Thermoacoustic range verification using a clinical ultrasound array provides perfectly co-registered overlay of the Bragg peak onto an ultrasound image.

The potential of particle therapy due to focused dose deposition in the Bragg peak has not yet been fully realized due to inaccuracies in range verification. The purpose of this work was to correlate the Bragg peak location with target structure, by overlaying the location of the Bragg peak onto a standard ultrasound image. Pulsed delivery of 50 MeV protons was accomplished by a fast chopper installed between the ion source and the cyclotron inflector. The chopper limited the train of bunches so that 2 Gy were delivered in [Formula: see text]. The ion pulse generated thermoacoustic pulses that were detected by a cardiac ultrasound array, which also produced a grayscale ultrasound image. A filtered backprojection algorithm focused the received signal to the Bragg peak location with perfect co-registration to the ultrasound images. Data was collected in a room temperature water bath and gelatin phantom with a cavity designed to mimic the intestine, in which gas pockets can displace the Bragg peak. Phantom experiments performed with the cavity both empty and filled with olive oil confirmed that displacement of the Bragg peak due to anatomical change could be detected. Thermoacoustic range measurements in the waterbath agreed with Monte Carlo simulation within 1.2 mm. In the phantom, thermoacoustic range estimates and first-order range estimates from CT images agreed to within 1.5 mm.

Glucoregulatory endocrine responses to intermittent exercise of different intensities: plasma changes in a pancreatic beta-cell peptide, amylin.

Amylin, a peptide hormone released from the beta cells of the pancreas and cosecreted with insulin, is reported to inhibit the release of postprandial glucagon and insulin and to modulate gastric emptying. Changes in insulin and glucagon are important for controlling blood glucose levels under conditions in which metabolic rate is elevated, such as during and following exercise. Amylin may participate in the regulation of blood glucose levels in response to exercise, although the role of amylin has not been investigated. The purpose of the study was to determine the effects of a progressive, intermittent exercise protocol on amylin concentrations and to compare its response to circulating levels of insulin, glucagon, cortisol, and glucose. Seven well-trained males completed an intermittent exercise trial on a treadmill at four progressive exercise intensities: 60%, 75%, 90%, and 100% of maximum oxygen consumption (.VO(2)max). Blood samples were collected before exercise, after each exercise intensity, and for 1 hour following the exercise protocol. Subjects also completed a control trial with no exercise. Amylin and insulin rose from baseline (5.79 +/-.78 pmol/L and 4.76 +/-.88 microIU/mL) to peak after 100% .VO(2)max (9.16 +/- 1.35 pmol/L and 14.37 +/- microIU/ml), respectively and remained elevated during much of recovery. Thus, a progressive intermittent exercise protocol of moderate to maximum exercise intensities stimulates increases in amylin levels in well-trained individuals in a similar fashion to that of insulin, whereas glucagon concentrations only increase after the greatest exercise intensity, then quickly decline. Future studies should examine the effects of higher amylin concentrations in exercise recovery on glucoregulation.

Regulation of leptin and leptin receptor in baboon pregnancy: effects of advancing gestation and fetectomy.

