Compensatory Increase in Ovarian Aromatase in Older Regularly Cycling Women.

CONTEXT: Serum estradiol (E2) levels are preserved in older reproductive-aged women with regular menstrual cycles despite declining ovarian function. OBJECTIVE: The objective of the study was to determine whether increased granulosa cell aromatase expression and activity account for preservation of E2 levels in older, regularly cycling women. DESIGN: The protocol included daily blood sampling and dominant follicle aspirations at an academic medical center during a natural menstrual cycle. SUBJECTS: Healthy, regularly cycling older (36-45 y; n = 13) and younger (22-34 y; n = 14) women participated in the study. MAIN OUTCOME MEASURES: Hormone levels were measured in peripheral blood and follicular fluid aspirates and granulosa cell CYP19A1 (aromatase) and FSH-R mRNA expression were determined. RESULTS: Older women had higher FSH levels than younger women during the early follicular phase with similar E2 but lower inhibin B and antimullerian hormone levels. Late follicular phase serum E2 did not differ between the two groups. Follicular fluid E2 [older (O) = 960.0 [interquartile range (IQR) 765.0-1419.0]; younger (Y) = 994.5 [647.3-1426.5] ng/mL, P = 1.0], estrone (O = 39.6 [29.5-54.1]; Y = 28.8 [22.5-42.1] ng/mL, P = 0.3), and the E2 to testosterone (T) ratio (O = 109.0 ± 41.9; Y = 83.0 ± 18.6, P = .50) were preserved in older women. Granulosa cell CYP19A1 expression was increased 3-fold in older compared with younger women (P < .001), with no difference in FSH-R expression. CONCLUSIONS: Ovarian aromatase expression increases with age in regularly cycling women. Thus, up-regulation of aromatase activity appears to compensate for the known age-related decrease in granulosa cell number in the dominant follicle to maintain ovarian estrogen production in older premenopausal women.

Accumulated deep sleep is a powerful predictor of LH pulse onset in pubertal children.

CONTEXT: During puberty, reactivation of the reproductive axis occurs during sleep, with LH pulses specifically tied to deep sleep. This association suggests that deep sleep may stimulate LH secretion, but there have been no interventional studies to determine the characteristics of deep sleep required for LH pulse initiation. OBJECTIVE: The objective of this study was to determine the effect of deep sleep fragmentation on LH secretion in pubertal children. DESIGN AND SETTING: Studies were performed in a clinical research center. SUBJECTS: Fourteen healthy pubertal children (11.3-14.1 y) participated in the study. INTERVENTIONS: Subjects were randomized to two overnight studies with polysomnography and frequent blood sampling, with or without deep sleep disruption via auditory stimuli. RESULTS: An average of 68.1 ±10.7 (± SE) auditory stimuli were delivered to interrupt deep sleep during the disruption night, limiting deep sleep to only brief episodes (average length disrupted 1.3 ± 0.2 min vs normal 7.1 ± 0.8 min, P < .001), and increasing the number of transitions between non-rapid eye movement (NREM), REM, and wake (disrupted 274.5 ± 33.4 vs normal 131.2 ± 8.1, P = .001). There were no differences in mean LH (normal: 3.2 ± 0.4 vs disrupted: 3.2 ± 0.5 IU/L), LH pulse frequency (0.6 ± 0.06 vs 0.6 ± 0.07 pulses/h), or LH pulse amplitude (2.8 ± 0.4 vs 2.8 ± 0.4 IU/L) between the two nights. Poisson process modeling demonstrated that the accumulation of deep sleep in the 20 minutes before an LH pulse, whether consolidated or fragmented, was a significant predictor of LH pulse onset (P < .001). CONCLUSION: In pubertal children, nocturnal LH augmentation and pulse patterning are resistant to deep sleep fragmentation. These data suggest that, even when fragmented, deep sleep is strongly related to activation of the GnRH pulse generator.

Evidence that increased ovarian aromatase activity and expression account for higher estradiol levels in African American compared with Caucasian women.

