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Biomedical subjects

R S Schenken

Publications and source records attributed to R S Schenken.

At least 73 records · Page 4Linked to original sources
PubMed1990

Premature luteinizing hormone surges in menopausal gonadotropin-stimulated cycles in monkeys: lack of initiation by progesterone.

The occurrence of spontaneous luteinizing hormone (LH) surges in women receiving human menopausal gonadotropins (hMG) for in vitro fertilization-embryo transfer is a significant clinical problem. One hypothetical mechanism is that premature progesterone (P) secretion occurring in the high estradiol (E2) milieu produced by hMG triggers the spontaneous LH surge. To investigate this possibility, 11 rhesus and cynomolgus monkeys were stimulated with hMG. At maximal ovarian stimulation, monkeys were injected with 15 micrograms/kg P (n = 3), 30 micrograms/kg P (n = 3), or 1,000 IU human chorionic gonadotropin (hCG) (n = 5; controls). Blood for E2, P, and LH was drawn twice daily in the periovulatory period and daily before and after this period. Laparoscopy was performed after P or hCG injection. In the 6 monkeys receiving P, no LH surges were detected. Further, postinjection P profiles and laparoscopy showed no evidence of ovulation. Controls demonstrated laparoscopic and hormonal evidence of ovulation. These findings suggest that P does not trigger LH surges in hMG-stimulated cycles.

Animals↗
PubMed1990

Effects of tamoxifen on corpus luteum function and luteal phase length in cynomolgus monkeys.

Previous data in nonhuman primates have demonstrated that tamoxifen prolongs the luteal phase without altering reproductive hormone levels. A small study in humans found no effect on menstrual cycle length, but an increase in luteal ovarian steroid levels. In view of these conflicting results, we studied the effect of tamoxifen on corpus luteum (CL) function in monkeys (n = 20). Blood was obtained daily beginning cycle day 8, and sera assayed for estradiol (E2), progesterone (P), luteinizing hormone, and follicle-stimulating hormone. Four days after the midcycle E2 peak, laparoscopy confirmed CL formation, and the animals were administered (1) lactose (n = 7), (2) tamoxifen, 0.5 mg.kg-1.d-1 (n = 6), or (3) tamoxifen, 3.0 mg.kg-1.d-1 (n = 7) for 12 consecutive days. Serum collection continued until cycle day 50 or menses, whichever came first. Results indicate a biphasic response among tamoxifen-treated animals, with 7 of 13 developing prolonged luteal phases. There was, however, no significant difference in luteal phase length among the three groups, although when the two groups given tamoxifen were combined, the difference in luteal phase length versus controls approached significance. No differences were found among peak P levels, mean luteal phase P levels, or mean luteal phase gonadotropin levels. No variables were found to correlate significantly with luteal phase length. These results suggest that luteal phase administration of the antiestrogen tamoxifen does not alter pituitary gonadotropin secretion or CL function. However, tamoxifen does prolong luteal phase length in a subset of monkeys, perhaps via a direct effect on the endometrium.

Animals↗
PubMed1990

Effect of 20 alpha-dihydroxyprogesterone on the estrogen-induced bioactive luteinizing hormone surge in ovariectomized monkeys.

Progestins facilitate estrogen induction of the preovulatory luteinizing hormone (LH) surge. A biologically weaker progestin, 20 alpha-dihydroxyprogesterone, is reportedly increased at midcycle, but the importance of 20 alpha-dihydroxyprogesterone in regulating LH release has not been systematically studied. We therefore evaluated the effect of 2 doses of 20 alpha-dihydroxyprogesterone on the bioactive LH surge onset in ovariectomized monkeys. Chronically cannulated monkeys (n = 10) received estradiol (E2) benzoate (50 micrograms/kg) with and without subsequent 20 alpha-dihydroxyprogesterone injections (50 micrograms/kg, n = 3 and 100 micrograms/kg, n = 3). Blood was collected every 15 minutes over preselected intervals and the plasma assayed for bioactive LH and gonadal steroids. Low-dose 20 alpha-dihydroxyprogesterone administration resulted in periovulatory peripheral 20 alpha-dihydroxyprogesterone levels and did not advance the bioactive LH surge onset. In contrast, high-dose 20 alpha-dihydroxyprogesterone resulted in supraphysiological 20 alpha-dihydroxyprogesterone levels, slight increases in progesterone levels, and significant advancement of the surge over E2 benzoate treatment alone. We conclude that periovulatory levels of 20 alpha-dihydroxyprogesterone do not play a role in modulating the estrogen-induced bioactive LH surge.

