RESUMEN
The effects of norgestimate triphasic (Ortho Tri-Cyclen, Tri-Ciles) and levonorgestrel triphasic (Triphasi) formulations on lipid and androgen metabolism were assessed in a study of 66 healthy women treated through six menstrual cycles. Levels of the following were measured: cholesterol and its subfractions, triglycerides, carrier lipoproteins, estradiol, testosterone, and sex hormone binding globulin (SHBG). Comparison of baseline values with values after 3 and 6 months of treatment indicated that both regimens influenced lipid and androgen metabolism. There was a statistically significant between-regimen difference in levels of high-density lipoprotein, which were favorably increased with norgestimate triphasic but reduced with levonorgestrel triphasic. Related data on SHBG showed that plasma levels of this marker of estrogen/androgen balance were increased significantly more in the norgestimate triphasic group, providing additional evidence of low androgenicity. Both regimens inhibited follicular growth to the same extent, as evidenced by low mean levels of estradiol in all on-therapy cycles; and both decreased free testosterone. Side effects in both groups were minor and characteristic of those observed with low-dose oral contraceptive agents. The results of the study support the reported safety and positive effects of norgestimate on lipid and androgen metabolism, in comparison with a levonorgestrel-containing combined oral contraceptive.
PIP: The effects of norgestimate triphasic (Ortho Tri-Cyclen, Tri-Cilest) and levonorgestrel triphasic (Triphasil) formulations on lipid and androgen metabolism were assessed in a study of 66 healthy women who were treated through 6 menstrual cycles. Levels of the following were measured: cholesterol and its subfractions, triglycerides, carrier lipoproteins, estradiol, testosterone, and sex hormone binding globulin (SHBG). Comparison of baseline values after 3 and 6 months of treatment indicated that both regimens influenced lipid and androgen metabolism. There was a statistically significant between-regimen difference in the levels of high-density lipoprotein, which increased favorably with norgestimate triphasic but were reduced with levonorgestrel triphasic. Related data on SHBG showed that plasma levels of this marker of estrogen/androgen balance were increased significantly more in the norgestimate triphasic group, providing additional evidence of low androgenicity. Both regimens inhibited follicular growth to the same extent, as seen by low mean levels of estradiol in all of the on-therapy cycles. Both decreased free testosterone. Side effects in both groups were minor and characteristic of those observed with low-dose oral contraceptives (OCs). The results of the study support the reported safety and positive effects of norgestimate on lipid and androgen metabolism, in comparison with a levonorgestrel-containing combined OC.
Asunto(s)
Andrógenos/sangre , Anticonceptivos Orales Combinados/farmacología , Levonorgestrel/farmacología , Lípidos/sangre , Norgestrel/análogos & derivados , Adolescente , Adulto , Presión Sanguínea/efectos de los fármacos , Peso Corporal/efectos de los fármacos , Anticonceptivos Orales Combinados/efectos adversos , Femenino , Humanos , Levonorgestrel/efectos adversos , Norgestrel/efectos adversos , Norgestrel/farmacologíaRESUMEN
The ability of germ cells (spermatocytes and spermatids) and spermatozoa present in human ejaculate to metabolize steroids was studied in men with obstructive infertility who had undergone vasoepididymostomy as corrective surgery. Steroid metabolism by spermatozoa in men who had undergone vasovasostomy was also investigated. Germ cells converted testosterone mainly to androstenedione. In addition to androstenedione, dihydrotestosterone and androstanediols were also formed in incubations using spermatids. Both types of germ cells converted estradiol to estrone. Spermatozoa from subjects who had undergone vasoepididymostomy or vasovasostomy converted testosterone to androstenedione as in normal men, while spermatozoa from infertile subjects converted testosterone mainly to dihydrotestosterone. Seminal fluid, free of germ cells, did not show steroid-metabolizing capability.
PIP: Metabolism of testosterone and estradiol by primary spermatocytes, spermatids and spermatozoa of 6 fertile men, 6 men infertile due to immobile sperm, 8 men who had vasovasostomy, and 11 men who had vasoepididymostomy because of obstruction, was studies by thin layer chromatography. Germ cells were collected at 3-month intervals after surgery, and separated by Percoll gradients. Results were reported as percentages of total counts in substrates and products. Germ cells of normal and post-operative subjects converted testosterone primarily to androstenedione, and their spermatids also formed dihydrotestosterone and androstanediols. Spermatozoa and spermatids also formed estrone from estradiol. Spermatozoa from infertile men primarily produced dihydrotestosterone from testosterone.
