Pharmacological options in resistent ovary syndrome and premature ovarian failure.

PURPOSE: To present methods of treating women in apparent ovarian failure to allow them to ovulate and conceive. METHODS: Ethinyl estradiol was used to lower elevated serum follicle stimulating hormone (FSH) levels to restore down-regulated FSH receptors on the follicle. Ovulation and pregnancy rates were then determined. Aggressive progesterone (P) therapy in the luteal phase was also used. Lowering elevated serum FSH with gonadotropin releasing hormone agonists was also successful in inducing ovulation in these patients. RESULTS: Several anecdotal studies have demonstrated that ethinyl estradiol therapy can induce ovulation in women in apparent menopause and achieve live births. CONCLUSIONS: The advantage of ethinyl estradiol over other estrogens to induce ovulation in hypergonadotropic women is that it does not cross-react in the assay for serum estradiol and can allow detection of estradiol secretion by the follicle. Thus estrogen therapy is by far the most effective treatment.

Bone mineral density changes on androgen deprivation therapy for prostate cancer and response to antiresorptive therapy.

Androgen deprivation therapy improves survival of patients with prostate cancer and leads to hypogonadal state. Gonadal hormones are essential for skeletal integrity and hypogonadism constitutes a major risk factor for osteoporosis. To examine the bone loss secondary to androgen deprivation therapy, we reviewed the bone mineral density (BMD) studies of 152 patients with prostate cancer with mean duration of androgen deprivation therapy of 58 months. Among them 55 subjects had follow-up BMD measurement at 12-15 months with 39 of them on antiresorptive therapy. Osteoporosis was noted at least at one site in 92 (60.5%), among which 74 (48.7%) had changes at hip with the more prominent changes at ward's triangle, 18 (11.8%) at other sites. Osteopenia was present in 37 (24%) and only 17 (11%) were normal. The duration of antiandrogen therapy did not correlate with the degree of bone loss. Significant in improvement in the BMD is noted at 12-15 month follow-up on antiresorptive therapy. We conclude that men treated with androgen deprivation therapy are at risk for bone loss and should have BMD measured at the time of initiation of androgen deprivation therapy and periodically.

Orbital metastasis as a first indication of prostate cancer: a case report.

Prostatic carcinoma accounts for only 3.6% of orbital metastases encountered in clinical practice. We report the clinical presentation and response to treatment of a patient with metastatic prostatic carcinoma to the sella turcica. A 73-year-old man presented with a three-months history of progressive right proptosis associated with increasing diplopia in down-gaze and slightly decreased visual acuity. Gadolinium-MRI scans of the head revealed a left osteoblastic intrasellar mass, displacing the pituitary gland. Laboratory testing revealed a serum PSA level of 22 ng/ml. Transrectal ultrasound-guided biopsy revealed prostatic adenocarcinoma (Gleason score 4+3) in both lobes of the prostate. A bone scan was performed showing that the patient had multiple secondary bony lesions. Total androgen blockade was initiated. Moreover, he was referred for radiotherapy of this metastatic lesion to the sella turcica. The visual complaints regressed dramatically within the first month of the treatment. A follow-up MRI scan at 6 months showed almost complete involution of the orbital metastatic process. However the disease subsequently progressed and the patient died 22 months after diagnosis.

Increasing use of gonadotropin-releasing hormone agonists for the treatment of localized prostate carcinoma.

BACKGROUND: The role of androgen deprivation therapy in prostate carcinoma is controversial in earlier stages of disease. The authors examined the time trends and patterns of use for androgen deprivation in the form of gonadotropin-releasing hormone (GnRH) agonists or orchiectomy, in population-based tumor registries. METHODS: Data were obtained from the linked Surveillance, Epidemiology and End Results-Medicare database. A total of 100,274 men with prostate carcinoma diagnosed from 1991 through 1999 were selected. The main outcome was the proportion of men who received >/= 1 dose of a GnRH agonist in the first 6 months of diagnosis. This was plotted by year and stratified for age, grade, stage as well as primary versus adjuvant usage. Multiple logistic regression was used to examine predictors of GnRH agonist use in the subset of patients with localized cancer. RESULTS: There was a consistent increase in GnRH agonist use by year for all ages, stages, and grades. Even in men >/= 80 years with localized stage and low to moderate grade tumors, primary GnRH agonist use increased over the study period, from 3.7% in 1991 to 30.9% in 1999 (P < 0.001). The multivariable analysis showed that significant variability in GnRH agonist use existed among SEER geographic regions. CONCLUSIONS: The use of GnRH agonists for prostate carcinoma increased dramatically during the 1990s. This increase occurred across all stages and histologic grades of prostate carcinoma, and was greatest in patients >/= 80 years.

Plasma steroid profiles following follicle-stimulating hormone or equine chorionic gonadotropin injection in cows chronically treated with gonadotropin-releasing hormone agonist.

