mid-luteal phases of the menstrual cycle. Mean age was 37 years (range 1843), mean parity 1 (range 0-3). Five women were found to have genuine stress urinary incontinence, 6 detrusor instability, 3 mixed incontinence and 1 urethral instability. Clinical diagnosis did not change and the urodynamic parameters were not statistically different in the two separate evaluations. A trend toward worsening of symptoms in the luteal phase in women with detrusor instability was identified. Our study suggests that the menstrual cycle does not significantly affect the work-up of women with lower urinary tract complaints.

Circulating levels of immunoreactive β-endorphin in polycystic ovary syndrome

The plasma levels of β-endorphin were studied in 64 women with polycystic ovarian disease (PCOD) ,from whom was selected a group of 23 women with normal weight and amenorrhea of <36 days. On day 21 ,β-endorphin levels were: mean 64.92 pg/ml; SD 37.32 pg/ml; 95% CI 48.38-81.47 pg/ml. It was also observed that their levels of opioid peptide were reduced ,compared with women who had normal ovulatory cycles ,both in the follicular phase (mean 70.93 pg/ml; SD 24.59 pg/ml; 95% CI 76.84-99.77 pg/ml) and luteal phase (mean 88.30 pg/ml; SD 31.80 pg/ml; 95% CI 76.84-99.77 pg/ml). The results were statistically significant (p < 0.05) for levels in PCOD patients compared with those of the luteal phase in women with normal ovulatory cycles. The decreased levels of β-endorphin were negatively related to luteinizing hormone (LH) levels ,which might explain the rise of LH levels in women with PCOD who control their weight and at the time of amenorrhea ,although it is not clear if central opioid activity is reflected in the peripheral blood.

Sex Steroid Hormones Modulate Serum Ionized Magnesium and Calcium Levels Throughout the Menstrual Cycle in Women

Objective: To determine the serum concentrations of the sex steroid hormones with respect to the concentrations of the biologically active fractions of magnesium and calcium during the different phases of the menstrual cycle. Design: Controlled clinical study. Setting: An academic research environment. Patient(s): Six parous and four nulliparous healthy cycling female volunteers. Main Outcome Measure(s): Concentrations of the sex steroid hormones estrogen, progesterone, and testosterone as well as the ionized Ca and Mg levels were measured in the serum of normal cycling women during five different stages: the menstrual, early follicular, late follicular, ovulatory (ovulatory/early luteal), and luteal phases. Result(s): In each woman, there was a comparatively high ionized Mg level coincident with the early follicular phase, a statistically significant decrease in ionized Mg around the time of ovulation, a significant decrease in ionized and total Mg when the serum progesterone concentration peaked, and a significant increase in the serum Ca 2+/Mg 2+ ratio at both the ovulatory and luteal phases. In addition, a decrease in ionized Mg was found with increased testosterone levels. Conclusion(s): Healthy women of reproductive age demonstrate recurring cycling of ionized Mg and cyclic alterations in the ionized Ca to Mg ratio in their serum. The changes in serum concentrations of these important physiologically active cations, in the range at which they occur, can affect such entities as the vasculature, synaptic transmission, and excitation-secretion coupling and thus can produce the well-known premenstrual syndromes during the luteal phase in women who are somewhat deficient in Mg or in those who have an unusually increased Ca 2+/Mg 2+ ratio.

Menstrual- and gender-dependent variations in circulating IL-1 agonists, antagonists, and binding proteins.

This study tested the hypotheses that sex-related differences in circulating binding proteins for interleukin- 1beta (IL- 1beta ) exist and that these binding proteins affect immunoassays for IL-1beta and IL-1Ra. 125I-labeled IL-1beta was added to human plasma samples, then chromatographed. The percentages of total radioactivity eluting in a high-molecular-weight peak were 21.0 + 0.8 for men (n = 6), 19.1+/-0.9 for follicular phase women (n = 6), and 18.0+/-0.8 in luteal phase women (n = 6; men vs. women, P = 0.032; follicular vs. luteal, P = 0.035), and correlated with plasma sIL-1RII concentrations (r = 0.647, P = 0.007). Plasma IL-1beta immunoreactivity did not correspond to concurrent cellular secretion rates due, in part, to interference in the IL-1beta assay by sIL-1RII. Correspondence between plasma IL-1Ra levels and cellular secretion rates was observed only after serial dilutions of the samples. These results indicate that plasma IL-1beta binding capacity differs between men and women and that sIL-1RII is a major contributing factor. Furthermore, relating plasma IL-1 isoform immunoreactivity to functional measures (tracer binding) or concurrent release by isolated cells can lead to insights about assay interferences that may exist in plasma.

