Rehabilitation and exercise oncology program: translating research into a model of care.

INTRODUCTION: The Rehabilitation and Exercise Oncology model of care (ActivOnco) was established to optimize cancer survivorship through exercise prescription and active lifestyle promotion, providing a transition of care from hospital to community. Patients having any cancer diagnosis, stage of disease, and treatment were eligible for evaluation and exercise prescription upon deterioration of performance status. The team of professionals included hospital-based physiotherapists proactively screening for rehabilitation needs, loss of functional independence, and exercise eligibility, plus exercise specialists in a community-based Wellness Centre to provide follow-up or direct access for post-treatment or non-complex patients. METHODS: From January 2011 to December 2015, the hospital team assessed 1635 patients representing all major cancer sites, and the Wellness Centre team evaluated and prescribed exercise for 1066 participants. Primary interventions provided were education about fatigue management, physical activity promotion, exercise prescription, fracture risk reduction, referral to specialized follow-up services (for example, occupational therapy, lymphedema clinic), and coordination for mobility aids and paratransit services. RESULTS AND CONCLUSIONS: Implementation of the ActivOnco model of care showed that exercise alone is not a panacea for all functional deterioration associated with the cancer trajectory and its treatment. However, screening to identify rehabilitation needs combined with exercise prescription can effectively improve the quality of survivorship in cancer patients. Program developments are limited by the cost of human resources, lack of hospital-based physical resources, and lack of public funding, all of which significantly limit the scope and development of appropriate services.

Thoracoscopic surgery in the management of pediatric malignancies: a multicentric survey of the Italian Society of Videosurgery in Infancy.

BACKGROUND: Few reports have elucidated the role of minimally invasive surgery (MIS) for pediatric malignancies. This study aimed to review the results of a multicenter study on the management of thoracic tumors in children using MIS. METHODS: A 5-year retrospective review of all MIS procedures for the treatment of pediatric malignancies performed in seven centers belonging to the Italian Society of Videosurgey in Infancy is reported. The data from 145 pediatric oncologic patients (80 girls and 65 boys) ages 30 days to 17 years (median, 7.2 years) were analyzed. Of the procedures performed, 87 were laparoscopies (60%), 55 were thoracoscopies (38%), and 3 were lumboscopies (2%). This study focused only on the results of the 55 thoracoscopic procedures performed for diagnostic purposes in 19 cases (34.6%) and for therapeutic purposes in 36 cases (65.4%). RESULTS: The duration of surgery was 15 to 180 min (median, 65 min). Metastasectomies were performed for various etiologies in 31 of the 55 cases. Of the 55 patients, 5 underwent resection of a mediastinal tumor, and 19 underwent a diagnostic thoracoscopy. During a mean follow-up period of 25.6 months, 2 (3.6%) of the 55 patients experienced perioperative complications. CONCLUSIONS: The role of MIS in tumor resection for children is currently limited, but may be used in individual cases when the preoperative workup shows it to be feasible. Its indication is strictly dependent on the thoracoscopic experience of the surgeon and the tumor site for preoperative imaging techniques. When the indication for thoracoscopy is correct, this approach has high therapeutic applicability (65.4% in our series). Our preliminary experience shows that careful patient selection and an appropriate level of technical skill make thoracoscopy a reasonable and safe option for the treatment of pediatric malignancies.

Italian multicentric survey on laparoscopic spleen surgery in the pediatric population.

BACKGROUND: Some technical aspects of laparoscopic spleen surgery still are debated, although efforts have been made to standardize them. The position of the patient, the approach to the spleen, vessel identification and division, and spleen extraction can vary from center to center. METHODS: This retrospective muticentric study led by the Società Italiana di Videochirurgia Infantile (SIVI) examined indications, surgical details, and complications of laparoscopic spleen surgery in the pediatric population during a 5-year period. RESULTS: The study period from January 1999 to December 2003 (5 years) involved nine centers and included 85 patients with a mean age of 10 years (range, 2-17 years). Hypersplenism or severe hemolysis in cases of hematologic disorders represented the most important indications. More than 90% of the patients underwent total laparoscopic splenectomy. Specific technical details from each center were collected. Intraoperative complications occurred in 19% of the patients (hemorrhage in 8% and technical problems in 14%), and 6% of the patients required conversion to the open approach. No deaths occurred, and no reoperations were required. Postoperative complications were experienced by 2% of the patients. CONCLUSION: Laparoscopic spleen surgery is safe, reliable, and effective in the pediatric population. On the basis of the results, some technical details for laparoscopic spleen surgery can be suggested. The patient is preferably kept supine or lateral, approaching the spleen anteriorly. Moreover, the ilar vessels should be identified selectively and individually, with initial artery division performed to achieve spleen shrinking. Any hemostatic device proved to be effective in experienced hands. Once freed, the spleen is preferably extracted via a suprapubic cosmetic transverse incision (faster, easier, and safer), although a bag can be used. Finally, the size of the spleen does not represent a contraindication for a trained and experienced surgeon. Nevertheless, this parameter must be considered when laparoscopic spleen surgery is planned.

