Hormonal Profiles of Menstrual Bleeding Patterns During the Luteal-Follicular Transition.

CONTEXT: Menstrual cycle function is determined by a complex endocrine axis that controls the ovaries and endometrium. While the late luteal phase is characterized by declining progesterone and estrogen, how these hormonal profiles relate to menstrual bleeding patterns is not well understood. OBJECTIVE: Characterize associations between luteal phase hormonal profiles and subsequent menstrual bleeding patterns, specifically spotting before bleeding. DESIGN, SETTING, AND PARTICIPANTS: We examined creatinine-adjusted urinary estrone 3-glucuronide (E13G) and pregnanediol 3-glucuronide (Pd3G) levels in relation to spotting in 116 premenopausal women (ages 20-47) who kept daily menstrual diaries and collected first morning urine samples for ≥ 2 consecutive cycles or 1 luteal-follicular transition (n = 283 transitions). We used linear mixed models to estimate associations between luteal phase hormone levels and spotting before bleeding. MAIN OUTCOME MEASURE(S) AND RESULTS: Transitions with ≥ 1 days of spotting before menstrual bleeding (n = 118) had greater luteal phase Pd3G levels vs nonspotting transitions (n = 165). Differences in Pd3G between spotting and nonspotting transitions were largest at menses onset (34.8%, 95% confidence interval, 18.9%, 52.7%). Pd3G levels for spotting transitions dropped to similar levels as nonspotting transitions an average of 1 day later, which aligned with the first day of bleeding for transitions with contiguous spotting. Spotting transitions were preceded by slower rates of Pd3G decline than nonspotting transitions, whereas E13G declines were similar. CONCLUSIONS: Self-reported bleeding patterns may provide insight into luteal phase Pd3G levels. First bleed appears to be the best choice for defining the end of the luteal phase and achieving hormonal consistency across transitions.

alcohol, smoking, and caffeine in relation to fecundability, with effect modification by NAT2.

PURPOSE: Common polymorphisms in the N-acetyltransferase-2 (NAT2) metabolic enzyme determine slow or rapid acetylator phenotypes. We investigated the effects of alcohol, smoking, and caffeine on fecundability, and determined whether the effects were modified by NAT2. METHODS: Three NAT2 polymorphisms were genotyped in 319 women office workers participating in a prospective pregnancy study (1990-1994). Women were ages 20-41 and at risk for pregnancy. Discrete-time survival analysis was used to determine the effects of alcohol, smoking, and caffeine on fecundability and evaluate effect modification by NAT2. RESULTS: We followed 319 women (161 slow acetylators, 158 rapid) for an average of 8 menstrual cycles, resulting in 124 pregnancies. There was no effect of caffeine on fecundability. Drinking ≥1 alcoholic drink per day and current smoking were significantly associated with reduced fecundability, but only among slow acetylators (adjusted fecundability odds ratio [FOR] for smoking = 0.34; 95% confidence interval, 0.22-0.90; adjusted FOR for ≥1 drink per day = 0.20; 0.05-0.92). There was no effect among rapid acetylators. CONCLUSIONS: NAT2 status significantly modified the effects of alcohol and smoking on fecundability, emphasizing the importance of incorporating genetic and metabolic information in studies of reproductive health. Replication of this study is warranted.

Menstrual cycle variability and the likelihood of achieving pregnancy.

