histrelin and Endometriosis

Use of gonadotropin-releasing hormone (GnRH) agonists produces a transient increase and subsequent long-term reduction in concentrations of pituitary hormones, resulting in gonadal hormone suppression. This reversible suppression is useful in treating diseases dependent on these hormones. GnRH agonists have been approved for use in patients with endometriosis, advanced prostate cancer, and precocious puberty. As research continues, GnRH agonists are expected to change the clinical approach to the treatment of many other reproductive and nonreproductive diseases.

Topics: Endometriosis; Female; Gonadotropin-Releasing Hormone; Humans; Male; Prostatic Neoplasms; Puberty, Precocious

To examine possible adverse effects on pituitary function of long-term administration of gonadotropin-releasing hormone agonist (GnRH-a).. Prospective analysis of blood sampling before, during, and after GnRH-a therapy.. Tertiary institutional outpatient care.. Twelve normally ovulatory women with a diagnosis of endometriosis.. Six-month suppression with GnRH-a.. Serum levels of follicle-stimulating hormone, luteinizing hormone, free thyroxin index, cortisol (F), growth hormone (GH), prolactin (PRL), and thyroid-stimulating hormone (TSH).. Basal and stimulated values of gonadotropins, PRL, F, TSH, and GH were normal and unchanged by 6 months of GnRH-a after resumption of menses.. Utilizing dynamic pituitary function tests, we were unable to demonstrate an adverse effect of long-term GnRH-a therapy on pituitary function.

Topics: Adult; Endometriosis; Female; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Growth Hormone; Humans; Hydrocortisone; Luteinizing Hormone; Pituitary Gland; Prolactin; Prospective Studies; Thyrotropin; Thyrotropin-Releasing Hormone; Thyroxine

A limited number of small studies have assessed the efficacy of gonadotropin-releasing hormone agonists in the treatment of ovarian endometriomas. Most of these trials have not used quantitative measurements to evaluate the effects of therapy on disease resolution. The results available thus far suggest that nafarelin, buserelin, and histrelin offer modest degrees of efficacy, similar to that of danazol, in the management of patients with ovarian endometriotic cysts. Gonadotropin-releasing hormone agonists appear to be most efficacious when endometriomas are less than 1 cm in size.

Topics: Buserelin; Danazol; Endometriosis; Female; Gonadotropin-Releasing Hormone; Humans; Nafarelin

Highly potent agonists of gonadotropin-releasing hormone (GnRH) have been shown to reduce pelvic pain due to endometriosis and the size and number of implants seen at laparoscopy. The accompanying symptoms and problems associated with the hypoestrogenism induced by the agonist have reduced its acceptability and raised questions about its safety. In an attempt to optimize this form of therapy, we treated eight women with endometriosis with daily subcutaneous injections of a potent agonist of GnRH plus a daily oral dose of 20-30 mg of medroxyprogesterone acetate for 24 weeks. Ovarian estrogen secretion was reduced to levels seen in castrated women throughout the course of treatment. Markers of hypoestrogenism, such as hot flashes and loss of calcium from bone, were diminished with this regimen compared with previous findings with GnRH agonist alone. Blinded evaluation of laparoscopic photographs failed to reveal improvement or suppression of active endometriosis. The results of this pilot study indicate that the addition of medroxyprogesterone acetate decreases the hypoestrogenic effects of GnRH agonist alone but fails to affect pain or endometriotic implants.

Topics: Adult; Drug Therapy, Combination; Endometriosis; Estradiol; Estrone; Female; Flushing; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Humans; Luteinizing Hormone; Medroxyprogesterone; Medroxyprogesterone Acetate; Pain; Pelvic Neoplasms

Sixteen women with endometriosis were treated with daily subcutaneous injections of a potent agonist of gonadotropin-releasing hormone (GnRH) for six months. Ovarian estrogen secretion was reduced to castrate levels during most of the course of treatment. Blinded evaluation of laparoscopic photographs confirmed marked suppression of visually apparent disease, but biopsy specimens showed occult, inactive endometriosis in most cases. Marked pain relief was noted by all patients. As a result of this "medical oophorectomy," the women experienced severe hot flashes, and many had insomnia and emotional disturbances. Vaginal cytology showed menopausal changes but related symptoms were generally mild. Calcium excretion rose to menopausal levels. High-density lipoprotein and total cholesterol remained unchanged. These results indicate that GnRH agonist administration has impressive effects on endometriotic implants, and these actions may be enhanced with longer therapy. Further development of this new form of therapy should involve either use of lesser degrees of ovarian suppression or adjunctive therapy to counter the side effects of "medical oophorectomy."