One-trocar transumbilical laparoscopic-assisted management of Meckel's diverticulum in children.

PURPOSE: Transumbilical laparoscopic-assisted intestinal surgery using only "one trocar" is a very minimal invasive procedure. The authors present their experience for the management of Meckel's diverticulum. MATERIALS AND METHODS: Between January 2001 and December 2004, 9 transumbilical laparoscopic-assisted procedures were performed for Meckel's diverticulum. The median age of the patients was 6.1 years (range, 6 months-13.6 years). Six patients were admitted for intestinal bleeding and technetium-99m pertechnetate scan was positive in 3. Three patients had recurrent abdominal pain and abdominal ultrasound scan showed a cystlike structure. An intraumbilical Hasson 10-mm trocar was inserted in an open fashion. Using a 10-mm operative laparoscope, the terminal ileum was grasped with an atraumatic instrument and exteriorized through the umbilicus. Ileal exploration and treatment were performed extracorporeally. RESULTS: Meckel's diverticulum was identified in 8 patients and ileal duplication in 1 patient: intestinal resection/anastomosis (n = 7) or excision of diverticulum (n = 2) was performed. There were no operative complications. Median hospital stay was 4 days (range, 3-7 days). At a median followup of 24 months (range, 3-51 months), all patients are asymptomatic. CONCLUSION: Our results indicate that the one trocar transumbilical laparoscopic-assisted procedure is safe and effective for the diagnosis and treatment of Meckel's diverticulum, with excellent cosmetic results.

Total estradiol, free estradiol, sex hormone-binding globulin, and the fraction of estradiol bound to sex hormone-binding globulin in human follicular fluid.

Sex hormone-binding globulin (SHBG), percent free estradiol (E2), the fraction of E2 bound to SHBG, and total E2 were measured in the serum and follicular fluid of 12 women (25 follicles) who had received gonadotropin stimulation in an in vitro fertilization program. The women were classified as high or low responders based on peak serum E2 levels (high responders: peak E2, greater than 1500 pg/ml; low responders: peak E2, less than 1000 pg/ml). During treatment, serum levels of SHBG increased in high responders from 55 +/- 8.8 (+/- SEM) to 96 +/- 16 nM (P less than 0.01), but did not change in low responders. SHBG was more concentrated in follicular fluids from high responders (142 +/- 12.5 nM) than in those from low responders (44.4 +/- 5.8 nM). A positive correlation was found between serum and follicular fluid levels of SHBG (r = 0.873; P less than 0.01). In follicular fluid, total E2 levels, which varied from 100-2650 ng/ml, correlated (r = 0.790; P less than 0.01) closely with SHBG levels. The percent free E2 averaged 5.9% (range, 4-10.6%) in follicular fluid compared to 1.8% (range, 1.5-2.1%) in serum. An inverse correlation (r = -0.661; P less than 0.01) was found between total E2 concentrations and percent free E2 in follicular fluid. The relationship between serum and follicular fluid levels of SHBG suggests that SHBG in follicles arises from the circulation. Although SHBG is present in follicular fluid in amounts similar to those in serum, the large quantities of E2 in preovulatory follicules exceed the binding capacity for SHBG, and the majority of E2 appears to be bound to albumin. Hence, it seems unlikely that SHBG in follicular fluid regulates estrogen action in ovarian target cells.

Flow cytometric analysis of deoxyribonucleic acid in human granulosa cells from in vitro fertilization cycles: relationships to oocyte maturity and fertilizability and to follicular fluid steroids.

