Galactorrea e hiperprolactinemia en una mujer en tratamiento con anticonceptivos / Galactorrhea and hyperprolactinemia in a woman under contraceptive treatment

Un 20-25% de las mujeres tiene galactorrea en algún momento de su vida. Es una situación clínica que debe manejar el médico de Atención Primaria. La secreción elevada de prolactina es una causa frecuente de galactorrea. La clínica típica de la hiperprolactinema es la presencia de infertilidad, oligoamenorrea y galactorrea. Describimos un caso clínico que es interesante en varios aspectos. Los niveles de prolactina sérica pueden ser orientativos de la causa de la hiperprolactinemia. El manejo de las elevaciones poco importantes de la prolactina es muchas veces conservador, retirando medicación y con pruebas de imagen y de laboratorio espaciadas. La coincidencia de hiperprolactinemia y lesión identificable en una prueba de imagen no siempre es indicativa de adenoma secretor de prolactina (AU)

About 20-25% of women suffer galactorrhea at some timein their lives. It is a clinical situation that should be treatedby the Primary Care physician. Elevated secretion of prolactinis a frequent cause of galactorrhea. The typical symptomsof hyperprolactinema are presence of infertility, oligoamenorrheaand galactorrhea. We describe a clinical case that isof interest in several aspects. The serum prolactin levels maybe orientative of the cause of the hyperprolactinemia. Managementof the unimportant elevations of prolactin is oftenconservative, withdrawing medication and with imagingtests and spaced laboratory tests. Coincidence of hyperprolactinemiaand identifiable lesion in an imaging test is not alwaysindicative of prolactin secretory adenoma (AU)

Evaluación de la potencia hormonal del anticonceptivo inyectable mensual de dihidroxiprogesterona acetofenico 150 mg y estradiol enantato 10 mg, comparativamente con tratamientos anticonceptivos orales

Se realizó un estudio retrospectivo, comparativo, abierto en 58 mujeres voluntarias del Centro de Planificación Familiar, PROFAMILIA, de Santafé de Bogotá, Colombia. La potencia hormonal del anticonceptivo inyectable mensual constituido por Dihidrixiprogesterona Acetofénido (DHPA), 150 mg y Estradiol Enantato (EEn), 10 mg, fue comparada con la de otros anticonceptivos de uso habitual (píldoras de Etinilestradiol (EE), 0.050 mg y Levonorgestrel (LNG), 0.250 mg; EE, 0.030 mg, LNG, 0.150 mg y métodos no hormonales), mediante la determinación de triglicéridos, HDL/DL colesterol, cobre, ceruloplastia, cortisol total y libre, CBG, testosterona total y libre y SHBG en el suero de usuarias crónicas. Las usuarias de métodos no hormonales fueron el grupo de control. En los exámenes de laboratorio, los niveles de triglicéridos fueron más altos y los de testosterona total y libre más bajos en las mujeres que emplean DHPA 150 mg + EEn 10 mg y en las que utilizan píldoras. Tales modificaciones fueron levemente menores en el grupo que emplea el inyectable. Los efectos de DHPA 150 mg + EEn 10 mg sobre cobre, ceruloplasmina, CBG, cortisol libre y total y SHBG fueron escasos o nulos, en comparación con el grupo no hormonal. En cambio las píldoras, inclusive las microdosificadas, mostraron modificaciones de todas esas variables, altamente significativas frente al inyectable (p 0.01) y a los métodos no hormonales (p 0.01), sin que haya diferencias entre éstos últimos. Los resultados sugieren que la potencia hormonal de DHPA 150 mg + EEn 10 mg no es mayor que la de las microdosis orales habituales. Por otro lado, no ofrecen indicios de que ésta fórmula esté sobredosificada no produzca acumulación de efectos en el organismo. Estos hallazgos deben ser tenidos en cuenta al considerar la seguridad del inyectable a largo plazo

Multicentred clinical study of the metabolic effect of the monthly injectable contraceptive containing dihydroxyprogesterone acetophenide 150 mg + estradiol enanthate 10 mg.

