Biomedical subjects

A Moo-Young

Publications and source records attributed to A Moo-Young.

6 recordsLinked to original sources

PubMed2001

Effective long-term androgen suppression in men with prostate cancer using a hydrogel implant with the GnRH agonist histrelin.

OBJECTIVES: To evaluate the effectiveness of a hydrogel implant containing the gonadotropin-releasing hormone (GnRH) agonist histrelin in suppressing testosterone production in men with prostate cancer and to determine the effective dose (one, two, or four implants). METHODS: Forty-two men with prostate cancer and indications for androgen ablation were treated with one, two, or four implants. In two of the clinics, comprising 27 subjects, the treatment period was 12 months, with replacement with the same number of implants at 12-month intervals. In a third clinic, which treated 15 subjects, the implants were left in place for up to 30 months. The total experience was 605 treatment months. RESULTS: The histrelin levels were detected in serum proportional to the number of implants placed. The response, however, was similar among all three dose levels, with testosterone and luteinizing hormone essentially completely suppressed. Serum testosterone levels decreased from 21.9 +/- 17.6 nmol/L to 0.93 +/- 1.57 nmol/L within 1 month and were maintained at 0.55 +/- 0.24 nmol/L at 6 months and 0.60 +/- 0.28 nmol/L after 12 months of treatment. Of the 38 assessable patients, 35 (92%) had castrate levels of testosterone within 4 weeks of the initial implant placement. All patients followed for up for 12 months after placement of the initial set of implants maintained suppression of testosterone production while the implant was in place. CONCLUSIONS: The histrelin hydrogel implant provided adequate and reliable delivery of the potent GnRH agonist histrelin during at least 1 year using a single implant in men with prostate cancer. No apparent advantages were found in using more than one implant, and the question of the possible effectiveness of even lower doses remains open. This treatment modality appears to be both safe and effective.

Aged↗

PubMed1999

Pharmacokinetics of 7 alpha-methyl-19-nortestosterone (MENT) delivery using subdermal implants in healthy men.

We studied the pharmacokinetics of 7 alpha-methyl-19-nortestosterone (MENT), a potent synthetic androgen, administered by subdermal implants. The implants contained 112 +/- 4 mg of MENT acetate in a polyethylene vinyl acetate copolymer. MENT acetate released from the implants is rapidly hydrolyzed to MENT in vivo. Fifteen healthy Finnish men were randomized to have either one, two, or four implants inserted in the medial aspect of the upper arm. The implants remained in place for 4 weeks. Blood samples were obtained before implant insertion, 1, 2, 3, and 4 weeks after insertion, and 1 and 2 weeks after removal. Serum MENT concentrations were determined by gas chromatography with mass selective detection. The MENT levels attained in each implant group remained at a steady level during the 4 weeks of implant use. The mean steady state MENT concentrations in the one, two, and four implant groups were 0.6, 1.4, and 2.3 nmol/L, respectively. Serum MENT concentrations during implant use were clearly dose dependent; the between-subject effect of implants as well as the differences between each pair of groups were all statistically significant. The release rate of MENT from one, two, and four implants was calculated to be approximately 0.3, 0.8, and 1.3 mg/day, respectively. This study suggests that MENT acetate implants are a promising method for long-term androgen administration in hypogonadism and male contraception.

Adult↗

PubMed1999

Correlation of endocrine profiles with bleeding patterns during use of Nestorone contraceptive implants.

The relationship between ovarian hormones and bleeding patterns during continuous progestin contraception was studied in 29 women who used Nestorone (NES) releasing implants. Oestradiol and progesterone were measured in blood samples taken twice a week for 6 consecutive weeks, during months 6, 12, 18 and 24 of implant use. Retrospectively, the association between hormonal concentrations and bleeding patterns was evaluated. Twenty-four short (</= 24 days), 36 normal (25-35 days), 27 long (36-90 days) and nine episodes of amenorrhoea, as well as 28 periods of prolonged bleeding, were identified. Short cycles, periods of prolonged bleeding and amenorrhoea were characterized by low oestradiol concentrations. Bleeding after a normal or long cycle regularly occurred after a rise and fall of oestradiol or oestradiol and progesterone. The duration of bleeding was directly and significantly associated with the highest concentration of oestradiol in the previous 15 days in anovulatory cycles. Luteal activity was associated with shorter duration of bleeding. Periods of prolonged bleeding were usually initiated with a drop in oestradiol and over half ended with an increase in oestradiol. It was concluded that changes in endogenous hormone have a significant influence over the bleeding pattern during use of NES implants.

