Normal Human Menstrual Cycle Research Articles

Cyclic regulation of LPA3 in human endometrium

Lysophosphatidic acid (LPA) belongs to the group of lipid messengers, which plays a pivotal role in the establishment of implantation via its cellular receptor, LPA3. The aims of the present study were to characterize LPA3 mRNA and protein in human endometrium during the normal human menstrual cycle. Forty-three normally cycling volunteers without reproductive disorders were randomized to undergo endometrial sampling on a specific cycle day. Samples were assessed for relative LPA3 mRNA expression using real-time PCR and for LPA3 protein using immunohistochemistry and western blot. The expression of LPA3 mRNA significantly increased during the early and late secretory phase compared with other menstrual phases. LPA3 protein was localized to the epithelial and stromal cells and expression levels followed the same pattern as for LPA3 mRNA. In the normal human menstrual cycle, LPA3 mRNA and protein expression also change, indicating that this gene may be related to the function of the endometrium.

No Association between Matrix Metalloproteinase (MMP)-1, MMP-3, and MMP-7 SNPs and Endometrial Cancer Risk

The matrix metalloproteinases (MMP) function as regulators of the dynamic tissue remodeling that occurs in the endometrial lining of the uterus during the normal human menstrual cycle; dysregulation of the MMPs is thought to contribute to the development of both endometriosis and endometrial cancer

Cyclic regulation of transcription factor C/EBP beta in human endometrium

BackgroundThe transcription factor CCAAT/enhancer-binding protein (C/EBP) beta is a critical mediator of murine endometrial function during embryo implantation. Our objective is to characterize changes in C/EBP beta mRNA abundance and protein localization over the normal human menstrual cycle.MethodsFifty normally cycling volunteers without reproductive disorders were randomized to undergo endometrial sampling on a specific cycle day, with secretory phase samples timed using urinary LH surge. Samples were assessed for relative C/EBP beta mRNA expression using quantitative real-time RT-PCR and for C/EBP beta protein localization using immunohistochemistry. The semiquantitative histologic scoring (HSCORE) system was used to compare staining intensity in each tissue compartment between each cycle phase.ResultsC/EBP beta mRNA expression by whole endometrium peaks in the late secretory phase and is significantly higher than that in the proliferative and mid-secretory phases. A marked increase in nuclear C/EBP beta protein immunostaining is seen in stromal cells beginning about cycle day 20, coincident with the start of endometrial receptivity. This increased staining continues for the remainder of the cycle.ConclusionIn the normal human menstrual cycle, C/EBP beta mRNA and protein expression also change, with increased nuclear immunostaining in the mid-secretory phase, suggesting a possible role for C/EBP beta in human endometrial receptivity.

Cyclic regulation of transcription factor C/EBPβ in human endometrium

The transcription factor CCAAT/enhancer-binding protein β (C/EBPβ) is a critical mediator of murine endometrial epithelial and stromal cell proliferation and differentiation. Consequently, female mice lacking the C/EBPβ gene are infertile. Previous studies have demonstrated the presence of C/EBPβ mRNA in human endometrium and upregulation of C/EBPβ during in vitro stromal decidualization. In order to further define the role of C/EBPβ in human endometrium, we characterized temporal changes in C/EBPβ mRNA abundance over the normal human menstrual cycle.

285. Endometrial lymphatics are reduced in the functionalis compared to basalis and myometrium

Information on uterine lymphatics is limited. The aim of this study was to characterise uterine lymphatic vessels and the corresponding growth factors in the endometrium and myometrium across the normal human menstrual cycle. Uterine tissues were collected from patients undergoing hysterectomy. Lymphatic and microvascular density (MVD/mm2) was determined on serial sections of full thickness uterus (n = 45) with antibodies to D2-40, CD31, CD34 and FVIII. Lymphangiogenic growth factors VEGF-C and VEGF-D immunolocalisation was also determined on serial sections. VEGF-C, VEGF-D and lymphatic endothelial cell markers VEGF-R3 and D2-40 protein expression was determined on protein extracted from myometrium and endometrium and separated by SDS-PAGE from proliferative (n = 5) and secretory (n = 5) hysterectomy specimens. The lymphatic vessels were closely associated with smooth muscle cells of spiral arterioles and VEGF-C and VEGF-D were primarily localised in the endometrial glands, luminal epithelium and myometrial smooth muscle bundles. The lymphatic MVD was significantly reduced in the functionalis (15.1 ± 2.3mm2) compared to basalis (80 ± 11.4mm2) and myometrium (63 ± 9.2mm2). Overall, lymphatics constituted 12% of all vessels in the functionalis, 60 % in the basalis and 30% of the myometrium. D2-40 positive uterine lymphatics showed considerable heterogeneity, with 88% co-localisation with the blood vessel marker CD31, but only 46% expressing CD34 and 31% with FVIII. Protein expression of VEGF-C, VEGF-D, VEGF-R3 and D2-40 were significantly reduced during the proliferative phase compared to the secretory phase and were also significantly reduced in the endometrium compared to the myometrium across the cycle (P ≤ 0.05). Endometrial functionalis lymphatics are reduced in conjunction with a reduction in lymphangiogenic growth factors compared with the myometrium.