Topics: Adult; Cholesterol, HDL; Endometriosis; Estrogens; Female; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Humans; Laparoscopy; Luteinizing Hormone; Ovarian Neoplasms; Ovariectomy; Ovary

Previously, we reported that short term administration of a highly potent GnRH agonist (GnRHa) for 1 month to patients with polycystic ovarian disease (PCO) resulted in complete suppression of ovarian steroidogenesis without measurable effects on adrenal steroid production. This new study was designed to evaluate the effects of long term GnRHa administration in PCO patients with respect to their hormone secretion patterns and clinical responses. Eight PCO patients and 10 ovulatory women with endometriosis were treated daily with sc injections of [D-His6-(imBzl]),Pro9-NEt]GnRH (GnRHa; 100 micrograms) for 6 months. Their results were compared to hormone values in 8 women who had undergone bilateral oophorectomies. In response to GnRHa, PCO and ovulatory women had rises of serum LH at 1 month, after which it gradually declined to baseline. In both groups FSH secretion was suppressed throughout treatment. Serum estradiol, estrone, progesterone, 17-hydroxyprogesterone, androstenedione, and testosterone levels markedly decreased to values found in oophorectomized women by 1 month and remained low thereafter. In contrast, serum pregnenolone and 17-hydroxypregnenolone were partially suppressed, and dehydroepiandrosterone, dehydroepiandrosterone sulfate, and cortisol levels did not change. Clinically, hyperplastic endometrial histology in three PCO patients reverted to an inactive pattern, and proliferative endometrium in two other PCO patients became inactive in one and did not change in the other. Regression of proliferative endometrial histology occurred in all ovulatory women. Vaginal bleeding occurred in all women studied during the first month of GnRHa administration, after which all but one PCO patient became amenorrheic. Hot flashes were noted by all ovulatory women and by four of eight PCO patients. All PCO patients noted subjective reduction of skin oiliness, and five had decreased hair growth. We conclude that in premenopausal women: 1) chronic GnRHa administration results in apparently complete persistent suppression of ovarian steroid secretion; 2) adrenal steroid secretion is not influenced directly or indirectly; and 3) its use may be helpful in the treatment of endometrial hyperplasia and ovarian androgen excess in women with PCO.

Topics: Androgens; Endometriosis; Estrogens; Female; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Humans; Luteinizing Hormone; Ovary; Polycystic Ovary Syndrome; Progestins; Time Factors

The present study was conducted to induce endometriosis in an experimental animal model in which the condition and its response to pharmacologic agents could be quantified. Endometriosis was induced in New Zealand White rabbits by transplanting endometrial sections into various sites throughout the peritoneum. After 7 weeks, the mean implant weight increased in concomitant controls from 10.3 to 89.0 mg. In the next 8 weeks, endometrial implant weight increased to 163.6 mg. Daily subcutaneous administration of a luteinizing hormone-releasing hormone agonist, histrelin, or oral administration of danazol, reduced the ectopic implant weight within 8 weeks to 21.7 and 46.0 mg, respectively. In a group of animals that were bilaterally ovariectomized, implant weight decreased significantly in the same 8-week period to 22.4 mg. Furthermore, histologic analysis of the endometriomas showed that ovariectomy, histrelin, or danazol treatment reduced the number of endometrial glands and atrophied the stroma. We conclude that this animal model represents an excellent method for quantitative evaluation of potential therapeutic agents for endometriosis.

Topics: Animals; Castration; Danazol; Disease Models, Animal; Endometriosis; Female; Gonadotropin-Releasing Hormone; Humans; Luteinizing Hormone; Neoplasm Transplantation; Neoplasms, Experimental; Rabbits; Uterine Neoplasms; Uterus