The metabolic effect of the monthly injectable contraceptive containing dihydroxyprogesterone acetophenide (DHPA) 150 mg + estradiol enanthate (EEn) 10 mg was compared to that of other regularly used contraceptive methods (pills containing: ethinylestradiol (EE) 0.050 mg + levonorgestrel (LNG) 0.250 mg, EE 0.030 mg + LNG 0.150 mg; EE 0.030/0.040/0.030 mg + LNG 0.050/0.075/0.0125 mg; norethisterone enanthate (NEE) 200 mg i.m.; non-hormonal methods). Serum triglycerides, HDL/LDL-cholesterol, copper, ceruloplasmin, total and free cortisol, CBG, total and free testosterone and SHBG in chronic users were determined. A total of 237 women took part in this study. Taking users of non-hormonal methods as control, triglyceride levels were higher, and total and free testosterone levels were lower in women using DHPA 150 mg + EEn 10 mg and in those taking contraceptive pills (p less than 0.05 - 0.01). Such modifications were slightly less in the group using the injectable. The effects of DHPA 150 mg + EEn 10 mg on HDL/LDL-cholesterol copper, ceruloplasmin, CBG, total and free cortisol and SHBG were rare or non-existent. Nevertheless, the contraceptive pills (even the low-dose formulations) correlate with modifications of all those variables, which were highly significant in comparison with the injectable (p less than 0.01) and with non-hormonal methods (p less than 0.01); there were no differences between the last two methods. The results suggest that the metabolic effect of DHPA 150 mg + EEn 10 mg is not higher than that of the commonly used oral contraceptives. On the other hand, they do not suggest that the dose contained in this injectable is exaggerated. There is no evidence that it produces accumulation of effects in the organism. These findings should be taken into account when referring to the long-term safety of this injectable.

Role of actin in the responses of adrenal cells to ACTH and cyclic AMP: inhibition by DNase I.

Erythrocyte ghosts were loaded with pancreatic DNase I and fused with Y-1 adrenal tumor cells to test the possibility that this enzyme might inhibit the steroidogenic responses of the cells to ACTH and cyclic AMP. Fusion of erythrocyte ghosts loaded with DNase I, but not those containing albumin, ovalbumin, boiled DNase I, or DNase I with excess G-actin, inhibited the increase in production of 20 alpha-dihydroprogesterone produced by ACTH and dibutyryl cyclic AMP; inhibition was concentration-dependent with 50% inhibition by 3 X 10(7) molecules of DNase I per cell. It was found that inhibition by DNase I was exerted at the step in the steroidogenic pathway at which cholesterol is transported to mitochondria where steroidogenesis begins. This was shown by measuring transport of cholesterol into the inner mitochondrial membrane, by measuring the production of pregnenolone by isolated mitochondria and by demonstrating that DNase I was without effect on the conversion of pregnenolone to 20 alpha-dihydroprogesterone (an end-product of steroid synthesis). The actin content of Y-1 cells was measured by two methods based upon inhibition of DNase I and by SDS gels following centrifugation. The cells were found to contain 2-3 X 10(7) molecules of actin per cell of which two-thirds is present as G-actin. Since DNase I is known to bind to G-actin to give a one to one complex, these and other findings suggest that at least some of the G-actin in the cells may be necessary for the steroidogenic responses to ACTH and cyclic AMP.

Tixocortol pivalate, a corticosteroid with no systemic glucocorticoid effect after oral, intrarectal, and intranasal application.

Tixocortol pivalate is a corticosteroid with topical anti-inflammatory activity equal to that of hydrocortisone. It was evaluated in a group of 18 normal subjects to determine whether it exerted any systemic glucocorticoid activity after single oral or intrarectal doses and after short-term dosing by the intranasal route. Effects of tixocortol pivalate were compared to those of oral dexamethasone and intrarectal betamethasone 21-phosphate. By the three routes, tixocortol pivalate does not induce any changes in plasma cortisol, leukocyte counts (neutrophils, lymphocytes, monocytes, eosinophils), blood glucose, or 24-hr urinary excretion of sodium and potassium, whereas there were changes after dexamethasone and betamethasone. Tixocortol pivalate, however, increased urinary free cortisol-like substances. It is concluded that tixocortol pivalate given for short periods by nonparenteral routes does not induce a measurable systemic glucocorticoid effect.