Cardiovascular, endocrine, and receptor measures as related to sex and menstrual cycle phase.

The present study was undertaken to elucidate possible mechanisms underlying sex differences in cardiovascular measures or reactivity to challenge. Because there is vastly diverging literature on the issue, we tried to control for endocrine and psychological factors, which might contribute to some of the apparent discrepancies. Blood pressure, heart rate, adrenaline, and noradrenaline in women (N = 24) and men (N = 14) were examined during baseline and challenge (Stroop Test and Cold Face Test). Adrenoceptor density on lymphocytes (beta 2) and platelets (alpha 2) were determined to examine possible sex differences in underlying cardiovascular mechanisms. Gender effects were controlled by assessing gender role orientation and task appraisal. Women were tested during either the follicular (N = 12) or the luteal (N = 12) phase of the menstrual cycle (verified by estradiol, progesterone, and luteinizing hormone). Follicular and luteal phase women did not differ in any parameter except progesterone. We observed sex-related differences in absolute levels of physiological parameters, the male group having higher systolic blood pressure levels, higher adrenaline plasma concentrations, and significantly more alpha 2-adrenergic receptors. Both challenges elicited pronounced cardiovascular and endocrine responses. Men and women did not differ in response magnitude, in task appraisal, or gender role orientation. The assumption that female sex hormones reduce reactivity to challenge is not supported by our data. The frequently reported male/female differences in reactivity may be caused by an interaction of gender and task characteristics.

Progesterone, 5 α-pregnane-3,20-dione and 3 α-hydroxy-5 α-pregnane-20-one in specific regions of the human female brain in different endocrine states

Post-mortem concentrations of progesterone, 5 α-pregnane-3,20-dione (5 α-DHP) and 3 α-hydroxy-5 α-pregnane-20-one (allopregnanolone) were measured in 17 brain areas and serum in five fertile and five postmenopausal women. Steroid concentrations were measured with radioimmunoassay after extraction of brain tissue with ethanol and purification with celite chromatography. There were regional differences in brain concentrations of all three steroids. The highest progesterone levels were noted in the amygdala, cerebellum and hypothalamus and the highest levels of 5 α-DHP and allopregnanolone were seen in the substantia nigra and basal hypothalamus. Brain concentrations of all three steroids were significantly higher in the fertile women in luteal phase compared to their postmenopausal controls ( P<0.01). In general, the study showed that there is a variation in brain concentrations depending on ovarian steroid production, indicating that the secretion pattern during the menstrual cycle is reflected in the brain. However, regional differences in brain steroid levels imply local mechanisms for steroid uptake and binding as well. Investigations of gonadal steroid distributions in the human brain might be of importance considering the actions of these steroids in the central nervous system. Such studies could provide information about physiological mechanisms, such as the ovulation, and also form a baseline for comparative studies of normal and pathological conditions involving steroids, for instance, catamenial epilepsy and the premenstrual tension syndrome.

Unexplained infertility: Evaluation of the luteal phase; results of the National Center for Infertility Research at Michigan

To evaluate the luteal phase in women with rigorously defined unexplained infertility. Prospective study. National Center for Infertility Research at Michigan. Evaluation of 1,885 women with infertility identified 12 women who met the rigorously defined criteria for unexplained infertility: [1] infertility of > or = 24 months duration, with no male factor, anatomic-functional disorders of the reproductive tract, or immunologic infertility; [2] normal body mass index (BMI); [3] ovulatory cycles ranging from 26 to 32 days; [4] normal luteal phase determined by endometrial biopsy; and [5] normal baseline hormonal profile. Controls (n = 12) were healthy, parous women with normal ovulatory cycles, normal hormonal screen, and were matched for age and BMI to patients. Pattern of follicular growth rate and luteal phase hormonal profile. Women with unexplained infertility did not differ in menstrual cycle characteristics, follicular growth rate or mean preovulatory follicle diameter, or endometrial biopsy dating. The mean levels of P tended to be lower in the unexplained infertility group throughout the luteal phase, but only the midluteal interval reached statistical significance. Luteal phase mean integrated P or urinary PDG levels of unexplained infertility women did not differ from those of fertile controls. The ratio of integrated E2:P also was significantly greater in women with unexplained infertility than in fertile controls. Women with rigorously defined unexplained infertility have subtle hormonal anomalies during the luteal phase when compared with fertile controls.