CONTEXT: Serum estradiol levels are significantly higher across the menstrual cycle in African American (AAW) compared with Caucasian women (CW) in the presence of similar FSH levels, yet the mechanism underlying this disparity is unknown. OBJECTIVE: The objective of the study was to determine whether higher estradiol levels in AAW are due to increased granulosa cell aromatase mRNA expression and activity. DESIGN: The design of the study included daily blood sampling and dominant follicle aspirations at an academic medical center during a natural menstrual cycle. SUBJECTS: Healthy, normal cycling AAW (n = 15) and CW (n = 14) aged 19-34 years participated in the study. MAIN OUTCOME MEASURES: Hormone levels in peripheral blood and follicular fluid (FF) aspirates and aromatase and FSH receptor mRNA expression in granulosa cells were measured. RESULTS: AAW had higher FF estradiol [1713.0 (1144.5-2032.5) vs 994.5 (647.3-1426.5) ng/mL; median (interquartile range); P < .001] and estrone [76.9 (36.6-173.4) vs 28.8 (22.5-42.1) ng/mL; P < .001] levels than CW, independent of follicle size. AAW also had lower FF androstenedione to estrone (7 ± 1.8 vs 15.8 ± 4.1; mean ± SE; P = .04) and T to estradiol (0.01 ± 0.002 vs 0.02 ± 0.005; P = .03) ratios, indicating enhanced ovarian aromatase activity. There was a 5-fold increase in granulosa cell aromatase mRNA expression in AAW compared with CW (P < .001) with no difference in expression of FSH receptor. FSH, inhibin A, inhibin B, and AMH levels were not different in AAW and CW. CONCLUSIONS: Increased ovarian aromatase mRNA expression, higher FF estradiol levels, and decreased FF androgen to estrogen ratios in AAW compared with CW provide compelling evidence that racial differences in ovarian aromatase activity contribute to higher levels of estradiol in AAW across the menstrual cycle. The absence of differences in FSH, FSH receptor expression, and AMH suggest that population-specific genetic variation in CYP19, the gene encoding aromatase, or in factors affecting its expression should be sought.

Global consensus statement on menopausal hormone therapy.

The following Consensus Statement is endorsed by The American Society for Reproductive Medicine, The Asia Pacific Menopause Federation, The Endocrine Society, The European Menopause and Andropause Society, The International Menopause Society, The International Osteoporosis Foundation and The North American Menopause Society.

A novel HLA-A*30 allele, HLA-A*30:36.

A novel HLA allele, HLA-A*30:36, is found in a donor from the Central German Bone Marrow Donor Registry.

Gonadotropin responses to estrogen-positive and -negative feedback are identical in African-American and Caucasian women.

CONTEXT: Gonadotropin levels are similar in African-American women (AAW) and Caucasian women (CW), despite higher preovulatory estradiol (E2) levels in AAW, suggesting that AAW may be less sensitive to E2 feedback than CW. OBJECTIVE: The aim of the study was to determine whether responsivity to estrogen feedback differs in AAW and CW. DESIGN AND SETTING: Subjects were studied in the early follicular phase using a 5-d, graded E2 and progesterone infusion. SUBJECTS: Healthy, normal-cycling AAW (n = 10) and CW (n = 13) aged 23-30 yr participated in the study. MAIN OUTCOME MEASURES: Blood samples were collected every 4 h and assayed for LH, FSH, E2, and progesterone. RESULTS: There was no difference in E2-negative feedback on LH (nadir, 3.8 ± 0.4 vs. 5.4 ± 0.9 IU/liter; time of nadir, 33.2 ± 3.3 vs. 32.3 ± 2.7 h) or FSH (nadir, 3.1 ± 0.4 vs. 3.1 ± 0.3 IU/liter; time of nadir, 48.8 ± 2.7 vs. 50.5 ± 3.1 h) in AAW compared to CW. The two groups also demonstrated similar positive feedback responses of E2 on LH (peak, 80.3 ± 13.3 vs. 73.1 ± 11.6 IU/liter; time of peak, 80.4 ± 4.3 vs. 86.5 ± 3.1 h) and FSH (peak, 13.4 ± 1.4 vs. 10.2 ± 1.0 IU/liter; time of peak, 82.2 ± 4.0 vs. 97.2 ± 4.9 h). CONCLUSIONS: LH and FSH feedback responses to a controlled steroid infusion do not differ between AAW and CW, indicating that AAW do not have diminished hypothalamic-pituitary responsivity to E2. These studies support the concept of a threshold effect of E2 in generating LH-positive feedback, suggest pituitary insensitivity to differences in E2 of the magnitude observed in prior studies, and account for similarities in gonadotropins despite E2 differences in AAW compared with CW.

Estrogen levels are higher across the menstrual cycle in African-American women compared with Caucasian women.