Animals↗
PubMed1990

Azidothymidine (zidovudine) transport by the human placenta.

The diagnosis of Acquired Immunodeficiency Syndrome (AIDS) is increasingly made in pregnant women, and the disease may be transmitted to the fetus. Azidothymidine (AZT, Zidovudine) is the one therapeutic agent of some promise in this condition. As there is no information on the transport of this drug by the human placenta, such studies were carried out using the single cotyledon placental perfusion system and human placental vesicles. AZT crossed the placenta readily and bidirectionally. The transfer rate was about 70% that of a freely diffusible reference marker, antipyrine, and was comparable in both directions. There was no evidence of active or carrier-mediated transport and no glucuronidated metabolites of the drug were identified in either maternal or fetal compartments. The authors believe that the drug crosses the placenta by diffusion, consistent with its lipophilicity and transport into various blood cells.

Antipyrine↗
PubMed1990

Cocaine disrupts estrous cyclicity and alters the reproductive neuroendocrine axis in the rat.

Although a common drug of abuse, cocaine's effects on cyclic reproductive functions and the neuroendocrine systems regulating these functions have not been studied. Here, we report the effects of cocaine on (1) estrous cyclicity and ovulation rates and (2) the stimulated in vitro release of hypothalamic GnRH and aminergic neurotransmitters directly involved in regulating or modulating GnRH release. Within 7 days of treatment with 10 mg kg-1 day-1 of cocaine HCl subcutaneously, rats demonstrated significant estrous cycle irregularity including repetitive days of estrus and prolonged periods of diestrus. After 6 weeks of treatment, cocaine-treated rats exhibited a 44.3% decrease in ovulation rates. For the in vitro studies, bilaterally ovariectomized rats were injected with cocaine (10 mg kg-1 day-1) or with saline for 2 weeks. Each rat received estradiol benzoate (50 mg kg-1 day-1 s.c.) for 2 days before sacrifice. Hypothalamic slices were prepared, placed in 0.1 ml microchambers and perfused with modified Krebs buffer (pH 7.4) using a programmable perfusion system. Basal release of norepinephrine (NE) and serotonin (5HT) was significantly increased in the cocaine-treated group versus controls. Ten-minute pulses of 10(-7)M progesterone (P4) increase NE and 5HT, but not dopamine (DA), release in the saline-treated group. In contrast, pulses of P4 increased NE, but not 5HT or DA, in the cocaine-treated rats. Ten-minute pulses of 0.1 microM NE increased GnRH release in both saline- and cocaine-treated rats. However, the response to pulsed NE was significantly attenuated in the cocaine-treated group.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Hysterosalpingography in the preoperative evaluation of tubal anastomosis candidates.

The value of the hysterosalpingogram (HSG) in the investigation of women requesting reversal of tubal sterilization has never been established. Accordingly, we reviewed the preoperative HSGs performed on 54 women and the surgical findings of these and 27 additional patients who underwent laparoscopy and/or laparotomy for tubal anastomosis. The observation of interstitial, isthmic, and ampullary obstruction by HSG correctly correlated with surgical findings in 12%, 94%, and 69% of cases, respectively. The decision to perform an anastomosis was made in 14 of 17 (82.4%) tubes with interstitial obstruction, 45 of 51 (88.2%) tubes with isthmic occlusion, and 26 of 36 (72.2%) tubes with ampullary occlusion. When distal tubal occlusion was demonstrated by HSG (36/104 tubes, 34.6%), 10 had no repairable ampullary segments. The site of tubal occlusion on HSG was not predictive of a repairable tube. We conclude that the routine HSG is not warranted in the preoperative evaluation of candidates for tubal anastomosis.

Anastomosis, Surgical↗
PubMed1989

Gamete intrafallopian transfer vs superovulation with intrauterine insemination for the treatment of infertility.