The menstrual cycle is an important indicator of underlying hormonal function. Although menstrual cycle variability (sometimes referred to as 'regularity') is associated with a variety of demographic, behavioral, occupational, and environmental factors, as well as with several chronic diseases, few studies have examined its association with fecundity. We investigated whether a woman's menstrual cycle variability was associated with the likelihood of her achieving pregnancy. In this prospective study, we analyzed 3,536 menstrual cycles from 401 women (aged 19-41) recruited from 1990-1994. The women provided daily diaries recording menstrual bleeding, intercourse, and birth control use. Urine samples were assayed for human chorionic gonadotropin to identify early pregnancies during each menstrual cycle. Each woman's menstrual cycle variability was defined by the standard deviation of her cycle lengths during followup. The median follow-up was eight cycles. The outcome was her per-cycle probability of pregnancy. We found that women with high menstrual cycle variability had a reduced (51% lower) per cycle probability of pregnancy (fecundity ratio: 0.49; 95% confidence interval: 0.31, 0.77) compared with women with minimal variability. This relationship was independent of a woman's age and her mean cycle length. Thus, researchers and clinicians using menstrual cycle characteristics as indicators of endocrine or reproductive health should include measures of cycle variability in addition to the more commonly examined cycle length.

Patient counseling women using oral contraceptives.

Oral contraceptives (OCs) are the most widely used form of reversible birth control in the United States. However, incorrect and/or inconsistent use may result in increased failure rates and unintended pregnancies, which present a significant cost burden to the health care system and HMOs. One of the best mechanisms to improve outcomes is through high-quality clinician-patient communication. Managed care organizations may benefit from encouraging their providers to counsel and educate patients on the proper use of OCs, as this may reduce unnecessary follow-up visits, lower the number of unintended pregnancies, and increase patient satisfaction with their health care.

Combined medical and surgical management of rudimentary uterine horn pregnancy.

BACKGROUND: Pregnancy within a noncommunicating rudimentary horn is a known complication of unicornuate uterus. The risk of rupture approximates 50%, most of which occur in the second trimester. CASE: A rudimentary horn pregnancy was discovered at 8 weeks gestation. Medical termination was then performed with fetal intracardiac potassium chloride and intraplacental methotrexate. Magnetic resonance imaging (MRI) of the pelvis was obtained. Laparoscopic uterine horn resection 6 weeks after medical termination was performed. DISCUSSION: While surgical resection of a rudimentary horn pregnancy is necessary, early diagnosis affords the opportunity to take steps that minimize surgical risks. MRI assists surgical planning by demonstrating the form of attachment of the uterine horn to the unicornuate uterus. Preoperative medical termination may decrease vascularity of the gestation, thereby decreasing operative blood loss.

Ovulation induction in a poor responder with panhypopituitarism: a case report and review of the literature.

BACKGROUND: Most women with panhypopituitarism will undergo successful ovulation induction with gonadotropin therapy. Few proven treatment options exist for those who respond poorly to such therapy. A poor response may indicate diminished ovarian reserve, or reflect a deficiency of other key components for ovarian function. CASE: A 31-year-old female with panhypopituitarism and a poor response to gonadotropin therapy took growth hormone (GH) replacement for 4 months prior to restarting gonadotropins. When the serum level of insulin-like growth factor-I normalized, she began ovulation induction with gonadotropins with transdermal estradiol. After 63 days of gonadotropin therapy, she had a leading follicle of 18 mm, followed by follicles of 16.5 mm and 15.5 mm. The serum estradiol was 796 pg/ml, and human chorionic gonadotropin was administered. The patient conceived with timed intercourse. A prior attempt at ovulation induction with gonadotropins alone failed to produce follicular development. CONCLUSION: Prolonged gonadotropin treatment may be necessary to achieve ovulation and avoid the misdiagnosis of ovarian failure. Co-treatment with GH and estrogen may improve the follicular response in a poor responder with panhypopituitarism.

Glycodelin mediates the increase in vascular endothelial growth factor in response to oxidative stress in the endometrium.