Cytokine production by peripheral blood monocytes during the normal human ovulatory menstrual cycle.

There is considerable evidence that hormone-driven changes resembling an inflammatory response occur in the vascular compartment during the menstrual cycle, and peripheral blood monocytes may be central in the process. We investigated whether there is a cyclical change in intrinsic production of pro-inflammatory cytokines by monocytes in the ovulatory menstrual cycle, and whether there is a circulating factor that influences the pattern of cytokine production in a cyclical manner. Monocytes were purified by density-gradient centrifugation followed by countercurrent centrifugal elutriation, from the blood of normal women (n = 10) pre- and post-ovulation. Monocytes were cultured under basal conditions with bacterial lipopolysaccharide (LPS), and to determine the effects of circulating factors, incubations were also conducted in the presence of autologous serum. Concentrations of interleukin (IL)-1alpha, IL-1beta, IL-6, tumour necrosis factor (TNF)-alpha and IL-1 receptor antagonist (IL-1Ra) were measured by sandwich ELISA. The majority of IL-1alpha and IL-1beta was cell associated, while the other cytokines were almost entirely secreted. Basal levels of IL-1alpha, IL-1beta, and TNF-alpha were significantly increased following ovulation, while there was no significant change in levels of secretion of IL-6 or IL-1Ra. These effects were present in unstimulated cells, suggesting prior activation in vivo. Cytokine production was increased in response to LPS; however, there was no consistent effect of autologous serum. Intrinsic production of pro-inflammatory cytokines by monocytes is increased following ovulation.

Central pulse pressure and proximal aortic stiffness remain unchanged during the normal human menstrual cycle

Central pulse pressure and proximal aortic stiffness remain unchanged during the normal human menstrual cycle

Modulation of natural killer cells by cortisol and biogenic amines during the course of the normal human menstrual cycle

Modulation of natural killer cells by cortisol and biogenic amines during the course of the normal human menstrual cycle

Gonadotropins and Cytokines Affect Luteal Function through Control of Apoptosis in Human Luteinized Granulosa Cells

The luteal phase in the normal human menstrual cycle is known to be about 14 days. The physiological mechanisms that regulate the corpus luteum remain to be clarified, although apoptosis is reported to be involved. This study was undertaken to investigate the regulation of luteal function by gonadotropins, cytokines, and PGs, concentrating attention on the incidence of apoptosis and its molecular mechanisms in cultured human luteinized granulosa cells collected at oocyte pick-up from patients undergoing in vitro fertilization and embryo transfer. Clusters of granulosa cells were pipetted in 0.1% hyaluronidase in phosphate-buffered saline. After cell separation by centrifugation using Ficoll-Paque, 1 × 104 viable cells/mL in RPMI 1640 medium with 10% FCS were used for experimentation. Substances added were FSH (100 ng/mL), hCG (100 ng/mL), LH (100 ng/mL), interleukin-1β (IL-1β; 10 ng/mL), transforming growth factor-β1 (TGFβ1; 10 ng/mL), macrophage colony-stimulating factor (M-CSF; 10 ng/mL), tumor necrosis factor-α (TNFα; 10 ng/mL), and PGF2α (10 ng/mL). After 24-h culture at 37 C under 5% CO2 and air, cells were fixed with 4% neutral buffered formalin and stained with Hoechst 33258. Apoptotic bodies were counted under a fluorescence microscope, and immunostaining was performed using anti-Fas, Fas ligand, Bcl-2, Bax, and p53 antibodies. Incidences of apoptotic bodies in the group without substance addition were 0.7 ± 0.2% (0 h), 5.9 ± 0.6% (24 h), and 7.9 ± 1.2% (48 h); spontaneous increase was significant at the latter time points. Defining the incidence at 24 h as 100%, values after treatment were: FSH, 57%; LH, 84%; hCG, 44%; IL-1β, 76%; TGFβ1, 52%; M-CSF, 50%; TNFα, 177%; and PGF2α, 147%. Significant suppression was observed with FSH, hCG, TGFβ1, and M-CSF (P < 0.01). On the other hand, significant induction occurred with TNFα and PGF2α (P < 0.01). On immunostaining, the incidence of stained cells with anti-Fas, Fas ligand, Bax, and p53 antibody was increased after 24-h incubation without addition. This was reduced by hCG, TGFβ1, and M-CSF. No stained cells were observed with anti-Bcl-2 antibody before or after incubation. In conclusion, our results suggest that both gonadotropins (FSH and hCG) and cytokines (TGFβ1 and M-CSF) may be involved in the support of luteal function via suppression of apoptosis, and that TNFα and PGF2α may contribute to ovarian dysfunction and/or luteal regression via its induction in human luteinized granulosa cells. Our results also suggest that Fas, Fas ligand, p53, and Bax may play roles in this apoptosis controlled by hCG, TGFβ1, and M-CSF.