Asunto(s)
Epidídimo/cirugía , Células Germinativas/metabolismo , Infertilidad Masculina/cirugía , Espermatozoides/metabolismo , Esteroides/metabolismo , Conducto Deferente/cirugía , Adulto , Anastomosis Quirúrgica , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Mifepristone (RU 486) is a compound with progesterone as well as cortisol-blocking activities. We investigated the endocrine effects of long-term therapy of 10 patients with meningiomas with 200 mg mifepristone daily for 1 yr. Most patients initially complained of nausea, vomiting, and/or tiredness. In four patients prednisone (7.5 mg/day) had to be given simultaneously in order to overcome these side-effects. In retrospect those patients who presented with the most severe side-effects showed the most rapidly occurring activation of the hypothalamo-pituitary-adrenal-axis, as measured by an increase of circulating cortisol levels as well as of urinary cortisol excretion. Therapy with RU 486 activated the hypothalamo-pituitary-adrenal axis, resulting in a resetting of this system at a higher level at which the diurnal rhythm and the responsiveness to CRH stimulation were maintained, whereas the sensitivity to dexamethasone had diminished. Secondarily the production of androstenedione and estradiol increased considerably. These endocrine changes were caused by the induction of partial cortisol receptor resistance during therapy with RU 486. The compensatory overproduction of androgens and consequently of estrogens during long-term RU 486 therapy might limit its use as a single treatment in the treatment of estrogen-dependent cancer.
Asunto(s)
Andrógenos/biosíntesis , Neoplasias Encefálicas/tratamiento farmacológico , Estrógenos/biosíntesis , Meningioma/tratamiento farmacológico , Mifepristona/efectos adversos , Hormona Adrenocorticotrópica/sangre , Adulto , Anciano , Androstenodiona/sangre , Ritmo Circadiano , Hormona Liberadora de Corticotropina , Dexametasona , Estradiol/sangre , Femenino , Humanos , Hidrocortisona/sangre , Hidrocortisona/orina , Masculino , Persona de Mediana Edad , Mifepristona/uso terapéutico , Náusea/inducido químicamente , Vómitos/inducido químicamenteRESUMEN
UNLABELLED: Insulin-like growth factor-I (IGF-I) stimulates ovarian androgen production. Insulin-like growth factor binding protein-1 (IGFBP-1) inhibits IGF actions in vitro. OBJECTIVE: To investigate the effect of oral contraceptive (OC) pills, given for 3 months, on serum gonadotropin, androgen, IGF-I, and IGFBP-1 concentrations, and glucose tolerance in seven women with polycystic ovarian disease (PCOD) and in five healthy control subjects. PATIENTS: Seven women with PCOD and five healthy control subjects. INTERVENTIONS: An oral glucose tolerance test (OGTT) was performed before and after treatment with OC. RESULTS: After treatment with OC, serum luteinizing hormone, androstenedione, and free testosterone levels decreased, and sex hormone-binding globulin concentration increased in the women with PCOD as well as in the control subjects. The cumulative response of serum insulin to OGTT was larger in the women with PCOD than in the control subjects both before and after treatment. Serum IGF-I concentration, which was unchanged during OGTT, decreased from basal level of 326 +/- 70 micrograms/L to 199 +/- 28 micrograms/L after treatment with OC in the women with PCOD, whereas no change was found in the control subjects (from 235 +/- 11 micrograms/L to 226 +/- 11 micrograms/L). Treatment with OC caused an increase of the mean basal IGFBP-1 concentration from 24 +/- 7 micrograms/L to 73 +/- 14 micrograms/L in the women with PCOD. This increase was constant during the OGTT. In the control subjects, treatment with OC did not result in any significant change in IGFBP-1 concentrations (from 44 +/- 11 micrograms/L to 61 +/- 9 micrograms/L). CONCLUSION: The combination of decreased total IGF-I concentration and increased IGFBP-1 concentration induced by OC may decrease ovarian androgen production in PCOD.
PIP: Insulin-like growth factor-I (IGF-I) stimulates ovarian androgen production. Insulin-like growth factor binding protein-1 (IGFBP-1) inhibits IGF actions in vitro. The objective of this study was to investigate the effect of oral contraceptives (OCs), administered for 3 months, on serum gonadotropin, androgen, IGF-I, and IGFBP-1 concentrations, and glucose tolerance in 7 women with polycystic ovarian disease (PCOD) and in 5 healthy subjects. An oral glucose tolerance test (OGTT) was performed before and after treatment with OCs. After treatment, serum luteinizing hormone, androstenedione, and free testosterone levels decreased, and sex hormone-binding globulin concentrations increased in the women with PCOD as well as in the controls. The cumulative response of serum insulin to OGTT was larger in women with PCOD than in the controls, both before and after treatment. Serum IGF-I concentration, which was unchanged during OGTT, decreased from a basal level of 326 +or- 70 mcg/L to 199 +or- 28 mcg/L after OC treatment in those women with PCOD, whereas no change was found in the controls (from 235 +or- 11 mcg/L to 22 +or- 11 mcg/L). Treatment with OCs caused an increase in the mean basal IGFBP-1 concentrations from 24 +or- 7 mcg/L to 73 +or- 14 mcg/L in the women with PCOD. This increase was constant during OGTT. Among the control subjects, treatment with OCs did not result in any significant change in IGFBP-1 concentrations (from 44 +or- mcg/L to 61 +or- 9 mcg/L). The combination of decreased total IGF-1 concentration and increased IGFBP-1 concentration induced by OCs may decrease ovarian androgen production in PCOD.