Adolescent↗

PubMed1999

Parenteral administration of progestin Nestorone to lactating cynomolgus monkeys: an ideal hormonal contraceptive at lactation?

Nestorone (NES) progestin is highly effective for contraception following parenteral administration, but ineffective after oral ingestion due to rapid first-pass metabolism. Thus, NES might be ideal for lactational contraception; possible NES in milk should be metabolized by the nursing infant. We evaluated the distribution of NES, its endocrine effects and infant weight gain in five cynomolgus monkeys and their nursing infants. Nestorone implants, releasing approximately 40 microg NES/day in vitro, were placed s.c. in the mothers 3-4 months following delivery, where they remained in situ for 4 weeks. Sampling (blood daily from the mother; milk and blood from the infant at 3 day intervals) was initiated at 2 weeks prior to insertion, and continued for 2 weeks following removal of the implant. NES, oestradiol, progesterone and prolactin were measured by radioimmunoassays and the infants were weighed weekly. The (mean +/- SD) maternal serum and milk concentrations of NES were 337 +/- 90 and 586 +/- 301 pmol/l during the use of the implants. The ratio of milk/serum NES was 1.68 +/- 0.12 (mean +/- SE), and the serum and milk concentrations were significantly correlated (r = 0. 75, P < 0.001). NES was not detectable (<13 pmol/l) in any infant serum samples. Concentrations of prolactin (mean +/- SD) were 41.1 +/- 32, 26.7 +/- 7.6 and 26.3 +/- 9.5 ng/ml before, during and after the use of the implants respectively. The (mean +/- SE) infant weight increased from 643 +/- 54 g 1 week prior to insertion to 713 +/- 54 g 1 week following removal. These data confirm that NES in milk is rapidly metabolized by the suckling infant. Therefore, NES appears to be an ideal hormonal contraceptive for use during lactation.

Animals↗

PubMed1997

Immunohistochemical localization of testin in the female reproductive system of the rat is consistent with its involvement in the turnover of specialized junctional complexes.

The distribution of testin in the female reproductive system of rats throughout the estrous cycle was examined immunohistochemically. In ovarian follicles, immunostainable testin was localized at the junctions between adjacent granulosa cells. During follicular development, immunostainable testin surrounding the granulosa cells increased in every follicle but was reduced drastically when the follicle was undergoing atresia. Testin was also found in the junctions between adjacent germinal epithelial cells that covered the surface of the ovary, at the lower or the lower lateral borders of each cell. In the uterus and oviduct, immunostainable testin was detected only in the luminal and glandular epithelium, where it formed a polygonal network encircling the apical border of the epithelial cells. During the estrous cycle, there was no drastic change in the distribution of testin in the epithelial cells of the ovary. In the vaginal mucosa, testin was found to be localized only at the junction of the epithelial cells on the surface layer of the stratified epithelium; at different stages of the estrous cycle, distinctive staining for testin could be found at proestrus, metestrus, and diestrus, but not at estrus. It is postulated that testin is a cell junction-associated protein in the female reproductive system.

Animals↗

PubMed1992

Contraception with subdermal implants releasing the progestin ST-1435: a dose-finding study.

A new modified subdermal implant releasing the potent progestin ST-1435 was studied in eleven fertile-aged women. These implants have been developed for contraception and they have a life-time of two years. Three implant lengths of 4, 6 and 8 cm were tested to find the optimal steroid dose for inhibition of ovulation. Serum samples were collected twice per week during a six-week period every six months. The concentrations of serum ST-1435, estradiol and progesterone were determined by RIA. Ovulation was inhibited by all ST-1435 doses tested. The concentration of serum progesterone was below 6 nmol/l in all samples tested showing the absence of luteinization. The concentration of serum ST-1435 increased with increasing ST-1435 dose. Serum estradiol concentrations were quite variable, showing wide range and occasional high peak values typical of progestin treatment; the mean value of serum estradiol concentrations measured did not differ with different ST-1435 doses. The results of steroid determinations led to the conclusion that a single 4 cm subdermal implant is optimal for contraception. With this dosage level, ovulation is inhibited and side effects are minimized. Bleeding control was variable. No hormonal side effects due to the progestin ST-1435 were reported. This method, using a single 4 cm subcutaneous implant releasing the progestin ST-1435 with a life-time of two years, represents a promising alternative for inhibition of ovulation and contraception.

Adult↗