CONTEXT: Previous studies have suggested that estrogen levels may be higher in African-American women (AAW) compared with Caucasian women (CW), but none have systematically examined estrogen secretion across the menstrual cycle or in relation to other reproductive hormones. OBJECTIVE: The objective of the study was to compare estradiol (E2), progesterone (P), gonadotropins, androstenedione (a'dione), inhibins, and SHBG levels between AAW and CW across the menstrual cycle. DESIGN, SETTING, AND SUBJECTS: Daily blood samples were collected from regularly cycling AAW (n = 27) and CW (n = 27) for a full menstrual cycle, and serial ultrasounds were performed. MAIN OUTCOME MEASURES: Comparison of E2, P, LH, FSH, SHBG, inhibin A, inhibin B, and a'dione levels. RESULTS: AAW and CW were of similar age (27.2 ± 0.6 yr, mean ± sem) and body mass index (22.7 ± 0.4 kg/m(2)). All subjects grew a single dominant follicle and had comparable cycle (25-35 d) and follicular phase (11-24 d) lengths. E2 levels were significantly higher in AAW compared with CW (P = 0.02) with the most pronounced differences in the late follicular phase (225.2 ± 14.4 vs. 191.5 ± 10.2 pg/ml; P = 0.02), midluteal phase (211.9 ± 22.2 vs.150.8 ± 9.9, P < 0.001), and late luteal phase (144.4 ± 13.2 vs. 103.5 ± 8.5, P = 0.01). Although LH, FSH, inhibins A and B, P, a'dione, and SHBG were not different between the two groups, the a'dione to E2 ratio was lower in AAW (P < 0.001). CONCLUSIONS: Estradiol is higher in AAW compared with CW across the menstrual cycle. Higher estradiol in the face of similar androstenedione and FSH levels suggests enhanced aromatase activity in AAW. Such differences may contribute to racial disparities in bone mineral density, breast cancer, and uterine leiomyomas.

Differential effects of aging on estrogen negative and positive feedback.

Recent studies have demonstrated an age-related decline in gonadotropins and a decrease in pituitary responsiveness to GnRH, indicating that aging influences the neuroendocrine components of the female reproductive axis independently of changes in ovarian function. To determine whether aging might also affect the luteinizing hormone (LH) negative and positive feedback responses to gonadal steroids, we administered a controlled, graded sex steroid infusion to 11 younger (45-56 yr) and nine older (70-80 yr) postmenopausal women (PMW) in whom endogenous ovarian steroids and peptides are uniformly low. The doses of estradiol (E(2)) and progesterone (P) were chosen to mimic levels across the normal follicular phase and have been shown previously to induce negative followed by positive feedback on LH. Similar E(2) and P levels were achieved in younger and older PMW (P = 0.4 and 0.3, respectively) and produced a biphasic LH response in all subjects. The early decline in LH to 53% of baseline was not different in older vs. younger PMW. However, the positive feedback effect was attenuated in older compared with younger PMW (peak LH 144.4 ± 19.5 vs. 226.8 ± 22.3 IU/l, respectively, P = 0.01). In conclusion, these studies in PMW demonstrate preservation of short-term steroid negative and positive feedback in response to exogenous E(2) and P with aging. Attenuation of positive feedback in older compared with younger PMW is consistent with previous reports of declining GnRH responsiveness with aging.

Assessment of thrombin generation measured before and after cardiopulmonary bypass surgery and its association with postoperative bleeding.

BACKGROUND: Bleeding after cardiopulmonary bypass (CPB) is a major cause of morbidity and mortality and consumes large amounts of blood. Identifying patients at increased risk of bleeding secondary to hemostatic impairment may improve clinical outcomes by allowing early intervention. METHODS: This present study recruited 77 patients undergoing CPB and measured coagulation screens, coagulation factors, TEG(®), Rotem(®) and thrombin generation (TG) before surgery and 30 min after heparin reversal. The tests were analyzed to investigate whether they identified patients at increased risk of excess bleeding (defined as > 1000 mL) in the first 24 h postoperatively. RESULTS: Patients who bled > 1000 mL had a lower: platelet count (P < 0.02), factors (F)IX, X and XI (P < 0.005), endogenous thrombin potential (ETP) and an initial rate of TG (P < 0.02) and higher activated partial thromboplastin time (aPTT) (P < 0.001) than patients who bled < 1000 mL. Receiver operating characteristic (ROC) analysis was significant for post-operative TG and aPTT (P < 0.001). Furthermore, reduced pre-operative TG was associated with increased postoperative bleeding (P < 0.02). Pre- and postoperative TG were correlated (ρ = 0.7, P < 0.001). TEG(®), Rotem(®) and prothrombin time (PT) at either time point were not associated with increased bleeding. CONCLUSION: These data suggest that pre-operative defects in the propagation phase of hemostasis are exacerbated during CPB, contributing to bleeding post-CPB. TG taken both pre- and postoperatively could potentially be used to identify patients at an increased risk of bleeding post-CPB.