Asunto(s)
Proteínas Portadoras/sangre , Anticonceptivos Hormonales Orales/farmacología , Acetato de Ciproterona , Síndrome del Ovario Poliquístico/sangre , Adolescente , Adulto , Ciproterona/farmacología , Combinación de Medicamentos , Etinilestradiol/farmacología , Femenino , Prueba de Tolerancia a la Glucosa , Humanos , Insulina/sangre , Proteínas de Unión a Factor de Crecimiento Similar a la Insulina , Factor I del Crecimiento Similar a la Insulina/metabolismo , Hormona Luteinizante/sangre , Globulina de Unión a Hormona Sexual/metabolismo , Testosterona/sangreRESUMEN
The clinical performance and endocrine profiles of contraceptive vaginal rings (CVR) with an in vitro daily release rate of 15 micrograms of ethinylestradiol combined with 75, 100 or 150 micrograms 3-keto-desogestrel were evaluated. Two studies were performed; one with 11 volunteers, consisting of a control cycle, a cycle with an oral preparation (Marvelon), followed by two CVR treatment cycles, and a second study with 12 volunteers, having the same design but one CVR treatment cycle. A dose-response relationship was seen in the endocrine and clinical performance of the CVR. With CVR 75/15, ovulation occurred in two subjects, and increases in serum estradiol concentrations were seen in two additional subjects. With CVR 100/15, slight estradiol increases were seen in four subjects, but progesterone remained low. With CVR 150/15, both estradiol and progesterone serum concentrations remained low. With CVR 75/15 extra bleeding was common, but with CVR 150/15 this did not occur. No major side effects occurred, and no abnormal Papanicolaou smears or histological findings of the endometrium were found. All volunteers completed all cycles, and the three-week CVR use was generally well accepted. In conclusion, the release rate of CVR 75/15 was insufficient. A vaginal ring with a daily release rate between 100 and 150 micrograms of 3-keto-desogestrel in combination with 15 micrograms of ethinylestradiol seems suitable for contraceptive purposes, and will be further tested in larger clinical studies.
Asunto(s)
Dispositivos Anticonceptivos Femeninos , Desogestrel , Etinilestradiol/farmacología , Norpregnenos/farmacología , Progestinas/farmacología , Adulto , Androstenodiona/sangre , Deshidroepiandrosterona/sangre , Dihidrotestosterona/sangre , Relación Dosis-Respuesta a Droga , Estradiol/sangre , Femenino , Humanos , Ciclo Menstrual/efectos de los fármacos , Ovario/efectos de los fármacos , Progesterona/sangre , Testosterona/sangreRESUMEN
Evidence is provided that the fibrinolytic capacity in plasma is strongly dependent on circulating concentrations of tissue plasminogen activator rather than on concentrations of plasminogen activator inhibitor. Thus a decrease in plasma tissue plasminogen activator concentrations, as is the case in oral contraceptive users, may result in a decrease in plasma fibrinolytic capacity despite a parallel decrease in plasminogen activator inhibitor levels. It is now clear that the presence of specific intracellular receptors and a given motif in the genome are essential to mediate hormone-dependent regulation of gene expression. A computer search revealed potential estrogen and glucocorticoid-progesterone-responsive elements in the genes coding for tissue plasminogen activator, plasminogen activator inhibitor, and some other fibrinolytic variables. No convincing evidence for the presence of sex steroid receptors in endothelial cells was found, but liver cells clearly contain estrogen and androgen receptors. However, neither endothelial cells nor hepatocytes cultured in vitro showed a change in tissue plasminogen activator or plasminogen activator inhibitor synthesis on incubation with sex steroids (10(-9) to 10(-6) mol/L) for 3 days. An alternative explanation for the observed decreases in tissue plasminogen activator and plasminogen activator inhibitor concentrations in the plasma of oral contraceptive users is discussed.