We measured the mitotic activity of granulosa cells, sex steroid concentrations in follicular fluids, and the maturity and fertilizability of oocytes from 49 follicles. Flow cytometric measurements of DNA were used to determine the percentage of cells in G0/G1, S, and G2/M phases of the cell cycle. Mitotic index was designated as the percentage of granulosa cells in S + G2/M. The progesterone concentration and the progesterone to estradiol ratio in follicular fluids were inversely correlated to mitotic index (r = -0.506; P less than 0.001, and r = -0.320; P less than 0.02, respectively). Estradiol and androstenedione levels did not correlate with the mitotic index. The mitotic index was higher in follicles with immature oocytes [25.6 +/- 2.0% (+/- SE); n = 7] than in follicles with mature oocytes (15.6 +/- 1.2%; n = 41; P less than 0.001). The mitotic index of granulosa cells was lowest in follicles with oocytes that fertilized (15.5 +/- 1.8%), higher in follicles with oocytes that remained unfertilized (18.5 +/- 1.3%; P less than 0.03), and highest in follicles with oocytes that fertilized abnormally (24.0 +/- 2.1%; P less than 0.02). Differences in maturity or fertilizability of oocytes were not associated with variations in follicular fluid progesterone concentrations. The study supports the concept that mitotic activity is decreased when granulosa cells become luteinized. During early follicular growth it is assumed that estradiol and perhaps androstenedione may be important regulators of cell division. Our findings suggest that progesterone, perhaps acting as an antiestradiol, is more important in controlling granulosa cell division of preovulatory follicles during the late follicular phase.

Gonadotropin-releasing hormone-dependent chorionic gonadotropin secretion in a menopausal woman.

We report the evaluation of a 46-yr-old asymptomatic menopausal woman whose serum hCG concentrations remained persistently supra-normal for 3 yr (mean +/- SD, 20 +/- 10 IU/L; n = 19). Holo-hCG and beta-core fragments were detected in the patient's urine by Ultragel chromatography, followed by specific RIAs. Trophoblastic, germ cell, and other malignancies appeared to be excluded by the absence of serum tumor markers and imaging procedures of the pelvis, abdomen, breast, and chest. Administration of a single bolus dose of synthetic GnRH (100 micrograms) increased the serum hCG concentration by 50% (from 26 to 40 IU/L). Administration of the Nal-Glu GnRH antagonist (5 mg, sc, every 12 h for 1 week) decreased the serum hCG concentration from 27 to 4.6 IU/L. The pronounced decrease in the serum hCG concentration during antagonism of the action of endogenous GnRH by administration of Nal-Glu GnRH suggests that the pituitary is the source of the supra-normal serum hCG concentrations, because the pituitary is exposed to the highest concentration of endogenous GnRH.

Effect of m-chlorophenylpiperazine on plasma homovanillic acid concentrations in healthy subjects.

In view of the abundant anatomical and functional interactions between serotonin and dopamine systems, this study examined the effect of the serotonin agonist, m-chlorophenylpiperazine (mCPP) on plasma concentrations of the dopamine metabolite, homovanillic acid. Plasma prolactin levels, body temperature, and mCPP blood level were also measured. mCPP (0.35 mg/kg) and placebo were administered orally to 10 healthy men in a randomized double-blind design. Variables were measured for 210 min after administration of capsules. mCPP raised prolactin and temperature as compared to placebo, but did not affect plasma homovanillic acid concentrations. Results suggest that mCPP does not alter dopamine function.

Perioperative complications arising after transvaginal oocyte retrieval.

OBJECTIVE: To determine the incidence of perioperative morbidity in patients undergoing transvaginal oocyte retrieval and to identify those patients at greatest risk for complications. METHODS: A retrospective analysis was performed on 674 patients of reproductive age who underwent transvaginal retrieval of oocytes for assisted reproduction technologies during a 3-year period. All procedures were performed by surgeons with extensive experience with transvaginal retrieval. Patients were entered into the program with a primary diagnosis of unexplained infertility (16%), endometriosis (32%), pelvic adhesions and/or tubal occlusion (38%), or infertility from male or immunologic factors (14%). RESULTS: Of the 674 patients studied, ten (1.5%) required hospital admission because of perioperative complications. Nine of these patients needed intravenous antibiotics and one required admission and observation for an expanding broad-ligament hematoma. Six of nine women admitted for antibiotic therapy had a history of extensive pelvic adhesions with or without a history of salpingitis. Five of nine patients had a history of salpingitis. In addition, two patients experienced impressive vaginal arterial bleeding during the procedure. CONCLUSION: This study suggests that transvaginal retrieval may not be as innocuous as is often expressed and that the primary factor predisposing to perioperative morbidity is a history of previous pelvic inflammatory disease and/or adnexal adhesions.

Incidence of abortion in pregnancies after in vitro fertilization and embryo transfer.