The Evolution of Endometrial Cycles and Menstruation

According to a recent hypothesis, menstruation evolved to protect the uterus and oviducts from sperm-borne pathogens by dislodging infected endometrial tissue and delivering immune cells to the uterine cavity. This hypothesis predicts the following: (1) uterine pathogens should be more prevalent before menses than after menses, (2) in the life histories of females, the timing of menstruation should track pathogen burden, and (3) in primates, the copiousness of menstruation should increase with the promiscuity of the breeding system. I tested these predictions and they were not upheld by the evidence. I propose the alternative hypothesis that the uterine endometrium is shed/resorbed whenever implantation fails because cyclical regression and renewal is energetically less costly than maintaining the endometrium in the metabolically active state required for implantation. In the regressed state, oxygen consumption (per mg protein/h) in human endometria declines nearly sevenfold. The cyclicity in endometrial oxygen consumption is one component of the whole body cyclicity in metabolic rate caused by the action of the ovarian steroids on both endometrial and nonendometrial tissue. Metabolic rate is at least 7% lower, on average, during the follicular phase than during the luteal phase in women, which signifies an estimated energy savings of 53 MJ over four cycles, or nearly six days worth of food. Thus the menstrual cycle revs up and revs down, economizing on the energy costs of reproduction. This economy is greatest during the nonbreeding season and other periods of amenorrhea when the endometrium remains in a regressed state and ovarian cycling is absent for a prolonged period of time. Twelve months of amenorrhea save an estimated 130 MJ, or the energy required by one woman for nearly half a month. By helping females to maintain body mass, energy economy will promote female fitness in any environment in which fecundity and survivorship is constrained by the food supply. Endometrial economy may be of ancient evolutionary origin because similar reproductive structures, such as the oviducts of lizards, also regress when a fertilized egg is unlikely to be present. Regression of the endometrium is usually accompanied by reabsorption, but in some species as much as one third of the endometrial and vascular tissue is shed as the menses. Rather than having an adaptive basis in ecology or behavior, variation in the degree of menstrual bleeding in primates shows a striking correlation with phylogeny. The endometrial microvasculature is designed to provide the blood supply to the endometrium and the placenta, and external bleeding appears to be a side effect of endometerial regression that arises when there is too much blood and other tissue for complete reabsorption. The copious bleeding of humans and chimps can be attributed to the large size of the uterus relative to adult female body size and to the design of the microvasculature in catarrhines.

Evidence for an altered luteinizing hormone sensitivity to naloxone in pathological hyperprolactinaemia

The underlying mechanisms involved in the pathogenesis of amenorrhoea in hyperprolactinaemic states still remain unclear. Conflicting information exists on the role of endogenous opiates on gonadotrophin disturbances in this pathological condition. In this study we have undertaken a detailed investigation of LH and PRL secretion before and during administration of naloxone, an opioid receptor blocker, in hyperprolactinaemic women with or without ovarian function in order to assess the role of ovarian steroids upon naloxone induced LH and PRL release. Five anovulatory and six ovulatory subjects with hyperprolactinaemia were studied before and during naloxone infusion. Five normo-prolactinaemic ovulatory subjects were included as controls. All ovulatory subjects were studied during the luteal phase of a menstrual cycle. Blood was sampled every 10-20 minutes over a 16-hour period on two alternate days. On study day 1 (control day), subjects received two sets of saline infusion every 6 hours and one saline bolus at the beginning of the seventh hour; on study day 3 (naloxone day), they received a saline infusion during the first 6 hours, an intravenous bolus of naloxone (20 mg) at the beginning of the seventh hour and then a continuous naloxone infusion (1.6 mg/hour) during the ensuing 6 hours. Pituitary LH responsiveness and reserve were assessed on both study days by the subsequent administration of 5 and 95 micrograms of GnRH 4 hours before the completion of each sampling period. Serum concentrations of LH, PRL, oestradiol and progesterone were determined by radioimmunoassay. LH and PRL pulse detection and characteristics were analysed by the Cluster program. Serum PRL levels in hyperprolactinaemic anovulatory and ovulatory subjects were significantly elevated above the normal range. Oestradiol and progesterone serum levels during the luteal phase in women with hyperprolactinaemia and regular menses were similar to those in control ovulatory subjects. Mean LH concentrations increased during naloxone infusion (P < 0.05) in ovulatory hyperprolactinaemia and controls, whereas PRL increased (P < 0.05) only in the group of control subjects. LH pulse amplitude and pulse interval were increased by naloxone (P < 0.05) in all the ovulatory subjects, with no significant changes in anovulatory hyperprolactinaemic women. PRL pulse characteristics were modified significantly by naloxone only in the control group. On day 1, GnRH administration increased LH in all groups, whereas a consistently lower pituitary LH response was observed after naloxone (day 3). Serum PRL levels significantly increased after GnRH administration on day 1 only in normal women, whilst on day 3 this GnRH-dependent PRL releasing effect was significantly attenuated. The absence of stimulatory effects of naloxone on LH in anovulatory hyperprolactinaemia implies that endogenous opiates do not play a significant role in the mechanisms governing hypothalamic amenorrhoea in this syndrome. The results in subjects with ovulatory hyperprolactinaemia suggest the existence of an active role of ovarian steroids on naloxone induced LH release. These data, along with those previously reported in normal women throughout the menstrual cycle, are consistent with the concept that sex steroid hormones contribute to the underlying mechanisms involved in the opioidergic control of LH and PRL release. Whether PRL by itself or through other non-opioid neuroendocrine pathways alters the hypothalamic-gonadotroph unit still requires further investigation.