Asunto(s)
Anticonceptivos Orales Combinados/farmacología , Anticonceptivos Hormonales Orales/farmacología , Fibrinólisis/efectos de los fármacos , Endotelio/efectos de los fármacos , Femenino , Humanos , Hígado/efectos de los fármacos , Receptores de Superficie Celular/efectos de los fármacos , Activador de Tejido Plasminógeno/sangreRESUMEN
The effect of a low dose triphasic oral contraceptive (OC) was evaluated during a 6-month treatment period in 41 patients (mean age, 25.4 +/- 0.7 yr) who had grade I-IV postpubertal acne and normal menses. The OC contained three dose levels of ethynyl estradiol and dl-norgestrel. Acne lesions were assessed, and serum androgen levels were measured during a control cycle and between days 17-21 of treatment cycles 1, 2, 3, and 6. Four patients dropped out after 3 months of treatment. Acne was significantly improved after the first OC cycle. After six cycles, the number of comedones had decreased by 79.6 +/- 3.2% (range, 50-100%) in 69.4% of the patients. Mean baseline levels of testosterone, 17-hydroxyprogesterone, and dehydroepiandrosterone sulfate were in the upper third of the normal range, with elevated individual values in 18.9%, 36.5%, and 26.8% of the women, respectively. Mean baseline levels of androstenedione, free testosterone (T), and 3 alpha-androstanediol glucuronide (3 alpha-diol-G) were above the normal range, with elevated individual values in 51.2%, 75.0%, and 85.4% of the patients, respectively. Sex hormone-binding globulin (SHBG) levels were below the normal range in 26.8% of the cases. At the end of the first OC cycle, there was a significant (P less than 0.01) decrease in all androgen precursors and a 2-fold increase in SHBG. Androstenedione and free T decreased into the normal range during OC intake. Serum 3 alpha-diol-G levels remained elevated, but had decreased by 34.5% at cycle 6 (P less than 0.05). These results show that the triphasic OC has significantly improved acne in postpubertal women for whom acne was the main manifestation of mild hyperandrogenic activity. The improvement in acne corresponded to a decrease in adrenal/ovarian androgens and free T, which led to a decreased metabolism to 3 alpha-diol-G, presumably by the sebaceous glands. The increase in SHBG is considered an estrogenic effect, and the triphasic formulation containing low dose dl-norgestrel is not androgenic but, rather, an estrogen-dominant formulation; as such, this product is recommended in women requiring contraception who also have idiopathic acne.
Asunto(s)
Acné Vulgar/tratamiento farmacológico , Andrógenos/sangre , Anticonceptivos Secuenciales Orales/administración & dosificación , Anticonceptivos Orales/administración & dosificación , Etinilestradiol/administración & dosificación , Norgestrel/administración & dosificación , Globulina de Unión a Hormona Sexual/análisis , Acné Vulgar/sangre , Acné Vulgar/patología , Adolescente , Adulto , Androstenodiona/sangre , Anticonceptivos Secuenciales Orales/farmacología , Relación Dosis-Respuesta a Droga , Etinilestradiol/farmacología , Femenino , Gonadotropinas Hipofisarias/sangre , Humanos , Fase Luteínica/efectos de los fármacos , Norgestrel/farmacología , PubertadRESUMEN
Epidemiologic results indicate that women who smoke cigarettes are relatively estrogen-deficient. Smokers have an early natural menopause, a lowered risk of cancer of the endometrium, and an increased risk of some osteoporotic fractures. Moreover, women who smoke may have a reduced risk of uterine fibroids, endometriosis, hyperemesis gravidarum, and benign breast disease. Several possible mechanisms for these effects have been identified. Smoking does not appear to be clearly related to estradiol levels, at least in postmenopausal women, although levels of adrenal androgens are increased. Moreover, smoking appears to alter the metabolism of estradiol, leading to enhanced formation of the inactive catechol estrogens.
Asunto(s)
Estrógenos/deficiencia , Fumar/efectos adversos , Neoplasias de la Mama/etiología , Femenino , Humanos , Masculino , Menopausia , Osteoporosis Posmenopáusica , Neoplasias Uterinas/etiologíaRESUMEN
Levonorgestrel (LNg) is known for its marked progestational/contraceptive activity. As shown in animal experiments, however, high doses of LNg are required to elicit an androgenic response; in contrast, considerably lower doses of LNg are required for antiovulatory (contraceptive) action. Thus, a large dose separation exists between androgenic and contraceptive activity. When LNg is combined with an estrogen, as in the contraceptive formulations, the androgenic response is attenuated or negated. The results of recent clinical trials have demonstrated that the androgenic activity of LNg is not expressed at contraceptive doses, particularly when LNg is combined with ethinyl estradiol (EE), as in the low-dose monophasic/triphasic formulations (monophasic [Nordette]: 150 mcg LNg/30 mcg EE; triphasic [Triphasil/Trinordiol]: six days, 50 mcg LNg/30 mcg EE; five days, 75 mcg LNg/40 mcg EE; ten days, 125 mcg LNg/30 mcg EE). Clinical evidence from several trials confirms that sex hormone-binding globulin levels are increased, plasma androgen levels are decreased, and acne is markedly improved with the use of Triphasil and Nordette, suggesting a non-androgenic profile.
