leuprolide and Hyperplasia

Mitogenesis and mutagenesis are major driving forces in neoplastic development. Little is known about important breast mutagens, but much is known about breast mitogens. "Blocking" the effect of breast cell mitogens, by reducing the actual exposure of the breast to them, is an obvious strategy for breast cancer prevention. The ovarian hormones, estrogens and progesterone, are major effective (direct or indirect) breast cell mitogens. There is overwhelming epidemiologic evidence that breast cancer risk is closely related to exposure to estrogens and progestogens. A woman's exposure to endogenous ovarian estrogens and progesterone is drastically reduced by the use of combination-type oral contraceptives (COCs), but the exogenous synthetic estrogen and progestogen in the COC effectively replace the ovarian estrogen and progesterone, so that no decrease in breast cell exposure to these hormones is obtained. Doses of estrogen and progestogen in modern COCs are close to the minimum attainable, while still retaining both contraceptive efficacy and ovarian suppression (so that endogenous estrogen and progesterone do not add to the dose of estrogen and progestogen from the COC). Considerably lower effective breast cell exposure to estrogen and progestogen can, however, be achieved by using a gonadotropin-releasing hormone agonist to suppress ovarian function and compensating for the resulting hypoestrogenemia with low-dose hormone replacement. Such a contraceptive is predicted to reduce lifetime breast cancer risk by more than 50% if used for 10 years and by as much as 70% following 15 years of use. Contraception represents a unique opportunity to have a substantial beneficial impact on women's health; more than 10 million women use COCs daily in the United States.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Age Factors; Bone Density; Breast Neoplasms; Cardiovascular Diseases; Case-Control Studies; Cell Division; Contraceptives, Oral, Combined; Contraceptives, Oral, Hormonal; Drug Utilization; Endometrial Neoplasms; Endometrium; Estrogen Replacement Therapy; Estrogens; Female; Gonadotropin-Releasing Hormone; Humans; Hyperplasia; Incidence; Leuprolide; Middle Aged; Neoplasms, Hormone-Dependent; Osteoporosis; Ovarian Neoplasms; Pilot Projects; Premenopause; Progesterone; Progestins; Reproductive History; Risk Factors; Testosterone

Hyperandrogenism is a relatively common clinical problem. However, severe hyperandrogenism causing virilisation is rare. A 27-year-old woman presented with generalised hirsutism, clitoromegaly, breast atrophy and secondary amenorrhoea. She had serum testosterone levels elevated to the adult male range. Administration of gonadotropin-releasing hormone (GnRH) analogue resulted in >50% suppression of serum testosterone which was suggestive of luteinising hormone-dependent ovarian hyperandrogenism. Imaging studies of abdomen and pelvis were normal, and ovarian venous sampling failed to show a gradient between the two sides. A presumptive diagnosis of ovarian hyperthecosis was, therefore, considered. Medical treatment with GnRH analogue and combined oral contraceptive pills was initiated to which an excellent clinical and biochemical response was noted. This case highlights a rare presentation of ovarian hyperthecosis in a young woman with severe hyperandrogenism mimicking a virilising neoplasm.

Topics: Adult; Amenorrhea; Contraceptives, Oral; Female; Humans; Hyperandrogenism; Hyperplasia; Leuprolide; Testosterone; Theca Cells; Treatment Outcome

Topics: Adrenal Cortex; Adrenocortical Hyperfunction; Female; Humans; Hydrocortisone; Hyperplasia; Leuprolide; Luteinizing Hormone; Middle Aged; Pituitary ACTH Hypersecretion

Few studies have been performed on the vascular changes in leiomyomas from patients treated with gonadotropin-releasing hormone agonists (GnRHAs).. To measure luminal diameter and wall thickness of arterioles in uterine leiomyomas using a quantitative stereologic method of analysis.. Thirty leiomyomas from 3 study groups were used: (1) patients treated with GnRHAs (10 patient samples), (2) age-matched controls (10 patient samples), and (3) postmenopausal women (10 patient samples). Measurements of arteriolar luminal diameter and wall thickness were made using a video-based, computerized system attached to the microscope, for which a morphometric ad hoc program was written. Electron micrographs were made of random arterioles from the first 2 groups (GnRHA-treated patients and age-matched controls).. Department of Pathology, Mount Sinai School of Medicine, New York, NY.. A total of 30 patient samples were studied, with 3 groups comprising 10 samples each, including patients treated with GnRHAs, age-matched control patients, and postmenopausal women.. Arterioles in myomas from patients treated with GnRHAs had slightly larger luminal diameters and significantly thicker walls than age-matched controls and resembled arterioles from postmenopausal women. The thickening was due to smooth muscle cell hyperplasia in the muscularis media.. Treatment with GnRHAs causes a thickening of the walls of intramyomatous arterioles, which resemble those of postmenopausal women. This thickening may play a role in the decreased flow of blood reported in GnRHA treatment.

Topics: Adult; Arterioles; Female; Humans; Hyperplasia; Leiomyoma; Leuprolide; Microscopy, Electron; Middle Aged; Muscle, Smooth, Vascular; Nafarelin; Postmenopause; Uterine Neoplasms

Hyperthecosis in a postmenopausal woman is a very rare cause of virilization, and only five cases have been reported previously.. A woman presented with a nine-year history of increasing hirsutism and a mild virilization beginning in the perimenopausal period. Initial androgen metabolite concentrations suggested attenuated late-onset adrenal hyperplasia, but a trial of dexamethasone treatment was ineffective. Subsequent use of leuprolide acetate resulted in a biochemical and clinical improvement in the signs and symptoms.. This case is unique because gonadotropin-releasing hormone agonist administration was utilized as both a diagnostic and therapeutic modality.

Topics: Adrenocortical Hyperfunction; Androgens; Delayed-Action Preparations; Drug Therapy, Combination; Estrogens, Conjugated (USP); Fallopian Tubes; Female; Gonadotropin-Releasing Hormone; Gonadotropins; Humans; Hyperplasia; Hysterectomy; Leuprolide; Medroxyprogesterone Acetate; Middle Aged; Ovarian Diseases; Ovariectomy; Ovary; Postmenopause; Progesterone Congeners; Virilism

Androgenic manifestations coexisting with hilus cell hyperplasia adjacent to a tumour or an ovarian cyst are extremely rare. We report the case of a post-menopausal woman with hirsutism associated with hilus cell hyperplasia within the wall of an ovarian cyst. The pattern of steroid secretion revealed increased testosterone release. Suppression of testosterone to 'normal range' was seen in response to leuprolide administration. This new approach demonstrates gonadotrophin dependence of hilus cell hyperplasia within an ovarian cyst.

Topics: Androstenedione; Depression, Chemical; Female; Follicle Stimulating Hormone; Humans; Hyperplasia; Leuprolide; Luteinizing Hormone; Middle Aged; Ovarian Cysts; Ovary; Testosterone