OBJECTIVE: We hypothesized that glycodelin stimulates vascular endothelial growth factor (VEGF) expression in response to oxidative stress. STUDY DESIGN: EM42 (human endometrial epithelial cell line) and primary endometrial epithelial cells were subjected to oxidative stress with minimally oxidized low density lipoprotein (mLDL). Cells were also incubated with no LDL (control) or native LDL (nLDL). Each condition was incubated with and without glycodelin antibody. Glycodelin and VEGF protein and messenger RNA (mRNA) levels were analyzed. Primary cells were cultured with glycodelin peptide to evaluate the effect on VEGF protein and mRNA. RESULTS: Glycodelin and VEGF protein and mRNA were higher for cells grown with mLDL (P < .05), while glycodelin antibody attenuated the increase in VEGF protein (P < .01). Glycodelin peptide increased VEGF mRNA and protein (P < .05). CONCLUSION: Glycodelin may act as an autocrine factor within endometriotic implants to increase VEGF expression during oxidative stress.

Effect of glycodelin on the production of vascular endothelial growth factor in cumulus cells.

Glycodelin modulates vascular endothelial growth factor (VEGF) production in cumulus cells in vitro. Patients with normal gonadotropin responses who were undergoing IVF demonstrated increased VEGF production to glycodelin, whereas poor responders had a decreased response to glycodelin.

Menstrual cycle characteristics: associations with fertility and spontaneous abortion.

BACKGROUND: Epidemiologists often use menstrual cycle patterns as indicators of endocrine function in environmental and occupational studies, yet few studies have considered whether menstrual cycle characteristics are associated with fertility or pregnancy outcome. METHODS: We prospectively studied 470 women to determine whether cycle length or bleed length were associated with fertility or spontaneous abortion. Women completed daily diaries with information on menstrual bleeding, intercourse, birth control use, and covariates. For each menstrual cycle, women collected at least 2 urine samples, which were assayed for human chorionic gonadotropin to define early pregnancies. Women were followed for 1 year or until the end of a clinical pregnancy. RESULTS: Cycles with lengths of 30 to 31 days preceded cycles with the highest fecundity. Shorter cycles were less likely to be followed by conception (fecundity ratio [FR] = 0.6; 95% confidence interval [CI] = 0.4-1.0). Compared with 30- to 31-day cycles, conceptions after shorter and longer cycles were more likely to be spontaneously aborted (for shorter cycles, odds ratio [OR] = 3.0 [95% CI = 0.9-9.6] and for longer cycles, OR = 3.0 [0.9-10.6]). Cycles with 5 days of menstrual bleeding had the highest fecundity. Cycles with up to 4 days of bleeding had lower fecundity (for bleed lengths of 4 days, FR = 0.5 [0.3-0.8] and for bleed lengths less than 4 days, FR = 0.6 [0.3-0.9]). Spontaneous abortion was less likely after bleeds greater than 5 days (OR = 0.4 [0.1-1.1]) when compared with 5-day bleeds. CONCLUSIONS: Menstrual cycle characteristics appear to be associated with fertility and spontaneous abortion.

RU486 inhibits expression of lysophosphatidic acid induced glycodelin.

OBJECTIVE: This study was undertaken to provide evidence for the mode of action of RU486 on glycodelin produced in K562 cells. To show that histiocytes may be a source of glycodelin in leiomyoma. STUDY DESIGN: With the use of K562, a leukemia cell line, the effect of lysophosphatidic acid (LPA), RU486, antioxidants, and ZK112,993 on glycodelin protein and gene expression was studied. Immunocytochemistry for glycodelin and HAM-56 (macrophage) was performed on leiomyoma and myometrium. RESULTS: Incubation of K562 cells with LPA, progesterone, ZK112,933 and RU486 significantly induced the expression of glycodelin protein and messenger RNA. The addition of RU486 to LPA activated cells markedly reduced expression of glycodelin. Addition of ZK112,993, an antiprogestin without antioxidant properties, to LPA activated cells did not reduce glycodelin. Histiocytes in leiomyoma and myometrium co-localize with glycodelin. CONCLUSION: RU486, partly acting as an antioxidant, markedly reduces LPA stimulated glycodelin production. Histiocytes in leiomyoma and myometrium immunostain for glycodelin and suggests a source for glycodelin in leiomyoma.