Plasma steroid profiles following follicle-stimulating hormone (FSH) or equine chorionic gonadotropin (eCG) injection were studied in chronically gonadotropin releasing hormone agonist (GnRH-A)-treated cows. Follicular development and irINH secretion were stimulated by FSH or eCG injection. The plasma concentrations of estradiol-17 beta (E(2)) and testosterone (T) were markedly increased following eCG injection. However, significant increases of the plasma E(2) and T concentrations were not detected in FSH-treated cows. Ovulation of developed follicles were depended on the hCG injection in both groups. These results show: 1) Follicular response to an exogenous gonadotropin is still remained, 2) Ovulation of developed follicles is induced by hCG injection and 3) FSH and eCG cause disparate plasma steroid profiles, under the influence of repeated GnRH-A treatment.

Failure to maintain the suppressed level of serum testosterone during luteinizing hormone-releasing hormone agonist therapy in a patient with prostate cancer.

A 75-year-old man with metastatic prostate cancer had been treated with goserelin acetate, and prostate specific antigen (PSA) had decreased, but 11/2 years after beginning the treatment of goserelin acetate, PSA was markedly elevated and serum testosterone was at normal level. After castration the serum testosterone was at castrate level and PSA decreased. In the present case, leuprorelin acetate 1-month depot suppressed the luteinizing hormone level in 1 month, even after the patient underwent castration.

Fetal growth and reproductive performance in ewes administered GnRH agonist on day 12 post-mating.

Reproductive performance and fetal growth was determined in GnRH (4 microg synthetic GnRH agonist, Receptal) administered (i.m.) to ewes on day 12 post-mating (n = 103) compared to control ewes (n = 97) during the breeding season. Plasma progesterone and LH concentrations were analyzed. A total of 13 ewes was slaughtered on day 45 of pregnancy (six from control, seven from GnRH treated groups). GnRH administration on day 12 post-mating increased plasma progesterone concentration (4.39+/-0.25 ng/ml) compared to control group (3.43+/-0.15 ng/ml) on days 13-15 post-mating (P < 0.01). GnRH administration also increased plasma LH concentration between 1 and 4 h after GnRH administration (P < 0.01). Pregnancy rate was higher in GnRH treated group (84%) than control (66%) group (P < 0.05). The ewes in GnRH administered group had more twins (P < 0.05) than those in control group. The ovarian weights (P < 0.05) and the number of corpora lutea (CL) (P < 0.01) were greater in ewes slaughtered on day 45 of pregnancy in GnRH treated group than those in control group. GnRH administration on day 12 post-mating did not have any effect on products of conception at day 45 of pregnancy except on crown-rump length (CRL) of fetuses and cotyledon weight. CRL of fetuses and cotyledon weight in GnRH treated group was higher than those in control group (P < 0.05). In conclusion GnRH administration improved reproductive performance of ewes when administered on day 12 post-mating probably through its beneficial effect on embryo survival by enhancing luteal function, but not through stimulating fetal growth.

Endometrial preparation for frozen-thawed embryo transfer with or without pretreatment with gonadotropin-releasing hormone agonist.

OBJECTIVE: To test the efficacy of endometrial preparation with exogenous steroids, without pretreatment with gonadotropin-releasing hormone (GnRH) agonist, in women with normal ovarian function. DESIGN: Prospective randomized study. SETTING: Private outpatient infertility clinic. PATIENT(S): Two hundred ninety-six women undergoing frozen-thawed embryo transfer. INTERVENTION(S): In group 1 (146 patients), depot GnRH agonist was administered in the luteal phase; treatment with 17beta-estradiol transdermal patches at steadily increasing dosage from 100 to 300 microg was then given for at least 12 days. In group 2 (150 patients), endometrial preparation began on day 1 of menstrual cycle. The starting dose was 200 microg; this was increased to 300 microg after 7 days. MAIN OUTCOME MEASURE(S): Pregnancy, abortion, implantation and cancellation rates. RESULT(S): In group 2, six cycles (4%) were cancelled due to evidence of ovulation. Groups were similar in the percentage of embryos that survived freezing-thawing (77.1% in group 1 and 76.6% in group 2) and in the number of embryos transferred per patient (2.1 +/- 0.6 and 2.1 +/- 0.7, respectively). Groups 1 and 2 did not differ significantly in rates of pregnancy (19.7% and 24.1%), abortion (17.8% and 11.7%), and implantation (10.4% and 11.9%). CONCLUSION(S): Endometrial preparation for frozen-thawed embryo transfer based exclusively on steroid administration appears to be as effective as the more conventional protocol involving preliminary desensitization with a GnRH agonist. This simplified protocol reduces costs, minimizes pharmacologic treatment, and increases patient compliance.