Gonadotropins and cytokines affect luteal function through control of apoptosis in human luteinized granulosa cells.

The luteal phase in the normal human menstrual cycle is known to be about 14 days. The physiological mechanisms that regulate the corpus luteum remain to be clarified, although apoptosis is reported to be involved. This study was undertaken to investigate the regulation of luteal function by gonadotropins, cytokines, and PGs, concentrating attention on the incidence of apoptosis and its molecular mechanisms in cultured human luteinized granulosa cells collected at oocyte pick-up from patients undergoing in vitro fertilization and embryo transfer. Clusters of granulosa cells were pipetted in 0.1% hyaluronidase in phosphate-buffered saline. After cell separation by centrifugation using Ficoll-Paque, 1 x 104 viable cells/mL in RPMI 1640 medium with 10% FCS were used for experimentation. Substances added were FSH (100 ng/mL), hCG (100 ng/mL), LH (100 ng/mL), interleukin-1beta (IL-1beta; 10 ng/mL), transforming growth factor-beta1 (TGFbeta1; 10 ng/mL), macrophage colony-stimulating factor (MCSF; 10 ng/mL), tumor necrosis factor-alpha (TNFalpha; 10 ng/mL), and PGF2alpha (10 ng/mL). After 24-h culture at 37 C under 5% CO2 and air, cells were fixed with 4% neutral buffered formalin and stained with Hoechst 33258. Apoptotic bodies were counted under a fluorescence microscope, and immunostaining was performed using anti-Fas, Fas ligand, Bcl-2, Bax, and p53 antibodies. Incidences of apoptotic bodies in the group without substance addition were 0.7 +/- 0.2% (0 h), 5.9 +/-0.6% (24 h), and 7.9 +/- 1.2% (48 h); spontaneous increase was significant at the latter time points. Defining the incidence at 24 h as 100%, values after treatment were: FSH, 57%; LH, 84%; hCG, 44%; IL-1beta, 76%; TGFbeta1, 52%; M-CSF, 50%; TNFalpha, 177%; and PGF2alpha, 147%. Significant suppression was observed with FSH, hCG, TGFbeta1, and M-CSF (P < 0.01). On the other hand, significant induction occurred with TNFalpha and PGF2alpha (P < 0.01). On immunostaining, the incidence of stained cells with anti-Fas, Fas ligand, Bax, and p53 antibody was increased after 24-h incubation without addition. This was reduced by hCG, TGFbeta1, and M-CSF. No stained cells were observed with anti-Bcl-2 antibody before or after incubation. In conclusion, our results suggest that both gonadotropins (FSH and hCG) and cytokines (TGFbeta1 and M-CSF) may be involved in the support of luteal function via suppression of apoptosis, and that TNFalpha and PGF2alpha may contribute to ovarian dysfunction and/or luteal regression via its induction in human luteinized granulosa cells. Our results also suggest that Fas, Fas ligand, p53, and Bax may play roles in this apoptosis controlled by hCG, TGFbeta1, and M-CSF.

Endometrial perfusion across the normal human menstrual cycle assessed by laser Doppler fluxmetry.