Estrogen negative feedback on gonadotropin secretion: evidence for a direct pituitary effect in women.

CONTEXT: Studies in humans and animals indicate that estrogen negative feedback occurs at the level of the hypothalamus, but it is unclear whether estrogen also exerts an inhibitory effect directly at the pituitary. OBJECTIVES: The aim of the study was to determine whether estrogen has a direct negative feedback effect at the pituitary and whether this varies with aging. DESIGN AND SETTING: A GnRH antagonist and graded doses of GnRH were used to isolate pituitary responsiveness before and after estrogen administration in Clinical Research Center studies at an academic medical center. SUBJECTS: Subjects were healthy postmenopausal women aged 48-56 yr (n = 8) or 70-75 yr (n= 8). INTERVENTIONS: A suppressive dose of the NAL-GLU GnRH antagonist was administered, followed by graded doses of GnRH before and after 1 month of estrogen administration. RESULTS: LH and FSH responses to GnRH decreased after estrogen administration (P = 0.01 and P = 0.0001, respectively). The ratio of FSH to LH amplitudes decreased in response to estrogen (P = 0.04) indicating a greater sensitivity of FSH than LH to inhibition by estrogen. The inhibitory effect of estrogen on FSH was attenuated with aging (P = 0.02), but was maintained for LH (P = 0.4). CONCLUSIONS: Studies that control for endogenous GnRH and estradiol demonstrate a direct pituitary site of estrogen negative feedback on LH and FSH responsiveness to GnRH in women. The effect of estrogen on FSH responsiveness is greater than on LH and is attenuated with aging. These studies indicate that estrogen negative feedback occurs directly at the pituitary and contributes to the differential regulation of FSH and LH secretion.

Criteria for polycystic ovarian morphology in polycystic ovary syndrome as a function of age.

CONCEPT: Ovaries meeting criteria for polycystic ovary morphology during peak reproductive years may no longer meet the criteria with age. OBJECTIVE: Ovarian volume and follicle number decrease with age in women with polycystic ovary syndrome (PCOS), permitting age-dependent criteria for PCOM. DESIGN AND SETTING: We conducted longitudinal (7-15 year interval) and cross-sectional studies to examine polycystic ovarian morphology over time at an outpatient clinic and pathology laboratory in a tertiary care hospital. PATIENTS: Subjects included those with PCOS defined by the National Institutes of Health criteria (n = 11 and 483 for longitudinal and cross-sectional, respectively) and control women with regular menstrual cycles and no hyperandrogenism (n = 15 and 367), age 18-64 yr. INTERVENTIONS: Subjects underwent an ovarian ultrasound by a single observer. MAIN OUTCOME MEASURES: Ovarian volume and follicle number were measured and ultrasound findings confirmed by a pathologist in a subset (n = 9). RESULTS: Ovarian volume (15.2 +/- 7.4 vs. 7.1 +/- 3.7 ml; P < 0.01) and follicle number (12.8 +/- 3.2 vs. 8.1 +/- 3.9; P < 0.05) decreased longitudinally in PCOS and control women (volume 11.6 +/- 4.4 vs. 5.4 +/- 2.2 ml and follicle number 8.3 +/- 1.9 vs. 6.3 +/- 1.8; both P < 0.005). Using cross-sectional data, log ovarian volume and follicle number decreased in both groups, but the decrease in log ovarian volume was less pronounced in women with PCOS than in controls (P < 0.01). A combination of age, log ovarian volume, follicle number, and testosterone distinguished PCOS subjects from controls with a receiver operator characteristic curve area of 0.90. CONCLUSIONS: Ovarian volume and follicle number decrease with age in women with PCOS and controls necessitating age-based criteria to define polycystic ovarian morphology. It is possible to use these criteria to distinguish PCOS in women over age 40 yr.

The effect of dobutamine on blood flow of free tissue transfer flaps during head and neck reconstructive surgery*.

