leuprolide and Genital-Diseases--Female

Thanks to recent advances in biotechnology, the use of peptides and proteins as drugs has become a concrete clinical reality, and consequently an interesting challenge has emerged for non-parenteral drug delivery. Leuprolide is a synthetic nonapeptide agonist to the luteinizing hormone-releasing hormone (LH-RH) receptor with principal clinical applications for prostate cancer. Although a large number of formulations available, they mainly consist in depot subcutaneous injections or implantable devices. Both of these routes of administration present multiple limitations considering the large clinical applications of this active substance.. The objective of this review is to critically discuss the formulations currently available on the market for leuprolide optimization and to consider how drug delivery plays an important role in improving the bioavailability of this compound.. Due to its physicochemical properties and its economical market, leuprolide is an interesting candidate for drug delivery to improve the efficacy of existing treatments, dose adjustments, and patient compliance and safety.

Topics: Administration, Cutaneous; Administration, Intranasal; Administration, Oral; Administration, Sublingual; Amino Acid Sequence; Antineoplastic Agents, Hormonal; Breast Neoplasms; Chemistry, Pharmaceutical; Endometriosis; Female; Genital Diseases, Female; Gonadotropin-Releasing Hormone; Humans; Infusions, Parenteral; Injections, Subcutaneous; Leuprolide; Male; Prostatic Neoplasms; Puberty, Precocious; Receptors, LHRH

The aim of this study is to evaluate the association between GnRH analogues and ipriflavone, drug modulating the bone turnover limiting the negative bone effects of analogue. Thirty patients (33 +/- 5.4 years, mean +/- SD) affect by benign gynecological conditions in which there was an indication to use GnRH analogs have been treated with leuprolide acetate at the monthly intramuscular dose of 3.75 mg, for six months. Fifteen of these patients also received 600 mg/day per os of ipriflavone (group A), while the other 15 patients have been treated exclusively with leuprolide acetate (group B). Before and after treatment, radial bone mineral density (BMD) and main markers of bone turnover were measured in all patients. Before treatment no difference in the considered parameters could be detected between the two groups. In group A, after 6 months of treatment no significant decrease in BMD and no variations in the bone turnover parameters. On the contrary, in group B, after six months of treatment, a significant decrease (p < 0.05) in BMD was observed in comparison to basal and group A values. In the same group alkaline phosphatase, osteocalcin and urinary calcium/creatinine and hydroxyproline/creatinine ratio proved significantly increased in comparison to basal and group A values (both with p < 0.05). Ipriflavone, therefore, seems to be effective in counteracting the negative effects of GnRH-a induced on bone.

Topics: Analgesics; Antineoplastic Agents, Hormonal; Bone Remodeling; Female; Genital Diseases, Female; Genital Neoplasms, Female; Humans; Isoflavones; Leuprolide; Osteoporosis; Time Factors

To assess the effects of a hypoestrogenic state on adhesion formation and reformation and on wound healing in the rat model.. Prospective, randomized study (Canadian Task Force classification I).. Forty-eight female Sprague-Dawley rats.. Rats were injected with gonadotropin-hormone releasing hormone (GnRH) agonist and control rats with normal saline. Two weeks later (day zero) laparotomy was performed to create adhesions and a full-thickness wound on the flank. On day 14 the adhesions were scored and liberated. The rats were sacrificed on day 28 and adhesion reformation was evaluated. The wound surface area was measured serially until complete closure.. Mean adhesion scores on day 14 after adhesion formation were not significantly different between GnRH agonist and control groups. Preadhesiolysis and postadhesiolysis scores were not significantly different. There was no significant difference in size of wounds between groups on days zero, 7, or 14.. Administration of a GnRH agonist does not seem to influence postoperative adhesion formation or wound healing in the rat model. (J Am Assoc Gynecol Laparosc 8(1):124-128, 2001)

Topics: Animals; Female; Fertility Agents, Female; Genital Diseases, Female; Gynecologic Surgical Procedures; Leuprolide; Postoperative Period; Rats; Rats, Sprague-Dawley; Tissue Adhesions; Wound Healing

Topics: Female; Genital Diseases, Female; Gonadotropin-Releasing Hormone; Humans; Leuprolide

The chemical structure of luteinizing-hormone-releasing hormone (LHRH) was discovered in 1971 after more than a decade of intensive effort. Subsequent physiologic studies in primates and humans showed that the biologic activity of LHRH depends on the way in which the hormone is administered. Pulsatile administration of LHRH, which mimics the natural secretory pattern, causes sustained secretion of the gonadotrophins. This method of administration has been used to induce ovulation in women with hypothalamic amenorrhea and to induce puberty and spermatogenesis in men with hypogonadotrophic hypogonadism. Continuous infusion, however, produces only transient stimulation of gonadotrophin secretion, followed by a "desensitization" response in which gonadotrophin secretion is inhibited. Thus, LHRH can either augment or inhibit gonadotrophin secretion depending on the mode of administration. Recently, long-acting synthetic analogs of LHRH have been shown to desensitize the pituitary gland and inhibit gonadotrophin release when administered as a single daily subcutaneous injection. These LHRH analogs have proved highly effective in the treatment of prostatic carcinoma and central precocious puberty. They are also being studied as a new approach to contraception and to the treatment of endometriosis and polycystic ovary syndrome.

Topics: Animals; Child; Contraceptive Agents, Male; Endometriosis; Estrogens; Female; Follicle Stimulating Hormone; Genital Diseases, Female; Genital Diseases, Male; Gonadotropin-Releasing Hormone; Humans; Hypogonadism; Hypothalamic Diseases; Infertility; Leuprolide; Luteinizing Hormone; Male; Neoplasms, Hormone-Dependent; Ovulation Induction; Polycystic Ovary Syndrome; Prostatic Neoplasms; Puberty, Precocious; Spermatogenesis; Time Factors; Triptorelin Pamoate