This study investigated variations in microvascular perfusion of human endometrium across the menstrual cycle, using a laser Doppler technique to assess red blood cell (RBC) flux. Endometrial RBC flux was monitored by laser Doppler fluxmetry via a fibre optic probe inserted transvaginally into the uteri of 19 conscious normal volunteer women, on four occasions at weekly intervals over one menstrual cycle. Regional variation in RBC flux was investigated in 16 surgical patients under general anaesthesia and in five excised uteri. Endometrial perfusion exhibited short-term temporal variations consistent with the cardiac cycle and often also showed vasomotion (5-12 cycles/min). Mean endometrial perfusion differed between phases of the menstrual cycle in conscious women, being highest during early proliferative and early follicular phases. There were no significant regional differences in local mean endometrial perfusion in anaesthetized patients. No evidence of endometrial ischaemia/reperfusion episodes was found in any subject using this technique. This study provides benchmark data of variations in RBC flux per unit volume of tissue in the luminal approximately 1 mm of endometrium, across the normal human menstrual cycle. Flux values were highest at times associated with endometrial growth and preparation for implantation, indicating that RBC flux may be a useful parameter for assessment of endometrial physiology.

Changes in peripheral serum levels of total activin A during the human menstrual cycle and pregnancy.

The main objective of this study was to determine whether activin A concentrations in peripheral blood fluctuate during the normal human menstrual cycle and pregnancy. Blood samples were collected longitudinally from five regularly cycling volunteers (22-30 yr) throughout a spontaneous menstrual cycle and cross-sectionally from normal pregnant women attending the antenatal clinic (8-38 weeks gestation: 3-20 subjects/time point). Total (i.e. bound plus free) activin A concentrations were measured using a recently developed two-site enzyme immunoassay that employs an analyte denaturation/oxidation step to eliminate interference due to endogenous activin-binding proteins. During the menstrual cycle, mean serum activin A levels varied in a biphasic manner (by ANOVA, P = 0.02), with highest levels around midcycle (approximately 220 pg/mL) and the late luteal/early follicular phase (approximately 310 pg/mL) and nadirs in both midfollicular (approximately 125 pg/mL) and midluteal (approximately 120 pg/mL) phases. Between the mid- to late luteal phase, the activin A level increased progressively (approximately 2.5-fold; P < 0.05), whereas inhibin A, estradiol, and progesterone all decreased progressively (approximately 10-fold; P < 0.001). During pregnancy, serum activin A levels were much higher than those in nonpregnant subjects, with a value of 2.12 +/- 0.31 ng/mL recorded in week 8. Levels remained at approximately 2 ng/mL between weeks 8-24, but increased thereafter to reach 25.5 +/- 6 ng/mL by week 38, a value approximately 100 times greater than that during the normal menstrual cycle. Serum activin A levels during pregnancy were significantly correlated with inhibin A (r = 0.69; P < 0.001), estradiol (r = 0.55; P < 0.001), and progesterone (r = 0.74; P < 0.001) values. Gel permeation chromatography indicated that all of the detectable activin A in human follicular fluid, pregnancy serum, and term placental extract eluted with an apparent molecular mass between 70-200 kDa, indicating that little, if any, free activin (molecular mass, 25 kDa) is present in these samples. Although these results support a possible endocrine role for circulating activin A during the human menstrual cycle and pregnancy, the observation that all detectable activin A is associated with binding protein(s) raises questions about its relative bioavailability for action on peripheral target cells.

Mood, pain and the menstrual cycle: potential confounding factors in automated perimetry?

The main purpose of this study was to investigate the effect of the normal human menstrual cycle on the central visual field as measured with program 24‐2 of the Humphrey Field Analyser. Subject groups comprised 18 normally menstruating women (F), and control groups of eight women taking oral contraceptives (P), and four men (M). Subjects attended 2–3 times weekly for 6‐10 weeks and were unaware of the purpose of the study. Daily self‐report questionnaires were used to aid the study's disguise and to assess mood and physical symptomatology. Overall, there was a large degree of inter‐ and intrasubject variability. Analysis of variance failed to identify repeatable fluctuations in visual field performance across menstrual cycle phase in P or F, or across a randomly allocated 28‐day cycle in M. However, curve‐fitting techniques identified a significant cosine curve in mean sensitivity of the visual field in group F over three cycles as a whole (P = 0.03), suggesting peaks of sensitivity around mid‐cycle with low points paramenstrually. The extent of this fluctuation was 0–0.5 dB and therefore within normal limits and not clinically significant. Physical symptoms of abdominal pain and backache were greater paramenstrually in all women, with no repeatable cyclical pattern in symptoms of mood in either group of women. Overall, men reported higher scores of both mood swings and positive mood, and similar scores of irritability as women. Mean sensitivity and short‐term fluctuation of the visual field were not found to be dependent upon mood and physical symptomatology, or with day of the week. In conclusion, it is unlikely that fluctuations in performance associated with the menstrual cycle, mood and physical symptoms are sufficient to confound interpretation of the results of automated perimetry.