SUMMARY: In view of the controversy over the use of inotropes in free tissue transfer surgery, we assessed the effect of different intra-operative dobutamine infusion rates on blood flow in the anastomosed recipient artery. Twenty patients undergoing head and neck tumour resection and immediate reconstructive surgery with free tissue transfer were recruited. After completion of the microvascular anastomoses, patients received dobutamine infusions of 2, 4 and 6 microg x kg(-1) x min(-1) in a randomised order. After steady state dobutamine concentration was achieved, mean and maximum blood flow in the arterial anastomosis was measured at each concentration, using the Medi-Stim Butterfly Flowmeter system. Systemic haemodynamic parameters were simultaneously recorded using a pulse contour cardiac output system. Both mean and maximum blood flow increased significantly in the anastomosed artery at dobutamine infusions of 4 and 6 microg x kg(-1) x min(-1) and this was accompanied by increased cardiac output. This may improve free flap perfusion.

Minimum and optimum light requirements for laryngoscopy in paediatric anaesthesia: a manikin study.

Direct laryngoscopy is performed regularly in paediatric anaesthetic practice for the purpose of intubating a patient's trachea. A minimum illumination of 700 lux at a distance of 20 mm has been suggested in a draft standard for laryngoscopes from the International Organization for Standardization. We investigated the minimum and optimum illumination required by anaesthetists during laryngoscopy. Fifty anaesthetists were recruited to perform laryngoscopy on a child manikin with a selection of laryngoscope blades and bulbs attached to a variable voltage supply. There was a large variation in the illumination range of different bulb and blade combinations. We demonstrated a large interindividual variability between anaesthetists for illumination requirements during laryngoscopy. Anaesthetists can see the larynx at very low light levels, but optimum illumination was significantly greater than minimum illumination. Two of the six combinations could produce more than 700 lux. In all, 78% and 54% of anaesthetists considered 700 lux too bright with a halogen and xenon bulb, respectively. Our study suggests that the proposed standard of 700 lux may possibly be too bright.

User satisfaction and forces generated during laryngoscopy using disposable Miller blades: a manikin study.

Increasing awareness of prion-related diseases has led to an increase in the number of disposable laryngoscope blades available. We compared 11 disposable and standard re-usable Miller size 1 blades. In this manikin-based study, we studied user satisfaction for field of view at laryngoscopy, build quality and users' willingness to use the blade in an emergency situation. These were found to be better with metal disposable blades (p

Comparison of the analgesic efficacy and respiratory effects of morphine, tramadol and codeine after craniotomy.

Pain after craniotomy remains a significant problem. The effect of morphine and tramadol patient-controlled analgesia (PCA) on arterial carbon dioxide tension is unknown in patients having such surgery. Sixty craniotomy patients were randomly allocated to receive morphine PCA, tramadol PCA or codeine phosphate 60 mg intramuscularly. Baseline values of pain score (0-10), sedation and arterial carbon dioxide tension were recorded at the time of first analgesic administration and at 30 min, 1, 4, 8, 12, 18 and 24 h. Patient satisfaction was assessed at 24 h. There were no differences in arterial carbon dioxide tension or sedation between groups at any time, but in all three groups some patients had rises greater than 1 kPa. Morphine produced significantly better analgesia than tramadol at all time points (p < 0.005) and better analgesia than codeine at 4, 12 and 18 h. Patients were more satisfied with morphine than with codeine or tramadol (p < 0.001). Vomiting and retching occurred in 50% of patients with tramadol, compared with 20% with morphine and 29% with codeine.

Predictive value of IL-18 and SC5b-9 for neurocognitive dysfunction after cardiopulmonary bypass.

BACKGROUND: Neurological injury after cardiopulmonary bypass (CPB) continues to be a major problem after cardiac surgery. The aim of this study was to investigate the predictive value of Interleukin-18 (IL-18) and SC5b-9 as biochemical markers of neurocognitive dysfunction after cardiac surgery. METHODS: A total of 30 patients undergoing elective cardiac surgery using CPB were recruited. Blood samples were obtained for IL-18 and SC5b-9 concentrations before induction, 24, 48, 72, 96 and 120 h post-CPB and 6 weeks after operation. In addition, patients underwent a standard battery of neuropsychometric tests before operation and at day 5 and 6 weeks after operation. RESULTS: Serum concentration of IL-18, but not SC5b-9, was significantly different between patients with and without neurocognitive dysfunction; serum IL-18 concentration significantly increased in patients with neurocognitive dysfunction (P = 0.018). Neurological outcome was significantly dependent on peak difference in IL-18 concentration at day 5 (P = 0.033), but not on peak difference in SC5b-9 concentration (P = 0.16). Eight patients had neurocognitive dysfunction at day 5 and three had neurocognitive dysfunction at 6 weeks. In a very small number of patients, no significant association was demonstrated between IL-18 or SC5b-9 concentrations and neurocognitive dysfunction at 6 weeks. CONCLUSIONS: IL-18 has the potential as a useful marker of neurological dysfunction, requiring further investigation.