Asunto(s)
Andrógenos/biosíntesis , Anticonceptivos Orales Combinados/farmacología , Norgestrel/farmacología , Ovulación/efectos de los fármacos , Congéneres de la Progesterona/farmacología , Acné Vulgar/etiología , Adolescente , Adulto , Animales , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Levonorgestrel , Masculino , Estudios Multicéntricos como Asunto , Tamaño de los Órganos , Próstata/efectos de los fármacos , Ratas , Ratas Endogámicas , Vesículas Seminales/efectos de los fármacos , Globulina de Unión a Hormona Sexual/biosíntesisRESUMEN
The goal in improving the progestational component of oral contraceptives (OCs) is to enhance the selectivity of the progestin by achieving a high degree of contraceptive efficacy while decreasing undesirable side effects associated with existing progestational agents. The androgenic activity of current progestins results in changes in lipid metabolism, particularly decreased levels of high-density lipoprotein cholesterol (HDL), which have been associated with an increased risk of coronary heart disease (CHD). A progestin with high antiovulatory activity and minimal androgenicity would offer a clear therapeutic advantage in oral contraception. Norgestimate (NGM) is a new progestin with a unique profile of biological activity that has demonstrated a high level of selectivity in preclinical assays. The present studies were conducted to confirm clinically the low androgenic activity of NGM. Norgestimate (0.25 mg) in combination with 0.035 mg ethinyl estradiol (NGM 0.25/35) was compared with 0.30 mg norgestrel combined with 0.030 mg ethinyl estradiol (Lo/Ovral) in two multicenter clinical studies. In the first study (1,261 women), HDL levels were significantly increased from baseline levels in NGM 0.25/35 subjects but were significantly decreased in Lo/Ovral subjects. Increases in low-density lipoprotein cholesterol (LDL) levels were moderate in the NGM 0.25/35 group and pronounced in the Lo/Ovral group. A favorable lipid profile in NGM 0.25/35 subjects was also reflected in the LDL/HDL ratios, which were significantly lower in the NGM 0.25/35 subjects than in the Lo/Ovral subjects. Sex hormone binding globulin (SHBG) binds androgens, preventing clinical expression of androgenic activity. As a result, elevations in SHBG levels reduce bioactive (unbound) androgen levels and decrease the potential for androgenic side effects.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Andrógenos , Anticonceptivos Orales Combinados/farmacología , Norgestrel/análogos & derivados , Acné Vulgar/inducido químicamente , Adulto , Proteína de Unión a Andrógenos/análisis , Anticonceptivos Orales Combinados/efectos adversos , Etinilestradiol/efectos adversos , Etinilestradiol/farmacología , Femenino , Humanos , Lipoproteínas/sangre , Estudios Multicéntricos como Asunto , Norgestrel/efectos adversos , Norgestrel/farmacología , Ensayos Clínicos Controlados Aleatorios como Asunto , Aumento de PesoRESUMEN
Fourteen hirsute girls, ages 12 to 22 years (mean +/- SD: 17.2 +/- 2.6 years), in whom 21-hydroxylase deficiency was excluded by a 1-hour intravenous alpha 1-24 corticotropin test, were evaluated by a 4-day dexamethasone test and then treated with a bedtime dose of dexamethasone (0.5 mg in 10 patients, 0.25 mg in four) for 0.6 to 3.4 years (1.3 +/- 0.8 years). Hirsutism decreased in four patients, did not change in nine, and increased in one. Of the 10 patients with irregular menses, only three developed regular cycles while taking dexamethasone. During long-term dexamethasone therapy, serum levels of testosterone decreased from 102 +/- 22 to 72 +/- 27 ng/dL, free testosterone from 35 +/- 11 to 19 +/- 8 pg/mL, and dehydroepiandrosterone sulfate from 396 +/- 138 to 171 +/- 101 micrograms/dL. Although free testosterone decreased to less than 15 pg/mL in eight of 14 patients with the suppression test, only four patients had free testosterone levels less than 15 pg/mL during therapy. Two of the 14 patients have had no recurrence of hirsutism or increase in serum androgens after 28 and 29 months, respectively, after dexamethasone therapy was discontinued. Oral contraceptives were given to nine patients inadequately responsive to bedtime dexamethasone therapy. The mean percent decrease of testosterone and free testosterone levels during oral contraceptive therapy was significantly greater than during long-term treatment with dexamethasone, and hirsutism lessened in all. We conclude that a single bedtime dose of dexamethasone is satisfactory only in patients who maintain serum free testosterone values less than 15 pg/mL without side effects. For other patients, either another glucocorticoid or, in most cases, ovulation suppression should be prescribed for adolescents with progressive hirsutism and elevated androgen levels.