Mood, pain and the menstrual cycle: potential confounding factors in automated perimetry?

The main purpose of this study was to investigate the effect of the normal human menstrual cycle on the central visual field as measured with program 24-2 of the Humphrey Field Analyser. Subject groups comprised 18 normally menstruating women (F), and control groups of eight women taking oral contraceptives (P), and four men (M). Subjects attended 2–3 times weekly for 6-10 weeks and were unaware of the purpose of the study. Daily self-report questionnaires were used to aid the study's disguise and to assess mood and physical symptomatology. Overall, there was a large degree of inter- and intrasubject variability. Analysis of variance failed to identify repeatable fluctuations in visual field performance across menstrual cycle phase in P or F, or across a randomly allocated 28-day cycle in M. However, curve-fitting techniques identified a significant cosine curve in mean sensitivity of the visual field in group F over three cycles as a whole (P = 0.03), suggesting peaks of sensitivity around mid-cycle with low points paramenstrually. The extent of this fluctuation was 0–0.5 dB and therefore within normal limits and not clinically significant. Physical symptoms of abdominal pain and backache were greater paramenstrually in all women, with no repeatable cyclical pattern in symptoms of mood in either group of women. Overall, men reported higher scores of both mood swings and positive mood, and similar scores of irritability as women. Mean sensitivity and short-term fluctuation of the visual field were not found to be dependent upon mood and physical symptomatology, or with day of the week. In conclusion, it is unlikely that fluctuations in performance associated with the menstrual cycle, mood and physical symptoms are sufficient to confound interpretation of the results of automated perimetry.

Changes in ocular and visual variables during the menstrual cycle.

For most women the menstrual cycle is an integral part of a major portion of their lives. There is widespread agreement about the hormonal changes that occur during the menstrual cycle, but studies of physical and psychological changes have been more controversial. The influence of the menstrual cycle on various ocular and visual variables has been investigated. These include the potential protective role of female sex hormones in some ocular conditions, reports of reduced tolerance to contact lens wear, and changes in visual performance during the cycle. This paper critically reviews the literature on visual and ocular changes across the normal human menstrual cycle. Stereotypical views of an impairment of performance premenstrually and during menstruation are challenged. The shortcomings of, and difficulties associated with, much of the research on this topic are highlighted.

More basic forms of both human follicle-stimulating hormone and luteinizing hormone in serum at midcycle compared with the follicular or luteal phase.

The purpose of this study was to compare the heterogeneity and median charge of FSH and LH in serum at different phases of the normal human menstrual cycle. Serum specimens were obtained during the follicular phase [9.0 +/- 1.9 (+/- SD) days before the midcycle], at the midcycle LH peak, and during the luteal phase (9.75 +/- 1.6 days after the midcycle) in 16 women with normal menstrual cycles. The 48 serum specimens were subjected to electrophoresis in 0.17% agarose suspension in 0.075 M veronal buffer at pH 8.6, using a column suitable for measuring the median charge of the isoforms of FSH and LH, expressed as median electrophoretic mobility. Four sera were also analyzed by use of a larger column, giving a high resolution. The FSH and LH activities were measured with a time-resolved sandwich fluoroimmunoassay. The number of isoforms of both FSH and LH in each serum specimen analyzed by electrophoresis with high resolution was between 20-30. The median charge of the isoforms of FSH was less negative (P < 0.001) at the midcycle than in the follicular or luteal phase in all 16 women. The same was found for LH in 14 of 15 women. The median charge of FSH or LH in the follicular phase was not significantly different from that in the luteal phase of the cycle. We conclude that at least 20-30 isoforms of both FSH and LH circulate in blood during the menstrual cycle. More basic isoforms of both hormones appear in serum at midcycle than in the follicular or luteal phase. The difference is most likely due to a selective secretion from the pituitary of more basic forms of FSH and LH at midcycle.