Assessing the efficacy of HME filters at preventing contamination of breathing systems.

Breathing system filters are intended to prevent cross-infection during anaesthesia. However, there is a lack of information on whether filters prevent contamination of the breathing system by the patient. We measured the contamination of 235 used filters of four different types obtained from operating theatres: two pleated hydrophobic (BB25M and BB22/15M, Pall Medical, Portsmouth, UK) used for adult patients and two electrostatic (355/5430 Hygroboy and 355/5427 Hygrobaby, Tyco Healthcare, Gosport, UK) used for paediatric patients. The filters were swabbed over their internal surfaces on both the patient and the machine sides and these were assessed with the use of adenosine triphosphate bioluminescence. Contamination was present on the machine side of 20 (9%) filters. Current standards for testing of filters has no set "pass" level and is performed in the laboratory setting. Bioluminescence may be used in the clinical setting to elucidate factors that might increase the chance of cross-contamination between patients.

Polycystic ovarian morphology in normal women does not predict the development of polycystic ovary syndrome.

CONTEXT: Polycystic ovarian morphology (PCOM) is present in 25% of normal women in the absence of polycystic ovary syndrome (PCOS); however, the natural history of PCOM is unknown. OBJECTIVE: We hypothesized that the presence of PCOM predisposes the development of PCOS. DESIGN: The study was a longitudinal follow-up study over 8.2 +/- 5.2 yr (mean +/- sd; range 1.7-17.5 yr). SETTING: The study took place in an outpatient setting. SUBJECTS: Women who took part in a previous study as a normal control and had an ultrasound examination (n = 40) participated. INTERVENTION: Subjects underwent an interval menstrual history, physical exam, blood sampling, and repeat ultrasound in the follicular phase. MAIN OUTCOME MEASURE: Development of PCOS was diagnosed by irregular menses and hyperandrogenism, in the absence of other disorders. Changes in ovarian morphology over time were evaluated. RESULTS: At the baseline visit, 23 women (57.5%) had PCOM and 17 (42.5%) had normal ovarian morphology. One subject with PCOM developed irregular menses and presumptive PCOS. Eleven subjects with PCOM no longer met the criteria for PCOM at follow-up. There was no factor that predicted the change to normal ovarian morphology at the follow-up visit. CONCLUSIONS: These data suggest that PCOM in women with regular ovulatory cycles does not commonly predispose the development of PCOS. Although it is unusual to develop PCOM if the ovaries are normal on first assessment, ovaries in women with PCOM no longer meet the criteria for PCOM in approximately half of cases over time.

Control of estradiol secretion in reproductive ageing.

BACKGROUND: Estradiol (E(2)) concentration is preserved in older reproductive-aged women despite a decrease in follicle number and androstenedione (AD) levels. We hypothesized that increased aromatase activity accounts for E(2) preservation in older women. METHODS: Older (36-46 years; n = 11) and younger (21-35 years; n = 10) women with 25- to 35-day menstrual cycles participated in a parallel design study. Daily blood samples were drawn starting at menses, and recombinant human FSH (rhFSH), 150 IU, was administered when the dominant follicle's diameter was > or =16 mm. FSH, LH, E(2), estrone (E(1)), AD and the AD/E(1) ratio were compared. RESULTS: E(2) and E(1) concentrations and the E(1)/E(2) ratio were similar across the follicular phase in older compared with younger women, whereas AD and the AD/E(1) ratio were lower. Older women had higher FSH concentrations in the early follicular phase and fewer small follicles. RhFSH-stimulated changes in E(1) were similar between older and younger subjects despite the smaller number of follicles. CONCLUSIONS: These findings suggest that E(2) secretion is maintained by increased aromatase function in older compared with younger reproductive-aged women, whereas there is no apparent difference in 17beta-hydroxysteroid dehydrogenase activity. The increased aromatase is probably driven by increased FSH in the early follicular phase and compensates for the decreased follicle number in older reproductive-aged women.