Biomedical subjects
Publications and source records attributed to Steven T Nakajima.
A combination of E and progestogens significantly increased matrix metalloproteinase (MMP)-2 in both T47D cells (E(2)-medroxyprogesteroneacetate [MPA] and E(2)-P) and MCF-7 cells (E(2)-MPA, E(2)-P, and equilin-MPA). All combinations resulted in higher MMP-9 levels in MCF-7 cells, but higher MMP-9 levels resulted only with equilin-norethinderone in T47D cells.
BACKGROUND: New low-dose formulations of combination oral contraceptives (COCs) are safe and effective, but they may be associated with an increased risk of breakthrough bleeding. Extending the duration of active hormonal treatment may reduce the frequency of intracyclic bleeding/spotting while maintaining efficacy and tolerability. METHODS: This 6-month, open-label, randomized, active-controlled study involved healthy women aged 18-45 years who were at risk for pregnancy. Women were randomized 4:1 to a 24-day regimen of norethindrone acetate 1 mg/ethinyl estradiol 20 micro g (NETA/EE-24) or to a 21-day regimen of the same combination (NETA/EE-21). The outcomes assessed included pregnancy and incidence, duration of bleeding and intensity of bleeding. RESULTS: The cumulative risk of pregnancy in the NETA/EE-24 group (n=705) was 0.9% during six cycles of treatment. Compared with NETA/EE-21 (n=181), NETA/EE-24 was associated with significantly fewer intracyclic bleeding days (0.95 vs. 1.63; p=.005), fewer days of withdrawal bleeding (2.66 vs. 3.88; p<.001) and fewer total bleeding/spotting days for Cycles 2-6 (18.6 vs. 23.2; p<.001). NETA/EE-24 was well tolerated, and side effects were generally mild to moderate in severity. CONCLUSIONS: NETA/EE-24 is an effective well-tolerated COC that is associated with a bleeding profile more favorable than that of NETA/EE-21.
Matrix metalloproteinases (MMPs) may have a role in the pathogenesis of endometrioma. The level of MMP was lower compared to the level taken after resection of endometrioma.
It is known that women who smoke cigarettes and use oral contraceptives are more likely to have breakthrough bleeding than women who do not smoke. In this article, we review possible mechanisms by which cigarette smoke and its constituents may contribute to irregular bleeding, highlight differences in the activities of nicotine and cigarette smoke, and postulate further studies in the area.
We studied the activity levels of matrix metalloproteinase 1, 2, and 9 in periovulatory fluids from naturally occurring menstrual cycles versus those from samples taken from menstrual cycles stimulated with clomiphene citrate or recombinant stimulating hormone. No statistically significant differences were found.
BACKGROUND: Randomized trials in postmenopausal women have shown a benefit to substituting aromatase inhibitors for tamoxifen or using them sequentially following a full course of tamoxifen. The aromatase inhibitor letrozole has also been utilized for ovarian induction in premenopausal women. CASE REPORT: A premenopausal woman with early stage breast cancer became amenorrheic with adjuvant chemotherapy, and remained so during 5 years of daily tamoxifen. After discontinuing tamoxifen, laboratory studies confirmed an apparent postmenopausal state. Menses resumed following a 2-week course of letrozole. CONCLUSION: Aromatase inhibitors need to be used with caution in women who stop menstruating following adjuvant chemotherapy or tamoxifen.
OBJECTIVE: To characterize the profiles of human chorionic gonadotropin (hCG) secretion in blood and its subsequent excretion in urine during conceptive cycles that ended in successful pregnancy and in spontaneous abortion. DESIGN: A prospective study. SETTING: University fertility clinic and research laboratories. PATIENT(S): Healthy, spontaneously ovulating women with regular menses, no history of infertility, and either no male partner or an azoospermic partner. INTERVENTION(S): Blood and urine samples were collected daily from 63 spontaneously ovulating women during 167 cycles of artificial insemination (AI) with donor semen; hCG concentrations were measured in blood and urine, and luteinizing hormone (LH) and follicle-stimulating hormone (FSH) concentrations were measured in blood by immunoassay. MAIN OUTCOME MEASURE(S): Fecundity, the day of ovulation, the day of hCG detection, and the concentration of hCG on the day of detection in blood and urine. RESULT(S): In 62 conceptions detected, 14 resulted in clinical spontaneous abortion (CAB) and 8 resulted in early pregnancy loss (EPL). When successful pregnancies and pregnancy losses were compared, no significant differences existed between the days of hCG appearance in serum or in urine, the concentrations of hCG on the day of detection, or the incremental change in hCG concentration on the day of detection. CONCLUSION(S): These data validate the use of urinary hCG as a biomarker for assessing peri-implantation pregnancy events.
The plasma profiles of active metalloproteinase (MMP)-1, MMP-2, and MMP-9 levels during the normal menstrual cycle in ovulating, healthy and tubal ligated patients were studied. The active MMP-1 and MMP-9 plasma levels were found to vary in the menstrual cycle. Active MMP-2 levels, however, are constant during the menstrual cycle.
This study demonstrates significant differences in the midluteal concentrations of active matrix metalloproteinase (MMP)-1, MMP-2, and total MMP-3 between patients who conceived and those who did not after day 3 ET.