Computer-assisted observations of the normal menstrual cycle: predicting the day of ovulation

To develop a probabilistic computer model to predict the preovulatory days of the menstrual cycle by given hormonal parameters such as follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), and progesterone (P). A computerized analysis program is specifically designed for the normal human menstrual cycle. The algorithm of this model incorporates the statistical aspects and the daily variations of FSH, LH, E2, and P. This study includes 16 healthy fertile women with ovulatory cycles. Daily venous blood samples were collected from each subject from the first to the last day of the menstrual cycle. Radioimmunoassays were used to measure the four hormones in each blood sample. The computer implementation of this menu driven code that is flexible to accommodate differences in the hormone measurement procedures was accomplished. The distribution of measured hormone concentrations was validated to be normal. The best estimation of the ovulation day was highly dependent on the use of the band width (acceptable range) of the daily SD, which was +/- 1.45 in our laboratory. This computer model, heretofore named the CESME (Computer Enhanced Systems in Medicine and Engineering) developed by two of the authors, Ger and Karamete, with its reconfigurability enables the user to adopt the program to the normal values in their laboratory and use its clinically for predicting the probable periovulatory day(s) of the menstrual cycle.

Immunocytochemical localization of inhibin α-subunit in the human corpus luteum

The localization of inhibin alpha-subunit within the human corpus luteum was investigated. The antiserum used was raised in sheep against the first 1-23 amino acid sequence of the N-terminus of the human inhibin alpha-subunit. Using the avidin-biotin immunoperoxidase technique, intense immunostaining was localized within the granulosa-lutein cells of the corpus luteum, with absence of staining in the theca-lutein cells and surrounding ovarian tissue. Similar distribution of inhibin alpha-subunit immunostaining was observed in 12 corpora lutea obtained during the early, mid- and late-luteal phases and no changes in intensity were apparent at these different stages. Negative controls were obtained by applying antiserum which had been preabsorbed overnight with excess inhibin peptide in place of primary antiserum and also normal nonimmune sheep serum as a substitute for primary antiserum. These results provide further evidence that the human corpus luteum is a significant source of immunoreactive inhibin during the normal human menstrual cycle. The specific localization within the granulosalutein cells of the corpus luteum suggests that inhibin alpha-subunit production may originate from a discrete cell population within the human corpus luteum.

Changes in Nuclear and Nucleolar Areas of Endometrial Glandular Cells Throughout the Menstrual Cycle

Reproducible measures of the ultrastructural changes occurring throughout the normal human menstrual cycle are useful for defining and differentiating between normal and pathological states. Glandular endometrial functionalis epithelium obtained from five menstrual cycle subphases (early and late proliferative; and early, middle and late secretory) has been quantitated and compared for changes in nuclear and nucleolar size. These analyses indicate that (a) nuclear area significantly increases in the late secretory subphase, perhaps a requirement of endometrial regeneration; (b) nucleolar area peaks during the early secretory subphase, a necessary prelude for the later increased secretory activity; and (c) nucleolar area declines in the middle and late secretory subphases, probably due to falling hormone blood levels late in the cycle. In the proliferative phase, the majority of cells containing large nuclei and nucleoli have a relatively undeveloped cytoplasm, while the cytoplasm of those in the secretory phase contains glycogen. These cells were termed Stage 1 and 2 cells, respectively. The late secretory subphase contains some degenerating mature epithelial cells with large nuclei and small nucleoli as well as differentiated and regenerating cells with larger nucleoli. These measures establish a baseline of the normal changes in nuclear and nucleolar size as they occur throughout the normal human menstrual cycle.

Recombinant DNA—Derived Human Luteinizing Hormone: Basic Science Rapidly Applied to Clinical Medicine

The normal human menstrual cycle is characterized by an early rise in the level of follicle-stimulating hormone (FSH), which acts on a group of responsive ovarian follicles. Without the FSH, these follicles would have failed to grow and mature. Thus, FSH rescues a group of follicles. Although the majority will proceed to atresia, one or more will mature to the preovulatory stage. Estradiol secreted by the preovulatory follicles will, at an appropriate time, induce a surge in luteinizing hormone (LH) secretion, which triggers oocyte maturation and ovulation. Follicular stimulation and induction of ovulation using exogenous gonadotropins is, in effect, an attempt to mimic these events. For almost 30 years, human menopausal gonadotropin, an admixture of 75 mIU/mL of purified FSH and LH extracted from the urine of postmenopausal women, has been administered during the follicular phase to stimulate folliculogenesis. See also p 3290. Follicular development is monitored by ultrasonography and