Our purpose was to assess factors that are associated with an increased rate of spontaneous abortion in pregnancies initiated by in vitro fertilization. Pregnancies were diagnosed by measurement of serum human chorionic gonadotropin (hCG) 15 days after embryo transfer. Of the 64 women who conceived, 47 delivered term infants, one patient delivered a stillborn at 22 weeks, 14 aborted in the first trimester, and two had pregnancies that implanted in the tube. Abortion rates were similar for women treated with human menopausal gonadotropin (24%; 12 of 54) and those who received clomiphene citrate (12.5%; one of eight). Two patients conceived after treatment with a combination of clomiphene citrate and human menopausal gonadotropin, neither of whom aborted. In 54 patients treated with human menopausal gonadotropin, there were no significant differences in mean maternal age, number of years of infertility before the pregnancy, history of previous pregnancies, amount of human menopausal gonadotropin used to induce ovulation, serum estradiol levels on the day of hCG administration, mean number of follicles, and the mean number of transferred embryos between the group who delivered and the group who aborted. We conclude that none of these factors are associated with increased tendency for fetal loss in our in vitro fertilization program. Beta-hCG levels on day 15 after embryo transfer were significantly lower in the group who aborted than in the group who delivered, and may be predictive of implantation failure.

A comparison of 10% pentastarch and 5% albumin in patients undergoing open-heart surgery.

Colloids are useful in cardiac surgery to increase preload and improve cardiac output without the risks associated with blood transfusions. Pentastarch is a new low-molecular weight hydroxyethyl starch compound under investigation for this purpose. The authors compared, in a randomized fashion, 12 patients who received pentastarch and 17 patients who received albumin for volume expansion after open-heart surgery. During the 24-hour study period there was no significant difference between the two groups with respect to systemic blood pressure, mean arterial pressure, cardiac index, right atrial pressure, and pulmonary capillary wedge pressure, with the exception of a higher mean arterial pressure and systolic blood pressure at 4 hours in the albumin group and higher heart rate at 12 hours in the pentastarch group. In addition, postoperative prothrombin time, partial thromboplastin time, fibrinogen, platelets, and factor VIII levels were not significantly different between the two groups. There were no complications attributed to colloid administration. The hemodynamic parameters were further evaluated in a subset of 6 pentastarch and 9 albumin patients who received the first 500 mL of colloid in a similar time frame and under similar clinical conditions. The patients who received pentastarch showed a significantly greater increase in cardiac index than did the patients who received albumin. No significant change in other parameters were noted between the two groups. The authors conclude that pentastarch is as safe as albumin and may be a more effective volume expander than albumin when used in open-heart surgery patients.

The role and value, present and future, of ultrasound in the detection of ovulation.

PIP: The use of ultrasounds has recently been extended to the evaluation of ovarian functions. Ultrasounds can detect the presence of one or more developing follicle in the ovary, thus enabling a physician to avoid multiple ovulation in patients under gonadotropin treatment. Ultrasounds may also prove useful for timing of insemination, and for the monitoring of follicular development in patients who are candidates for ovum retrieval and in vitro fertilization. As ultrasounds technology is developed further, it will be possible to substitute it to the direct visualization which is presently essential in the evaluation of the infertile patient.^ieng

Dispensability of fimbriae: ovum pickup by tubal fistulas in the rabbit.

This study was carried out to test the general belief that fimbriae should be considered almost indispensable to ovum capture. Surgical procedures, including resection of the mesotubarium superius and infundibulum tubae together with the creation of a fistula, are described. An attempt to enhance tubal patency by temporarily using estrogens is discussed. Ovum pickup was determined by flushing both tubes and the uterus 2 days following ovulation induction. The prior use of estrogens did not appear to have increased subsequent ovum pickup in control animals; on the contrary, it even seems possible that estrogens had negatively influenced pickup by the fistulas. With five fistulas, however, three recovered ova represented a pickup rate of 7% to 14% of all ova available following one human chorionic gonadotropin-induced ovulation. These figures suggest that ovum pickup by terminal ampullary fistulas is not negligible; they might indicate that absence of fimbriae offers neither good protection against pregnancy following sterilization nor a hopeless prognosis for fimbriectomy reversal when a distal patent tube is present.

Protein composition of human uterine fluid.