Asunto(s)
Dexametasona/uso terapéutico , Hirsutismo/tratamiento farmacológico , 17-Cetosteroides/orina , Adolescente , Adulto , Andrógenos/sangre , Niño , Anticonceptivos Orales/uso terapéutico , Femenino , Humanos , Trastornos de la Menstruación/tratamiento farmacológico , Testosterona/sangreRESUMEN
A clomiphene citrate (CC) challenge test was used to prospectively assess future fertility potential in 51 women aged 35 or more with unexplained infertility. Baseline (day 2-3 of the menstrual cycle) and response levels (day 9-11) of follicle stimulating hormone (FSH), luteinising hormone (LH), and 17-beta oestradiol were measured before and after administration of 100 mg clomiphene on days 5-9 of the menstrual cycle. Although all the women had a normal baseline FSH, 18 had an exaggerated FSH response of 26 mIU/ml or more (over 2 standard deviations above control values); this was regarded as a diminished ovarian reserve (DOR). In the DOR group mean response FSH was 38.9 mIU/ml (SD 13.8) and in 33 women with adequate ovarian reserve (AOR) it was 11.5 (4.9) mIU/ml (p less than 0.0001). In the DOR group 1 of 18 patients and in the AOR group 14 of 33 (42%) conceived (p less than 0.05). It is suggested that despite apparently normal ovulatory cycles, the DOR group has a compromised follicular apparatus. Disparity between normal oestradiol secretory capacity of the granulosa and diminished capacity to secrete inhibin could explain the inappropriately high FSH levels in response to the CC challenge.
Asunto(s)
Fertilidad , Adulto , Gonadotropina Coriónica/uso terapéutico , Clomifeno/farmacología , Femenino , Fertilidad/efectos de los fármacos , Hormona Folículo Estimulante/sangre , Estudios de Seguimiento , Humanos , Infertilidad/tratamiento farmacológico , Hormona Luteinizante/sangre , Ciclo Menstrual , Ovario/fisiología , Ovulación/efectos de los fármacos , Embarazo , Pronóstico , Estudios ProspectivosRESUMEN
The search for major abnormalities as causes for breast cancer have not been successful, whether they have been directed to patients with this disease, different groups, or populations at risk. Anovulation or progesterone deficiency are not characteristic for those at risk for breast cancer or those patients with early breast cancer. In contrast, early-onset long-lasting ovulatory cycle function seems to be prevalent in different risk categories. Women with early menarche are additionally characterized by having higher serum estradiol and lower sex hormone-binding globulin concentrations than women with later menarche, at least during the early years of their fertile life. Estradiol is a central agent in the process of breast cancer appearance, and progesterone does not seem to have an opposing action. A decrease in the number of ovulatory cycles may exert a protective effect against breast cancer. If the decrease is affected by endocrine mechanisms maintaining breast ethelial stimulation comparable to that during the normal menstrual cycle, the protective effect would be nullified.
Asunto(s)
Andrógenos , Anovulación , Neoplasias de la Mama , Hormonas del Cuerpo Lúteo , Enfermedad , Economía , Estrógenos , Genitales Femeninos , Hormonas , Neoplasias , Ovario , Características de la Población , Progesterona , Sustancias para el Control de la Reproducción , Factores Socioeconómicos , Sistema Urogenital , Factores de Edad , Antropometría , Biología , Peso Corporal , Sistema Endocrino , Servicios de Planificación Familiar , Genitales , Obesidad , Paridad , Fisiología , Progestinas , InvestigaciónRESUMEN
Serum levels of androstenedione, dihydrotestosterone, and testosterone were determined by radioimmunoassay procedures in 25 female volunteers using subdermal levonorgestrel implants as a contraceptive. Mean serum androstenedione levels were increased after 1 and 6 months in comparison with preimplantation levels, the increase being significant only after 1 month. This could be attributed to increased production from the adrenal or ovaries and/or changes in clearance rate. Testosterone levels showed approximately 24% increase above basal values after 6 months' use of levonorgestrel implants, which was attributed to concomitant increases in androstenedione levels. The implication of these results is discussed.
Asunto(s)
Andrógenos , Anticoncepción , Anticonceptivos Femeninos , Hormonas , Inyecciones , Levonorgestrel , Sustancias para el Control de la Reproducción , Factores de Edad , Biología , Anticonceptivos , Sistema Endocrino , Servicios de Planificación Familiar , Paridad , Fisiología , TestosteronaRESUMEN
Urinary testosterone, androstanediol, ethiocolanolone, and androsterone glucuronide were determined by use of gas chromatography in four patients with carcinoma in situ of the breast. In all the patients, one or more of these hormones were higher than normal. This finding supports previous reports from our laboratory of increased androgen excretion in patients with fibrocystic disease or infiltrating carcinoma of the breast. Carcinoma in situ arose while the four patients were taking oral contraceptives. The progestational component of the pill, a nonderivative of testosterone, may carry with it some androgenic properties. This fact and the discovery of increased androgen excretion levels in these four patients led us to suppose that androgens could play a role in the development of breast cancer.