Superovulation with intrauterine insemination (SO-IUI) has been suggested as an alternative to gamete intrafallopian transfer (GIFT), despite the absence of controlled or comparative trials. We retrospectively analyzed all GIFT and SO-IUI cycles performed concurrently from January 1985 to August of 1987 at a single university center. Pregnancy rates were significantly better for GIFT than SO-IUI (P less than 0.001), with an odds ratio of 3.25 (P = 0.001). Stepwise multiple logistic regression identified factors that correlate with pregnancy: absence of endometriosis (P = 0.05), infertility less than 3 years' duration (P = 0.002), TMS greater than or equal to 30 X 10(6) (P = 0.005), and treatment with GIFT rather than SO-IUI (P = 0.001). These data give a first approximation of the increased efficacy of GIFT versus SO-IUI and provide valuable insight into significant confounding variables to be considered when planning a randomized, prospective trial to evaluate these techniques.

Adult↗
PubMed1989

Effect of ovarian endometriosis on ovulation in rabbits.

To study the relationship between endometriosis and ovulatory dysfunction, we induced ovarian endometriosis in the rabbit model Adipose tissue was placed in the contralateral ovary as a control. Ovulation was induced with human chorionic gonadotropin, and ovulation points were counted before and after induction of endometriosis. Periovarian adhesions were graded, and ovaries were histologically examined. A significant decrease in the number of ovulation points was observed in ovaries with endometrial tissue (p = 0.001) but not in ovaries that contained adipose tissue (p = 0.095). Periovarian adhesions decreased the number of ovulation points (p less than 0.01) in ovaries that contained adipose or endometrial tissues. Multivariate analysis demonstrated that an increase in adhesion severity was correlated with a decrease in the number of ovulation points (p less than 0.05), but endometrial tissue was not (p = 0.45). We conclude that, in the rabbit model, minimal ovarian endometriosis impairs ovulation primarily through a mechanism related to periovarian adhesions.

Analysis of Variance↗
PubMed1989

Gonadotropin-releasing hormone antagonists attenuate estrogen/progesterone-induced hyperprolactinemia in monkeys.

Previous studies have documented that exogenous gonadotropin-releasing hormone (GnRH) stimulates prolactin (PRL) secretion and augments thyrotropin-releasing hormone-induced PRL release. Further, the concomitant pulsatile release of PRL and luteinizing hormone (LH) suggests that GnRH may be an important regulator of PRL release in certain physiologic states. The authors explored this possibility by evaluating the effect of a GnRH antagonist ([Ac-pClPhe1, pClPhe2, DTrp3, DAla10]-GnRH; GnRH-antagonist) on PRL secretion in monkeys with induced hyperprolactinemia. Monkeys were given estradiol (E2) benzoate 25 mg/kg intramuscularly (IM) on cycle days 1 to 28, and a 3-cm progesterone (P) silastic capsule was placed on cycle day 15 and removed on day 28. On cycle days 15 to 28, monkeys were given IM injections of 1 mg/kg GnRH-antagonist (n = 3), 2 mg/kg GnRH-antagonist (n = 3), or vehicle (n = 3). Daily blood samples were assayed for E2, P, and PRL. The degree of PRL elevation was calculated as percent increase in area under the curve for days 15 to 28 when compared with days 1 through 14 (baseline). Luteinizing hormone levels were calculated similarly. Results indicate a dose-dependent effect of GnRH-antagonist on PRL secretion, with the larger dose producing a significantly lower hyperprolactinemic response, as well as a decline in LH. Thus, GnRH-antagonist attenuates induced hyperprolactinemia in a dose similar to that which suppresses LH release. These findings suggest that GnRH is a physiologic regulator of pituitary PRL secretion. In addition, GnRH analogs may be of benefit in controlled ovarian hyperstimulation by attenuating gonadotropin-induced hyperprolactinemia, thereby reducing potential adverse effects on fertility.

Animals↗
PubMed1989

Laser-induced fluorescence of ectopic endometrium in rabbits.

Endometriosis appears under a wide array of morphologies, and early microscopic disease escapes visual inspection. To improve endoscopic diagnosis, we studied the optical properties of ectopic endometrial tissue, in particular laser-induced fluorescence. Photosensitive drugs were used to obtain a selective signal. Five groups of four rabbits underwent surgical induction of endometriosis and were treated with estrogens for 5 weeks to stimulate growth of the implants. Intramuscular injections of vehicle, tetracycline hydrochloride, 6-demethyl-6-deoxytetracycline hydrochloride, tamoxifen citrate, and clomiphene citrate were given 24 hours before exposure of the tissues to argon-ion laser (351.1 nm + 363.8 nm; power density approximately 1.5 mW/cm2). Fluorescence was documented on photographic film. In controls, peritoneum and ovaries showed a dim, white-yellow fluorescence, whereas other tissues exhibited blue tones. Animals treated with tetracycline hydrochloride or tamoxifen citrate showed yellow fluorescence of active endometrial implants and the uterotomy site. Two implants, histologically without viable glandular tissue, did not fluoresce. Treatment with 6-demethyl-6-deoxytetracycline hydrochloride yielded signals of lower intensity. Clomiphene citrate caused fluorescence of the uterotomy site only. This experiment demonstrates that, of the compounds used, tamoxifen is the best selective photoenhancer for endometriotic implants and clomiphene is best for the uterotomy site. This study establishes the potential of these drugs for photoradiation diagnosis and possible treatment of diseases involving ectopic endometrium.