Polyacrylamide gel electrophoresis of uterine washings and the corresponding serum from 35 patients revealed the presence of at least four characteristic uterine proteins and large amounts of the serum proteins, albumin and transferrin. The appearance of these characteristic proteins was studied during specific phases of the menstrual cycle. At lease one of the four uterine proteins was observed in postovulatory samples only, with a maximum frequency of occurrence during the midsecretory phase. In contrast, one of these proteins predominated in preovulatory uterine washings while another appeared randomly throughout the menstrual cycle. Substantial variations in protein patterns were observed in patients sampled during different menstrual cycles. The presence of the major antigenic components of serum in uterine washings was confirmed; however, immunochemical demonstration of the existence of uterine-specific antigens was unsuccessful.

Acrosomal proteinase inhibitors in rhesus monkey (Macaca mulatta) oviduct fluid.

PIP: Acrosomal proteinase inhibitors were found in rhesus monkey fallopian tubes. Spermatozoa contain a proteolytic enzyme in their acrosomal heads and which would be adversely affected by the presence of acrosomal proteinase inhibitors. The inhibitor concentration was high before ovulation, decreased to low levels around the time of ovulation, and rose to high levels again within 1-3 days after ovulation. Alpha-1-antitrypsin, alpha-2-macroglobulin and alpha-1-antichymotrypsin all followed this high-low-high pattern. Alpha-1-antitrypsin in human cervical mucus is found to follow a similar waxing and waning according to progesterone secretion.^ieng

Oxygen tension in the oviduct of the rhesus monkey (Macaca mulatta).

The oxygen tension in the oviductal fluid of adult female rhesus monkeys was measured by means of miniaturized, flexible, oxygen probes between days 5 and 22 of the menstrual cycle. In the follicular phase, the value was very low, less than 10 Torr. At the time of ovulation to about 5 to 7 days thereafter, the oxygen tension in the tube on the side of ovulation increased within approximately 2 minutes after insertion of the oxygen probe from the low level to the same value as in the blood. In the contralateral oviduct, the oxygen tension remained at less than 10 Torr. These findings suggest that, in the absence of ovulation, the blood-oxygen supply of the oviduct provides the exact oxygen requirement of oviductal tissue, with no excess oxygen available for the tubal fluid. At and shortly after ovulation, the presence of a probe stimulates, by an unknown mechanism, an increase in the oxygen tension in the oviductal fluid which provides an environment sufficiently well-oxygenated for gamete survival, fertilization, and subsequent further development of the embryo. We suggest that the ovum entering the oviduct provides a similar stimulus with a similar result by the same unknown mechanism.

PIP: The oxygen tension is the oviductal fluid of adult female rhesus monkeys was measured by means of a miniaturized, flexible, oxygen probe between Days 5-22 of the menstrual cycle. In the follicular phase, the value was very low, is less than 10 Torr). At the time of ovulation to about 5-7 days thereafter, the oxygen tension in the tube on the side of ovulation increased within approximately 2 minutes after insertion of the oxygen probe from the low level to the same value as in the blood. In the contralateral oviduct, the oxygen tension remained at is less than 10 Torr. These findings suggest that, in the absence of ovulation, the blood-oxygen supply of the oviduct provides the exact oxygen requirement of oviductal tissue, without excess oxygen available for the tubal fluid. At and shortly after ovulation, the presence of a probe stimulates, by an unknown mechanism, an increase in the oxygen tension in the oviductal fluid which provides an environment sufficiently well-oxgenated for gamete survival, fertilization, and subsequent further development of the embryo. It is suggested that the ovum enteri ng the oviduct provides a similar stimulus with a similar result by the same unknown mechanism.

Hydrogen ion and carbon dioxide content of the oviductal fluid of the rhesus monkey (Macaca mulatta).

The pH in the oviduct lumen of adult female rhesus monkey (Macaca mulatta) during the menstrual cycle was measured by means of miniaturized pH electrodes. Two types were used: one was a flexible electrode 1.4 mm in diameter; the other was a rigid electrode 0.8 mm in diameter. The same results were obtained with both types. For PCO2 measurements, the pH electrodes was converted to a Severinghaus tyep electrode covered with a Teflon membrane. During the follicular phase, the pH remains constant in the range 7.1 to 7.3. In association with ovulation, there is a sudden increase in the pH to the range 7.5 to 7.8. The pH remains high through the luteal phase. The PCO2 values obtained showed no evident changes with day of cycle. The range of values estimated was wide because of drift in electrode calibration, with the average level about 89 Torr, compared with 40 Torr for blood. At the average pH of 7.2 in the follicular phase, this value of PCO2 corresponds to 35 mM HCO3-; at the average pH of 7.6 of the secretory phase, this value corresponds to 90 mM HCO3-. This increase in pH and HCO3- after ovulation would be expected to enhance dispersal of corona cells during fertilization and to provide a favorable environment for the developing embryo.