Leptin, a product of both adipose tissue and the placental syncytiotrophoblast and a potential regulator of primate conceptus development, increases in the maternal circulation with advancing gestation. This increase may be potentiated by estrogens, which also increase as pregnancy progresses. In the present study adipose tissue was collected from nonpregnant (n = 5) baboons (Papio sp) and in baboons during early (days 58-62; n = 5), mid (days 98--102; n = 5), and late (days 158-162; n = 5) pregnancy (term, approximately 184 days). Additionally, placental estrogen production was inhibited in pregnant baboons by the removal of fetal androgen precursors via fetectomy at midgestation, with tissues collected from fetectomized (n = 5) baboons approximately 60 days later. Leptin, estrogens, and androgens were quantitated in maternal serum by RIA. Leptin (LEP) and leptin receptor (LEP-R(L) and LEP-R(S) isoforms) messenger ribonucleic acids (mRNAs) were quantitated by competitive RT-PCR, and leptin concentrations were determined by RIA in maternal adipose and placental villous tissues. Although LEP transcript abundance in adipose tissues was unchanged as a result of pregnancy or with advancing gestation, the leptin protein level was higher (P < 0.02) in pregnant baboons in early gestation than in nonpregnant baboons and increased with gestational age (P < 0.04). Maternal serum estrogens (estradiol and estrone) and androgens (androstenedione and testosterone) were lower (P < 0.0001) in fetectomized baboons than in intact controls. Serum leptin concentrations were unchanged by fetectomy, but the abundance of LEP mRNA transcripts was lower (P < 0.003) in sc adipose tissue and 3-fold higher (P < 0.05) in placenta. Similarly, the leptin protein level declined (P < 0.05) in sc adipose tissue and increased (P < 0.05) in placenta in fetectomized baboons. Although LEP-R(L) mRNA levels were unchanged after fetectomy, placental LEP-R(S) transcript abundance was lower (P < 0.04) than in pregnancy-intact baboons matched for gestational age. Results suggest that both adipose tissue and the placenta may contribute to maternal hyperleptinemia during normal primate pregnancy. Furthermore, the withdrawal of placental steroids results in the enhanced placental leptin production that is commensurate with a decline in production by sc adipose tissue.

Effect of estrogen on serum DHEA in younger and older women and the relationship of DHEA to adiposity and gender.

This case-controlled study consisted of 2 parts. The objective of part 1 was to determine the relationship between DHEA, body mass index (BMI), and age in young males, young females, and postmenopausal (PM) females. Part 2 examined the effects of estrogen on DHEA by analyzing the relationship between DHEA and age in young females on and off oral contraceptives (OCs) and PM females on and off estrogen or hormone replacement therapy (ERT/HRT). The study was performed at the Obstetrics and Gynecology Clinic, Texas Tech Health Sciences Center-Amarillo, Exercise Physiology Laboratory at Southeastern Louisiana University, and Woman's Health Research Institute, Woman's Hospital, Baton Rouge, LA. Part 1 groups consisted of: (1) young males between the ages of 18 to 40 years; (2) normally cycling females off OCs, ages 18 to 40 years; and (3) PM females older than 40 years not receiving ERT/HRT. Part 2 groups consisted of: (1) normally cycling females on OCs, ages 18 to 40 years;, (2) normally cycling females off OCs, ages 18 to 40 years; (3) PM females 50 years or older not receiving ERT/HRT; and (4) PM females 50 years or older receiving ERT/HRT. The main outcome measure was serum DHEA concentrations. For part 1, there were significant (P <.05) inverse relationships between DHEA and age for young males; young females, off OCs; PM females, no ERT/HRT r = -.44, -.26, and -.25, respectively. There were no significant relationships between DHEA and BMI for any of the groups. DHEA concentrations were significantly higher in young males than young females even after accounting for age. For part 2, DHEA concentrations were significantly higher in young females off OCs compared with young females on OCs, and significantly higher in PM women off ERT/HRT than those on ERT\HRT. There were significant inverse relationships between DHEA and age for young females and PM females on and off ERT/HRT. From these findings, we conclude that there is an inverse relationship between DHEA and age for young males, young females off OCs, and PM females, no ERT/HRT. No relationship between BMI and DHEA was observed in these same 3 groups. These results agree with previous findings in young men, but differ from previous findings in obese young females. The data also suggest that estrogen treatment (OCs and ERT/HRT) suppresses DHEA concentrations in premenopausal and PM females, and that DHEA declines with age in PM females regardless of estrogen treatment.

Leptin and steroid hormone responses to exercise in adolescent female runners over a 7-week season.