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OBJECTIVE: To evaluate urinary follicle-stimulating hormone (FSH) as a biomarker for the day of ovulation. DESIGN: Prospective observational study. SETTING: Clinical research center. PATIENT(S): Thirteen women were monitored with measurements of serum and urinary hormones and ovarian ultrasonography during 20 menstrual cycles. Data on urinary hormones and ultrasound evaluations from a total of 65 menstrual cycles from 42 women were analyzed. INTERVENTION(S): Blood and/or urine samples were collected daily. Daily transvaginal ultrasonography was used to detect follicular collapse. MAIN OUTCOME MEASURE(S): LH, FSH, and E(2) were measured in serum. FSH, estrone conjugates (E1C), and pregnanediol-3-glucuronide (PdG) were analyzed in urine. The day of luteal transition (DLT) was calculated using two algorithms. RESULT(S): In 20 cycles, the urinary FSH peak was closer to the day of follicular collapse (-0.85 days) than was the peak day of serum E(2) and the day of luteal transition, as calculated by one algorithm. The FSH peak was not closer to the day of follicular collapse than the peak values of urinary LH, serum FSH, or the day of luteal transition as calculated by a second algorithm. The most consistent correspondence between a hormone peak and ovulation was for serum E(2), serum FSH, serum LH, and urinary FSH. In 65 cycles for which urinary hormone data and ultrasound evaluations were available, the urinary FSH peak occurred within 1 day of follicular collapse in 97% of cycles. CONCLUSION(S): Urinary FSH is a useful biomarker for estimating the day of ovulation in population-based studies.
OBJECTIVE: A multitude of female congenital anomalies are uncommon. However, their impact on reproduction can be profound. The aim of this review is to remind the practicing physician of the clinically relevant embryology and summarize the studies that look at the impact of such various anomalies on a woman's fecundity. We review particular surgical therapies that possibly may improve fertility in such women. DESIGN: Review and critique of available studies in which particular surgical therapies were done and whether they truly improved fertility in these women with congenital reproductive anomalies. RESULTS: Clear evidence demonstrates that uterine septum resection is effective in women with demonstrated recurrent pregnancy losses. Arcuate uterus has little impact on reproduction. Other studies fail to definitively show that surgical correction will improve pregnancy retention or fertility except for specifically indicated clinical scenarios. CONCLUSIONS: The practicing reproductive specialist should have working knowledge of evidence-based therapeutic options for women with reproductive congenital anomalies. A summary chart has been devised to clearly associate embryologic structures with normal adult derivative as well as anomalous structures.
PROBLEM: To assess the modulation of T-cell CD3-zeta chain expression by a factor in the sera of women, prior to egg retrieval and 14 days after an in vitro fertilization (IVF) and to delineate the mechanism of this modulation. METHOD OF STUDY: In this prospective study, blood samples were obtained from 17 patients during an IVF cycle, prior to human chorionic gonadotropin (hCG), and 14 days after embryo return. Serum was incubated with cultured T-lymphocytes (Jurkat cells) for 96 hr and expression of CD3-zeta chain was evaluated. RESULTS: Eight patients had a positive serum hCG titer 14 days after retrieval, while nine patients had a negative hCG titer. Serum from pregnant patients significantly suppressed CD3-zeta chain expression as compared with their sample prior to retrieval (85.6 +/- 6.2%), while subjects not becoming pregnant failed to suppress zeta expression (99.1 +/- 0.9%, P < 0.0001). CONCLUSION: A factor capable of suppressing TcR/CD3-zeta expression can be detected in the sera of pregnant women 14 days after embryo retrieval. Loss of zeta chain was associated with the induction of apoptosis.
Soy contains the isoflavone phytoestrogens, genistein and daidzein. These isoflavones are partial estrogen agonists in cell and animal models, but effects from dietary soy in humans are unclear. Experiments were conducted in pre- and postmenopausal women to examine whether dietary isoflavones from soy behave as estrogen agonists, antagonists or have no effect on the estrogen-sensitive pituitary. Pituitary sensitivity to gonadotropin-releasing hormone (GnRH), an estrogen-sensitive endpoint, was measured during GnRH challenge tests administered before, during and after dietary soy consumption. The response to an isoflavone-rich soy food diet was examined in five premenopausal and seven postmenopausal women using transdermal estrogen replacement therapy. Estrogen agonists suppress gonadotropin concentrations and enhance GnRH priming (enhanced gonadotropin secretion in response to repeated doses of GnRH), whereas antagonists elevate gonadotropin concentrations and have no effect on GnRH priming. Each subject consumed 50 g textured soy protein containing 60 mg total isoflavones daily for 10-14 d. Baseline estradiol concentrations were consistent among study periods. In both pre- and postmenopausal women, soy consumption did not affect mean baseline or peak luteinizing hormone (LH) concentrations, indicating a lack of estrogen-like effect at the level of the pituitary. However, in postmenopausal subjects, mean LH secretion decreased after discontinuing soy, suggesting a residual estrogenic effect. In one premenopausal woman, enhanced LH secretion was observed after soy treatment, suggesting there may be subpopulations of women who are highly sensitive to isoflavones.