Asunto(s)
Andrógenos/orina , Neoplasias de la Mama/orina , Carcinoma in Situ/orina , Anticonceptivos Orales/efectos adversos , Adolescente , Adulto , Neoplasias de la Mama/inducido químicamente , Carcinoma in Situ/inducido químicamente , Femenino , Humanos , Persona de Mediana Edad , RiesgoRESUMEN
Plasma concentrations of luteinizing hormone (LH), follicle-stimulating hormone (FSH), prolactin (PRL), testosterone (T), and 17 beta-estradiol (E2) have been measured in men complaining of infertility in comparison with men of proven fertility. Subgrouping of patients was achieved on the basis of the presence or absence of sperm in the ejaculate and further by the concentration of sperm or by testicular score. The levels of plasma LH, FSH, PRL, and T were found to be significantly different in the fertile men, compared with both infertile men with sperm in their ejaculates and azoospermic men. There were no significant differences between the groups for E2. There appeared to be an inverse relationship between LH concentrations and sperm count in both fertile and infertile men. FSH levels did not vary significantly in the fertile men in relation to sperm count grouping but were significantly less than those found for the infertile men with sperm. Azoospermic patients with high testicular scores had FSH levels indistinguishable from those of the fertile men. The results are discussed in terms of testicular abnormalities and on the interrelationship between the hormones examined.
PIP: Plasma concentrations of luteinizing hormone (LH), follicle stimulating hormone (FSH), prolactin (PRL), testosterone (T), and 17beta estradiol (E2) have been measured in men complaining of infertility in comparison with men with proven fertility. Subgrouping of patients was achieved on the basis of the presence or absence of sperm in the ejaculate and further by the concentration of sperm of by testicular score. The levels of plasma LH, FSH, PRL, and T were found to be significantly different in the fertile men, compared with both infertile men with sperm in their ejaculates and azoospermic men. There were no significant differences between groups for E2. There appeared to be an inverse relationship between LH concentrations and sperm count in both fertile and infertile men. FSH levels did not vary significantly in the fertile men in relation to sperm grouping count but were significantly less than those found for infertile men with sperm. Azoospermic men with high testicular scores had FSH levels indistinguishable which were from those of fertile men. The results are discussed in terms of testicular abnormalities and the interrelationship between the hormones examined.
Asunto(s)
Fertilidad , Hormonas Esteroides Gonadales/sangre , Hormonas Adenohipofisarias/sangre , Testículo/fisiología , Estradiol/sangre , Hormona Folículo Estimulante/sangre , Humanos , Hormona Luteinizante/sangre , Masculino , Prolactina/sangre , Recuento de Espermatozoides , Testosterona/sangreRESUMEN
22 adult females with therapy-resistant acne vulgaris were treated for 12 months with Diane, a drug containing cyproterone acetate and ethinylestradiol. Treatment was withdrawn in 7 patients because of side-effects of lack of of effect. In the remaining 15 patients, the treatment had extremely promising results, from 70 to 90% improvement of the acne. In a remarkably high number of patients, the androgen production, measured by the urinary excretion of fractional 17-ketosteroids, was elevated. None of these patients had signs of endocrinological diseases, in particular no cases of hirsutism of Stein-Leventhal syndrome were found. The current concept of the course of acne is that the conversion in the skin of testosterone to dehydrotestosterone is increased. The finding of an elevated urinary excretion of androgenic substances in this group of acne patients indicates that the pathogenesis is far more complicated.
Asunto(s)
Acné Vulgar/tratamiento farmacológico , Anticonceptivos Masculinos/uso terapéutico , Ciproterona/análogos & derivados , 17-Cetosteroides/orina , Acné Vulgar/metabolismo , Adulto , Ciproterona/uso terapéutico , Acetato de Ciproterona , Combinación de Medicamentos , Etinilestradiol/uso terapéutico , Femenino , Humanos , Hidrocortisona/sangre , Testosterona/sangreRESUMEN
Elevated concentrations of peptide hormones have been described previously in human breast fluid. In the current study, the levels of cortisol, progesterone, testosterone, dihydrotestosterone, androsterone, androsterone sulfate, dehydroisoandrosterone, dehydroisoandrosterone sulfate, estradiol, estrone, estradiol sulfate, and estrone sulfate were measured. The levels of the four 17-ketosteroids and the two estrogen sulfates were markedly elevated over the plasma level, while that of the other compounds was the same or only slightly higher than the plasma levels of the same compounds.
PIP: As part of a program to explore whether a relationship existed between the compounds present in breast cyst fluid and the risk for breast cancer, concentrations of a wide variety of hormones, enzymes, tumor-associated antigens, and ions in breast cyst fluid were determined. In this report, the concentrations of steroid hormones in cyst fluid samples from the same population used for previously published studies of peptide hormone concentrations were measured. This study determined the levels of cortisol, progesterone, testosterone, dihydrotestosterone, androsterone, androsterone sulfate, dehydroisoandrosterone, dehydroisoandrosterone sulfate, estradiol, estrone, estradiol sulfate, and estrone sulfate. In previous studies, levels of peptide hormones were shown to be elevated in breast cyst fluid, and in this study, the levels of the 4 17-ketosteroids and the 2 estrogen sulfates were markedly elevated in the breast cyst fluid over the plasma level. The concentrations of the other compounds were either the same or only slightly higher than plasma levels of the same compounds. To date, however, no correlation has been obtained between the occurrence of breast cancer and levels of any of these assayed hormones.