The purpose of the study was to investigate the responses of leptin and steroid hormones to maximal exercise in adolescent female runners over a competitive season. Seven adolescent female distance runners completed three testing trials during weeks 1.4 and 7 of their high-school track season. Blood samples were collected before and after a discontinuous graded exercise test to exhaustion (GXT) for each trial. Tests were administered during the subjects' normal training time (3:30 p.m.-5:00 p.m.). Compared to week 1, peak O2 uptake rose significantly during the season and was 10% and 7% higher at weeks 4 and 7, respectively. Levels of dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEAS), cortisol, testosterone, and leptin increased significantly in response to the graded exercise tests. Testosterone levels were also changed over the course of the study. Resting testosterone levels and testosterone responses to exercise in weeks 4 and 7 were both higher than in week 1. Resting concentrations and acute increases of the other hormones were not changed over the season. It appears, therefore, that DHEA, DHEAS, cortisol, testosterone and leptin concentrations increase in response to running in adolescent female runners. Data also suggest that training and/or maturation increases resting testosterone concentrations and testosterone responses to running in adolescent female runners during a training season.

Serum leptin concentrations and expression of leptin transcripts in placental trophoblast with advancing baboon pregnancy.

Leptin is a polypeptide hormone originally thought to be produced exclusively by adipocytes. Recently, however, both leptin messenger ribonucleic acid (mRNA) and leptin protein were identified in human placental trophoblast cells, suggesting a potential role in primate pregnancy. In the present study, venous blood samples were collected at 5-day intervals during gestation from baboons (Papio sp), an established model for the study of human pregnancy, as well as from nonpregnant baboons, and leptin concentrations were determined by RIA. Additionally, placental villous tissue was collected upon cesarean delivery at early (days 60-62; n = 5), mid (days 98-102; n = 5), and late (days 159-167; n = 5) gestation (term = approximately 184 days), and leptin mRNA was quantitated by competitive RT-PCR. Finally, in situ hybridization was employed to localize transcripts to specific placental cell types. Results determined that maternal leptin levels (mean +/- SEM), which were dramatically greater (P<0.01) than those in nonpregnant cycling baboons (1.4+/-0.1 ng/mL), increased (P<0.005) with gestational age from 63.6+/-10.4 ng/mL on day 60 of gestation to 157.8+/-16.1 near term. Levels declined to those found in cycling baboons by 15 days postdelivery. In contrast to maternal leptin concentrations, placental leptin mRNA decreased (P<0.02) with advancing pregnancy, as transcript abundance declined approximately 8-fold from early to late gestation. Maternal peripheral leptin concentrations were positively correlated (r = 0.66; P<0.001) whereas placental leptin mRNA levels were negatively correlated (r = -0.64; P<0.01) with gestational age. Expression of leptin mRNA transcripts, as evidenced by RT-PCR in villous tissue, was localized principally within syncytiotrophoblast by in situ hybridization. In summary, changes in maternal peripheral leptin concentrations and placental leptin mRNA abundance that occur commensurate with advancing gestational age may imply evolving roles for the polypeptide with advancing primate pregnancy. In this capacity, localization of leptin transcripts within the baboon syncytiotrophoblast suggests the potential for autocrine or paracrine interactions within this endocrinologically active tissue. Finally, both the similarities in leptin ontogeny in baboon and human pregnancy and the singular enhancement of maternal leptin levels inherent throughout baboon gestation emphasize the potential of this nonhuman primate model for the study of leptin action in the maternal-fetoplacental unit.

Serum leptin concentrations in response to acute exercise in postmenopausal women with and without hormone replacement therapy.