CA125 and endometriosis

This review covers the literature on CA125 and endometriosis; data on CA125 and oncology are not discussed. In normal women, plasma concentrations of CA125 are increased slightly at ovulation and significantly during menstruation. Marked increases are observed during pregnancy and following peritoneal irritation by infection or surgery. These data are consistent with the concept that CA125 in normal women is mainly derived from the endometrium and the irritated peritoneum. Plasma concentrations of CA125 are markedly elevated in women with cystic ovarian endometriosis and/or deeply infiltrating endometriosis, but not, or only slightly, in the luteal phase of women with minimal or mild endometriosis. This is consistent with the recent concept which considers minimal endometriosis as a normal condition occurring intermittently in many women, in contrast with deep endometriosis and cystic ovarian endometriosis which are called 'endometriotic disease'. Serum CA125 is not a good marker for endometriosis but it is a helpful additional parameter to diagnose endometriotic disease in patients with chronic pelvic pain. Following treatment of endometriosis, elevated plasma concentrations of CA125 could be used as an argument that treatment has been incomplete, or that the condition has recurred. Assaying CA125 in peritoneal fluid requires high sample dilutions or a modified immunoradiometric assay, and until now, its clinical value has been questionable.

Circulating levels of anxiolytic steroids in the luteal phase in women with premenstrual syndrome and in control subjects

Circulating levels of anxiolytic steroids in the luteal phase in women with premenstrual syndrome and in control subjects

Development and validation of a radioimmunoassay for follistatin in human serum.

Follistatin (FS/FSH-suppressing protein/activin-binding protein) is a single-chain glycoprotein, structurally distinct from inhibin, that has been shown to have inhibin-like activity in suppressing FSH secretion both in vivo and in vitro. The aim of these studies was to develop and validate a radioimmunoassay (RIA) for FS in human serum, and to describe the physiological variations of serum FS in humans. Serum was collected from normal men, and normal women in the follicular and luteal phases of the menstrual cycle. Clinical samples were also collected from male patients with hypogonadism, post-menopausal women and pregnant women in the first, second and third trimesters. A RIA for FS in human serum was developed using antisera raised against purified bovine FS and using bovine FS as tracer and standard. Serial dilutions of serum were non-parallel to purified bovine FS standard in the RIA. The addition of sodium dodecyl sulphate (SDS 0.05%) to the assay buffer resolved the non-parallelism suggesting that the interference of serum in the RIA was an assay matrix effect. To characterize the serum FS immunoactivity further, serum was fractionated by gel filtration on Sephadex G-100. At neutral pH, FS immunoactivity eluted as a major peak in the molecular weight range > 200 kDa. In 0.1 M HCl, a second peak of FS immunoactivity eluted in the molecular weight range 30-60 kDa consistent with the known sizes of FS. This suggested that FS was dissociating from a larger complex. Fractions taken from the low molecular weight region diluted in parallel with bovine FS in contrast with fractions from the high molecular weight region which were non-parallel. It is concluded that the non-parallelism of human serum in the FS RIA is due to the binding of serum FS to an unknown high molecular weight factor. This interference is eliminated by the inclusion of 0.05% SDS in the assay buffer. The RIA in 0.05% SDS has been applied to the description of the normal and pathophysiological variations of FS in human serum. There were no significant differences between FS levels in serum from hypogonadal men, normal women in the follicular phase of the menstrual cycle, post-menopausal women and pregnant women from the first, second and third trimesters. FS levels in serum of women in the luteal phase of the menstrual cycle were significantly lower than all other groups. FS levels in normal men were significantly higher than those in both luteal phase women and women in the first trimester of pregnancy (P < 0.05). These findings argue against a role for circulating follistatin in the control of gonadotrophin secretion and suggest that the gonads and/or conceptus are not the primary source of follistatin immunoactivity in serum. The lower follistatin levels in the luteal phase of the menstrual cycle remain unexplained.