Animals↗
PubMed1987

Effect of pregnancy on surgically induced endometriosis in cynomolgus monkeys.

There are few objective data to support the clinical impression that pregnancy exerts a beneficial effect on endometriosis. In this study, we examined the progression-regression of endometriosis in pregnant and nonpregnant monkeys. Endometriosis was surgically induced in 16 monkeys and classified as minimal (n = 5), mild (n = 5), moderate (n = 4), or severe (n = 2). Monkeys were mated and pregnancy occurred in three monkeys with minimal, three with mild, and one with moderate endometriosis. Laparotomy was performed to stage the disease and to obtain biopsy specimens of implants 1 month post partum or 6 to 8 months after initial operation in nonpregnant monkeys. Monkeys with minimal and mild disease had complete regression of macroscopic disease. Histologic examination of the implants showed only fibrosis and hemosiderin deposits, except in one animal with mild endometriosis containing microscopic foci of endometrial glands. The one monkey with moderate disease had significant, but not complete regression of implants. Endometriosis in nonpregnant monkeys tended to progress. These findings demonstrate that pregnancy does exert a beneficial effect on endometriosis and suggest that pregnancy commonly results in complete resolution of minimal or mild disease.

Animals↗
PubMed1986

Histologic and hormonal documentation of the luteinized unruptured follicle syndrome.

Histologic and hormonal documentation of a luteinized unruptured follicle that occurred during a spontaneous menstrual cycle in a rhesus monkey is presented. Frequent (every 2 hours) blood sampling to assess midcycle hormonal dynamics in the monkey with the luteinized unruptured follicle and in five monkeys with an ovulatory stigma revealed significant aberrations in the gonadotropin and steroid hormone profiles associated with a luteinized unruptured follicle. Although the midcycle 17 beta-estradiol surge was normal, the monkey with the luteinized unruptured follicle demonstrated (1) blunted midcycle bioassayable luteinizing hormone, immunoassayable luteinizing hormone, and follicle-stimulating hormone surges; (2) absence of disparity in the bioassayable luteinizing hormone: immunoassayable luteinizing hormone ratio during the gonadotropin surge; (3) absence of progesterone and 17 alpha-hydroxyprogesterone secretion during the gonadotropin surge; and (4) delayed and blunted rise in progesterone and 17 alpha-hydroxyprogesterone after the gonadotropin surge. These findings suggest that an impaired luteinizing hormone surge, perhaps mediated by insufficient midcycle progestin secretion, is one possible cause of the luteinized unruptured follicle syndrome.

17-alpha-Hydroxyprogesterone↗
PubMed1986

Follicle-stimulating hormone blocks estrogen-positive feedback during the early follicular phase in monkeys.

Normally cycling rhesus monkeys were treated with 12.5 IU of follicle-stimulating hormone (FSH; n = 9) or saline (n = 9) on cycle days 1 to 4, 1 to 6, or 1 to 8 and 50 micrograms/kg estradiol benzoate (E2B, intramuscularly) on day 1, 3, or 5, respectively. Blood was collected daily, then every 8 hours for 96 hours after E2B treatment. Serum was assayed for FSH and luteinizing hormone (LH) by radioimmunoassay. Laparoscopy and serum E2 levels were used to assess ovarian follicular development. Eight of nine FSH-treated monkeys failed to demonstrate typical LH surges in response to E2B. One monkey treated with E2B on day 1 had an attenuated LH surge. All nine control monkeys demonstrated typical threefold LH increases within 72 hours after E2B treatment. Supraphysiologic ovarian stimulation was not visibly evident until 5 days after initiation of FSH treatment. These results suggest that the FSH-induced blockade of estrogen-positive feedback for the LH surge antecedes overt ovarian hyperstimulation.

Animals↗