The purpose of the study was to examine the effects of acute exercise and hormone replacement therapy on serum leptin concentrations in postmenopausal women. Subjects were 15 healthy, postmenopausal women, 8 on hormone replacement therapy (HRT) and 7 not on hormone replacement therapy (NHRT). Group comparisons indicated no significant differences between HRT and NHRT groups with respect to age, height, weight, BMI, sum of skinfolds, or VO2max, and verified significant differences in estradiol and FSH concentrations. After an overnight fast, each subject completed 30 min of treadmill exercise at approximately 80% VO2max. Over 2 hr and 10 min, baseline, exercise, and recovery blood samples were collected from an intravenous catheter. A control session conducted a month later consisted of the same blood sampling protocol without exercise. Leptin concentrations declined significantly over the course of both the exercise and control sessions, gradually decreasing from baseline levels to -1.54 +/- 0.49 ng. ml-1 postexercise, and continuing to decline to a low of -2.89 +/- 0.59 ng. ml-1 at the end of the session. There was no significant difference between groups with respect to this decline. This is the first study to document that diurnal changes in leptin concentrations in postmenopausal women are not altered by acute treadmill exercise or HRT status. The study underscores the need to account for a diurnal reduction in leptin over the course of an exercise trial.

Late luteal rescue in the baboon (Papio cynocephalus).

Numerous studies have used human chorionic gonadotrophin (HCG) administration to study the response of the primate ovary to gonadotrophin stimulation. These studies are generally performed in the luteal phase with very few studies of the follicular phase. We have studied the effect of both HCG and gonadotrophin releasing hormone (GnRH) agonist administered at the early follicular phase in normally cycling baboons (Papio cynocephalus). Five baboons were treated with increasing doses of HCG for 5 consecutive days starting on day 1 of the cycle and three untreated baboons served as controls. Follicular and luteal phase lengths were determined and serum samples were assayed for progesterone, oestradiol and 17alpha-OH progesterone. In a separate study, six baboons were treated with GnRH agonist (WY-40972) on days 2-6 of the cycle and saline-treated baboons served as controls (n = 5). Mean peak progesterone concentrations (+/- SE) during the treatment interval were 3.88+/-0.56 ng/ml in HCG-treated baboons compared to 0.19+/-0.07 ng/ml in controls (P < 0.001). A similar significant increase (P < 0.001) in serum 17alpha-OH progesterone concentrations was also observed (6.13+/-1.12 ng/ml versus 1.13+/-0.49 ng/ml). In association with the increase in luteal steroids there was also a significant prolongation of menstrual cycle length from 32.7+/-1.2 days in controls to 46.8+/-4.9 days in HCG-treated baboons (P < 0.05), which involved prolongation of the follicular phase (16.7+/-1.2 days to 29.0+/-4.6 days; P < 0.05) with no difference in luteal phase length or progesterone concentrations. In GnRH agonist-treated baboons, mean (+/- SE) cycle length was prolonged to 46.3+/-1.6 days and in saline-treated controls was 32.8+/-0.8 days (P < 0.001), again this was completely represented by the change in follicular phase length, from 13.4+/-0.7 days in controls to 27.2+/-2.1 days in agonist-treated baboons (P < 0.001). In contrast, there was no significant difference in luteal phase length between these two groups (19.4+/-0.7 versus 19.2+/-1.0 days). The prolongation of the follicular phase was accompanied by significant increases in both progesterone (P < 0.01) and oestradiol (P < 0.01) during GnRH agonist treatment above control concentrations. Luteal phase concentrations of these hormones were not different from controls. These results demonstrate the previously unreported finding that gonadotropin stimulation will rescue the corpus luteum in the next follicular phase.

Serum leptin concentration in women: effect of age, obesity, and estrogen administration.

OBJECTIVE: To compare serum leptin levels in normally cycling reproductive females (20-35 years old) with those in age-matched males, in women who were receiving oral contraceptives, and in older (postmenopausal) women (50-65 years old) who were or who were not receiving hormone replacement therapy. DESIGN: Case-control study. SETTING: Obstetrics and Gynecology Clinic, Texas Tech University Health Sciences Center-Amarillo, or the Exercise Physiology Laboratory at Southeastern Louisiana University. PATIENT(S): Normally cycling women between the ages of 20-35 years and age-matched controls who were receiving oral contraceptives. Postmenopausal women between the ages of 50-65 years who were or who were not receiving hormone replacement therapy. MAIN OUTCOME MEASURE(S): Serum leptin concentration. RESULT(S): In all groups, serum leptin concentrations were correlated significantly with body mass index. Leptin levels were significantly higher in young women than young men (P <.001), but no other statistically significant differences were found for the other three comparisons. CONCLUSION(S): Serum leptin concentrations expressed as a measure of adiposity (body mass index) are greater in young normally cycling females (20-35 years old) than in age-matched males. There is no difference in levels of serum leptin between young and postmenopausal (50-65 years old) women. Estrogen administration, either in young women who are receiving estrogen-progestin oral contraceptives or in postmenopausal women who are receiving hormone replacement therapy, does not effect serum leptin concentrations.