Differences in ovarian stimulation in human menopausal gonadotropin treated woman may be related to follicle-stimulating hormone accumulation.

Two groups of normal ovulatory women who displayed either a marked (high responders; HR) or a more subtle (low responders; LR) ovarian response to a fixed dose of human menopausal gonadotropins (hMG) were evaluated for differences in blood levels of hormones. Serum follicle-stimulating hormone (FSH) levels doubled during the first 3 days of treatment (to approximately 20 mIU/ml) in all patients; thereafter, the levels plateaued in LR but continued to rise steadily (to 35 mIU/ml) in HR. In the latter group, rise in estradiol (E2) and FSH was accompanied by an increase of luteinizing hormone (LH; two to five times) progesterone (P; four to eight times) testosterone (T; three to four times) and prolactin (PRL; 2 times) toward the end of the follicular phase. Positive correlation was found between FSH and E2 in HR and LR. Positive correlation was found, however, between LH, T, and P and between E2, P, and PRL only in HR. The extent of FSH accumulation in the circulation may be a principal factor in determining an individual's response to hMG therapy. Temporal changes of blood hormones indicated that the continuous rise in FSH levels in HR was associated with early luteinization of the follicles. Increased secretion of P in the follicular phase of these women (HR) probably synergized with the elevated E2 levels to elicit LH release. Similar changes in blood hormones were not found in LR.

Influence of the oviduct on sperm capacitation in the rabbit.

PIP: In an effort to evaluate the influence of the oviduct on sperm capacitation, in vitro fertilization of freshly-ovulated rabbit ova was used to assay the fertilizing ability of spermatozoa. New Zealand white rabbits were used. 9 1/2 hours after injection of human chorionic gonadotrophin half the animals had fimbriae of both tubes resected; 2 hours later, the ovaries were excised and the ova in cumulus removed from the surface of the ovaries. Half the animals serving as donors of uterine spermatozoa had their oviducts removed; half were intact. Both had spermatozoa recovered from their uteri 6-48 hours after mating. Study technique is detailed. Studies of 617 ova showed best fertilization rates when spermatozoa had remained in the uteri 16-18 hours. Spermatozoa recovered from capacitators without oviducts produced similar cleavage rates as those with intact oviducts. Results indicate that spermatozoa can be capacitated in the uterus of rabbits without oviducts but it is possible that part of the capacitation normally takes place in the oviducts. Others have shown capacitation takes longer by several hours with the uterotubal junction ligated than when this junction is patent. Ova were fertilized by spermatozoa recovered from the uterus after 8 hours but not by those recovered after 6 hours. In the present experiment spermatozoa recovered from the uterus 36 hours postcoitus were still able to fertilize ova.^ieng

Factors in diminution of uteroglobin secretion in the rabbit.

Uteroglobin was measured under various hormonal conditions: pregnancy, pseudopregnancy, pseudopregnancy with exogenous progesterone, pseudopregnancy with exogenous 20alpha-hydroxyprogesterone, ovariectomy with exogenous progesterone, ovariectomy with exogenous estrogen, ovariectomy with exogenous estrogen and progesterone, and ovariectomy with either exogenous progesterone or estrogen and progesterone, plus uterine trauma. In pregnant females, uteroglobin levels diminished sharply after day 9. In pseudopregnancy, high concentrations were maintained through day 14. Although exogenous progesterone did not prevent this decrease in pseudopregnant females, re-elevation occurred in the continued presence of progesterone. A similar pattern of decline and re-elevation was found in ovariectomized females that received injections of estrogen and progesterone. With an increase in estrogen dosage, the period of uteroglobin secretion was shorter and the magnitude lower. Ovariectomized females receiving only progesterone did not manifest a clear uteroglobin diminution. Uterine trauma on day 7 of exogenous steroid administration to ovariectomized females was followed by a diminution in uteroglobin. At the dosage level used, administration of 20alpha-hydroxyprogesterone did not affect the peak uteroglobin secretion occurring on day 5 of pseudopregnancy. Ovariectomized females receiving estrogen or sesame oil vehicle had barely detectable levels of uteroglobin. A uteroglobin-estrogen complex is suggested as a possible inhibitor of uteroglobin synthesis by a feedback inhibition pathway in pseudopregnant females and in ovariectomized females treated with progesterone plus estrogen. In pregnant females, a uteroglobin-estrogen complex and/or the uterine decidual response to implantation could control uteroglobin synthesis.