Asunto(s)
Andrógenos/metabolismo , Enfermedades de la Mama/metabolismo , Estrógenos/metabolismo , Enfermedad Fibroquística de la Mama/metabolismo , Androsterona/metabolismo , Quistes/metabolismo , Exudados y Transudados/metabolismo , Femenino , Humanos , Sulfatos/metabolismo , Testosterona/metabolismoRESUMEN
To explore the possibility that the wide variation in bone loss among oophorectomised women might be due to differences in adrenal androgens or their biosynthetic pathways, 18 women (10 with very fast and 8 with very slow bone loss) were selected. Serum levels of nine adrenal steroids, including the major androgens and cortisol, were measured under basal conditions and after overnight suppression followed by acute corticotropin stimulation. In addition, basal serum oestrone, oestradiol, dehydroepiandrosterone sulphate, sex-hormone-binding-globulin, corticosteroid binding globulin, and urinary free cortisol were measured. The only significant differences found were that women who lost bone rapidly had significantly higher urinary free-cortisol excretion (p less than 0.001) and a paradoxically diminished cortisol response to corticotropin. These data make it unlikely that endogenous adrenal androgens or oestrogens are a major factor in preventing bone loss after cessation of ovarian function; cortisol by its catabolic effect, however, may be a significant factor in causing osteoporosis.
PIP: To examine the influence of differences in adrenal androgens or their biosynthetic pathways in the wide variations in bone loss among oophorectomized women, 18 women were selected for study. 10 women had very fast bone loss and 8 had very slow; 5 other women who had been on estrogen replacement therapy were also selected. Difference between the fast and slow losers in urinary free cortisol excretion was highly significant; the levels were higher in fast loser (P-.001). Treated patients had values similar to those of slow losers. No difference was detected between fast and slow losers in basal plasma values for dehydro-epiandrosterone (DHEA), adione, adiol, testosterone, DHEA-SO4, estrone, estradiol, cortisol, sex hormone binding globulin, and corticosteroid binding globulin. The only significant differences found were that women who lost bone rapidly had significantly higher free cortisol excretion and a paradoxically diminished cortisol response to corticotropin. It is, therefore, unlikely that endogenous adrenal androgens or estrogens are a major factor in preventing bone loss after cessation of ovarian function; however, cortisol, because of its catabolic effect may be a significant factor in causing osteoporesis. The serum levels of the 9 adrenal steroids were measured under basal conditions and after overnight suppression followed by acute corticotropin stimulation.
Asunto(s)
17-Cetosteroides/metabolismo , Andrógenos/metabolismo , Castración/efectos adversos , Estrógenos/metabolismo , Hidroxiesteroides/metabolismo , Osteoporosis/etiología , Adulto , Androstenodioles/metabolismo , Androstenodiona/metabolismo , Deshidroepiandrosterona/metabolismo , Estradiol/metabolismo , Estrona/metabolismo , Femenino , Humanos , Hidrocortisona/metabolismo , Persona de Mediana Edad , Osteoporosis/metabolismo , Globulina de Unión a Hormona Sexual/metabolismo , Testosterona/metabolismoRESUMEN
Women with ovarian hyperthecosis were studied and found to have a plasma testosterone production rate of 2.1 mg/day, a value eight times greater than that of nonhirsute, ovulatory women. The severity of hirsutism and virilization in these women was more closely correlated with the amount of testosterone produced than with plasma testosterone concentrations. The mean plasma production rates of androstenedione in these women, 8.6 mg/day, was more than three times that found in young women with no evidence of androgen excess. There was a marked gradient between ovarian and peripheral venous plasma concentrations for both C19 steroids. Following ovarian wedge resection or oophorectomy, there was a precipitous fall in the peripheral venous concentrations of these steroids. These observations support the view that the major source of excess androstenedione and testosterone secretion in these subjects was the ovaries. The rate of estrone formation in these women, 106-345 microgram/day, was the result of extraglandular aromatization of plasma androstenedione.
PIP: 6 women with ovarian hyperthecosis were studied and found to have plasma testosterone production rates of 2.1 mg/day, 8 times greater than normal. Androstenedione production ranged from 3.9 to 13.2 mg/day, compared with 2.6 for normal women. The severity of hirsutism and virilization was more closely correlated with amount of testosterone produced than with plasma testosterone concentrations. There was a marked gradient between ovarian and peripheral venous plasma concentrations for both steroids. 106-345 mcg/day estrone was formed from extraglandular aromatization of plasma androstenedione. There were no significant deviations from normal for ACTH and cortisol concentrations. Ovarian wedge resection or oophorectomy was followed by immediate fall in the peripheral venous concentrations of androstenedione and testosterone, supporting the view that the ovaries were the source of the excess secretion.