Maternal serum androgens in human pregnancy: early increases within the cycle of conception.

Previous studies have demonstrated elevations in testosterone and androstenedione initiated within the cycle of conception in pregnant non-human primates, and minimal data in the human support the same picture. In the present study we have investigated a group of patients scheduled for artificial insemination with regular menstrual cycles. For this study all patients provided blood samples at 5 days after the luteinizing hormone (LH) surges and daily through the luteal phase and into early pregnancy (n = 12). Patients who did not become pregnant served as normal controls (n = 9). We have measured 17-hydroxyprogesterone (17-OHP) as a marker of luteal activity not obscured by progesterone within the cycle of conception and testosterone and androstenedione as the major androgens. There were no significant changes in testosterone and androstenedione in the non-pregnant controls, but both testosterone and androstenedione were significantly elevated in the pregnant luteal phase, with the first increases occurring at 15 and 14 days respectively after the LH surge. Three of 12 pregnant patients did not demonstrate a dramatic increase in either testosterone or androstenedione and when examined more carefully a corresponding lack of increase in 17-OHP in those same subjects indicated less than optimal luteal activity, suggesting that these androgens were products of the corpus luteum. In three subjects in which consecutive non-pregnant and pregnant cycles were followed there was a dramatic increase from the non-pregnant luteal phase to the pregnant luteal phase indicating that the more important observation may be the concentrations of androgens in the conceptive luteal phase compared to some baseline, either previous luteal phase or even follicular phase. We have also studied changes in dehydroepiandrosterone sulphate and found that there was no significant contribution to this increase in androgens in early conception. These studies demonstrate a significant increase in both testosterone and androstenedione presumably of ovarian, specifically luteal, origin and that adrenal androgen production is not a factor in these changes.

Rapid, convenient radioimmunoassay of estrone sulfate.

We developed a specific, simple, and rapid RIA for the direct quantification of estrone sulfate (E1S) and established its performance characteristics. The assay has a dynamic range of 0.05-90 micrograms/L with a detection limit of 0.009 microgram/L. Intraassay CVs were 9.2%, 4.5%, and 4.6% at 0.35, 9.0, and 60 micrograms/L, respectively. Interassay CVs were 8.8%, 5.1%, and 5.5% at 0.076, 0.5, and 12 micrograms/L, respectively. Linearity of dilution studies showed values of 80-105% of expected, and recovery of E1S added to serum samples ranged from 82% to 102%. Cross-reactivities with structurally related estrogens were < 5%. When compared with a conventional assay (involving hydrolysis of E1S and indirect measurement of estrone), the present RIA showed excellent correlation (r = 0.99, slope = 1.54, Sy/x = 2.14, n = 71). Mean E1S concentrations measured with this RIA for normal men (n = 20) and women in follicular (n = 20) and luteal (n = 25) phases of their menstrual cycle were 0.96, 0.96, and 1.74 microgram/L, respectively. Mean E1S concentrations for oral contraceptive users (n = 20) and postmenopausal women without hormone replacement therapy (n = 21) or on hormone replacement therapy (n = 22) were 0.74, 0.13, and 2.56 micrograms/L, respectively. Serum concentrations of E1S in pregnant women in their first (n = 14), second (n = 17), and third (n = 15) trimesters were 20, 66, and 105 micrograms/L, respectively. Availability of this simple RIA should provide a useful tool for the assessment of estrogen status in women.

Comparison of three methods for 17 alpha-hydroxyprogesterone.

We compared the performance of three 17 alpha-hydroxyprogesterone kits: the double antibody method, the coated tube method (ACTIVE), both from Diagnostic Systems Laboratories, Inc. (DSL) and the coated tube method (COAT-A-COUNT) from Diagnostic Products Corporation (DPC). The assay performance of the two DSL kits was very similar in terms of sensitivity, intra- and inter-assay precision, linearity of dilution, recovery, and specificity. We also analyzed 190 samples for 17 alpha-hydroxyprogesterone values using the above three kits. Twenty-three subjects were from prepubertal population (ages 1 month-13 years), thirty subjects were normal adult males (ages 20-53 years) and the remaining subjects were females in different phase of menstrual cycle (n = 40), on oral contraceptives (n = 20), post-menopausal (n = 17), or pregnant women in their first, second, or third trimester (n = 60). In addition to these 60 pregnancy samples, we analyzed serial samples from 3 pregnancies. 17 alpha-OHP levels paralleled the progesterone levels in all three kits. Although there was reasonable correlation between the DPC and the two DSL kits, the 17 alpha-OHP values were found to be significantly higher with DPC kit during the 2nd and 3rd trimester of pregnancy indicating probable interference in the DPC assay by some structurally related steroids present during pregnancy. The DSL assays may be particularly well suited for measuring 17 alpha-OHP levels during pregnancy.

Postimplantation increase in plasma fibrinogen concentration with increase in relaxin concentration in pregnant dogs.

OBJECTIVE: To determine time courses of pregnancy-related changes in plasma fibrinogen, serum relaxin, and serum C-reactive protein-like immunoreactivity (CRP-LI) concentrations in pregnant and nonpregnant dogs. ANIMALS: 16 pregnant and 13 nonpregnant Beagles, 6 pregnant Beagles, and 3 pregnant and 3 nonpregnant dogs of other breeds. PROCEDURE: Fibrinogen was measured by nephelometric centrifugal analysis of light scatter in plasma samples of all dogs, and CRP-LI was measured by fluorescence immunoassay in selected sera from 10 pregnant and 10 nonpregnant dogs. Relaxin was measured in selected sera from 7 pregnant and 7 nonpregnant dogs. RESULTS: During pregnancy, fibrinogen concentration increased between days 21 and 30 after the luteinizing hormone surge, and was > 280 mg/dl between days 29 and 50 in 84 of 86 samples, with peak values 539 +/- 29 mg/ dl higher (P < 0.01) than those in nonpregnant dogs (188 +/- 8 mg/dl), higher values from days 21 to 50 (P < 0.01) than those in nonpregnant dogs, and values similar to those in nonpregnant dogs after day 50. Relaxin concentration was increased from days 26 to 30 and 0 to 4 days after fibrinogen concentration increased in pregnant dogs, and was not detectable in nonpregnant dogs. The CRP-LI concentration was higher in pregnant dogs at days 26 to 50, but values were inconsistent within and among dogs, and near the limit of sensitivity of the assay. CONCLUSIONS: Concentration of the acute-phase reactant protein fibrinogen increases after day 20 following implantation in dogs, at or just before the pregnancy-specific increase in relaxin concentration from days 26 to 30, and persists until day 50. CLINICAL RELEVANCE: Fibrinogen assay may be useful for pregnancy diagnosis in dogs.

Evidence for diminished midcycle ovarian androgen production in older reproductive aged women.

OBJECTIVE: To test the hypothesis that reproductive aging is associated with menstrual cycle-related decreases in androgen secretion. DESIGN: Comparison of cross-sectional data. SETTING: University teaching hospital. PATIENTS: Two groups of seven women were studied; midreproductive aged (19 to 37 years old) and older reproductive aged (43 to 47 years old). All patients were cycling regularly and had normal PRL and TSH. INTERVENTIONS: Patients underwent blood sampling during selected days of the menstrual cycle. MAIN OUTCOME MEASURE: After establishing the date of the midcycle surge, specimens were measured on selected days for androstenedione (A), total T, free T, and sex hormone-binding globulin (SHBG) using commercially available reagents. RESULTS: Sex hormone-binding concentrations did not vary across the menstrual cycle and did not differ between older and younger women. Total T did not differ significantly at any cycle stage between older and younger women. However, the midcycle rise in free T and A seen in younger women was consistently and significantly absent in the older women. CONCLUSIONS: In the absence of significant changes in SHBG associated with older reproductive age, the finding of diminished concentrations of both free T and A suggests that these hormones are produced in lesser quantity at midcycle in older women. Because the changes we noted depended on menstrual cycle stage, our findings suggest that an ovarian and not adrenal process is involved.

When is it safe to switch from oral contraceptives to hormonal replacement therapy?

Women may continue to use oral contraceptives (OCs) into their 40's and 50's, but to date no method has been evaluated to ascertain their ovarian status, i.e., whether fertility and estrogen production have diminished sufficiently so they could be safely switched to hormonal replacement therapy. A group of 12 postmenopausal women who had been, for long periods of time, on a regimen of 3 back-to-back packages (i.e., 63 days on, 7 days off) of low-dose oral contraceptives have been studied. Secondly, a group of 9 perimenopausal women aged 36 to 47 were examined in the same manner. The third group consisted of early reproductive age women (arbitrarily divided into subsets aged 17-25 and 26-35 using low-dose OCs in the customary regimen) as normal controls. Blood samples were obtained on the last day of a pill cycle and at 7 days off the pill. In some menopausal women, blood samples were obtained at both 7 and 14 days off OCs. Serum was assayed by RIA for estradiol, FSH and LH. As expected in the young reproductive age women, estradiol levels increase at one week off the pill, together with a rebound in FSH and LH to follicular phase levels. In the perimenopausal group, there was a sharp distinction based on age. The women over 40 showed a more marked rise in FSH while those aged 36-40 showed a distinctly lesser response. Estradiol levels were variable, but tended to show some age grouping. Little diagnostic separation was observed for LH. In postmenopausal women, FSH levels were not always elevated at one week post-pill, and even in a second trial with sampling at one and two weeks off the OC, not all postmenopausal women showed a "menopausal" increase in FSH. The more uniform feature was that estradiol levels never increased above basal values. The study found that serum estradiol levels increase after a week off the pill in controls, but are unchanged at one and two weeks in the menopausal group. FSH levels rebound normally in reproductive age women and usually, but not always, increase substantially in postmenopausal women. After two weeks off OCs, an increased FSH and/or no change in basal estradiol levels is strong evidence that it is now safe (contraceptively speaking) to switch from OCs to standard hormone replacement regimens.

PIP: Women may continue to use oral contraceptives (OC) into their 40s and 50s. No method has, however, been evaluated to determine whether fertility and estrogen production have diminished enough so that they could safely switch to hormonal replacement therapy. The authors studied a group of 12 postmenopausal women who had been, for long periods of time, on a regimen of three back-to-back packages of low-dose OCs, and a group of nine perimenopausal women aged 36-47 years. Women aged 17-25 and 26-35 years using low-dose OCs in the customary regimen were used as normal controls. Blood samples were taken on the last day of a pill cycle and at 7 days off the pill. In some menopausal women, blood samples were obtained at both 7 and 14 days off OCs. Serum was assayed by RIA for estradiol, FSH, and LH. The study found that serum estradiol levels increase after a week off the pill in controls, but are unchanged at one and two weeks in the menopausal group. FSH levels rebound normally in reproductive-age women and usually, but not always, increase substantially in postmenopausal women. After two weeks off OCs, an increased FSH and/or no change in basal estradiol levels is strong evidence that it is now safe to switch from OCs to standard hormone replacement regimens.