Pharmacological study of a new anti-inflammatory steroid, tixocortol pivalate (JO 1016).

Some pharmacological activities of pregn-4-ene-3,20-dione-21-thiol-11 beta,17 alpha-dihydroxy-21-pivalate (tixocortol pivalate, JO 1016 Pivalone), a new steroidal anti-inflammatory compound, are described. The anti-inflammatory activity of tixocortol pivalate has been clearly demonstrated in various tests using adrenalectomised and intact animals. Of particular interest is the dissociation of its local and systemic activities. Comparison with hydrocortisone acetate indicates a similar or greater anti-inflammatory activity, by either the local or topical routes, but tixocortol pivalate is between 60 and 300 times less active than hydrocortisone acetate after oral or subcutaneous administration. Glucocorticoid activity was only detected at very high oral doses of tixocortol pivalate and the highest tested subcutaneous dose (300 mg/kg) failed to induce significant activity. Hydrocortisone acetate exerted glucocorticoid effects at much lower doses. It is possible therefore the local or topical use of tixocortol pivalate in therapy may not cause the unwanted side effects of many of the corticosteroids in current use.

A comparison of the effects of tixocortol pivalate (JO 1016), beclomethasone dipropionate and hydrocortisone acetate on the activation of lymphocytes.

A comparative study was made of the effects of hydrocortisone acetate, beclomethasone dipropionate and a corticosteroid substitute (pregn-4-ene-3,20-dione-21-thiol-11 beta,17 alpha-dihydroxy-21-pivalate, tixocortol pivalate, JO 1016, Pivalone) on lymphocyte activation. The response measured in vivo was the production of heamagglutinating antibody by mice in response to immunization with sheep erythrocytes. The in vitro response tested was the blastocytic transformation of T cells in mixed lymphocyte culture. All three compounds suppressed T cell activation in vitro. Tixocortol pivalate however, was non-toxic and non-immunosuppressive when administered to mice, in contrast to hydrocortisone acetate and beclomethasone dipropionate, which were toxic and immuno-suppressive at the highest dose levels tested. These results indicated that tixocortol pivalate would, by virtue of its low toxicity and absence of general immunosuppression, have potential advantages over both hydrocortisone acetate and beclomethasone dipropionate in the topical treatment of allergic conditions of mucous membranes.

A comparison of the effects of tixocortol pivalate (JO 1016), hydrocortisone acetate and beclomethasone dipropionate on the phagocytosis and lysis of microorganisms by alveolar macrophages.

A comparison was made of the ability of guinea pig alveolar macrophages, which had been pretreated with hydrocortisone acetate, beclomethasone dipropionate or a corticosteroid substitute pregn-4-ene-3,20-dione-21-thiol-11 beta,17 alpha-dihydroxy-21-pivalate (tixocortol pivalate, JO 1016, Pivalone), to phagocytose and lyse Staphylococcus aureus or Candida albicans. The three drugs had different patterns of effect on phagocytosis and lysis. Hydrocortisone acetate had little effect on the phagocytosis of Staph. aureus at any dose level tested, but the two higher concentrations slightly inhibited intracellular lysis; phagocytosis of C. albicans was inhibited initially but increased at 5 h. Both beclomethasone dipropionate and tixocortol pivalate caused an initial stimulation of phagocytosis and lysis of Staph. aureus. Ingestion of C. albicans was increased in macrophages pretreated with beclomethasone dipropionate, but their fungicidal activity was unchanged. Pretreatment with tixocortol pivalate stimulated the initial phagocytosis of C. albicans but continued uptake on prolonged incubation was inhibited. Lysis of the ingested organisms was not markedly affected. Since the production of any effect on the phagocytic and lytic activity of alveolar macrophages required much higher levels of tixocortol pivalate than of either of the other two drugs, it is suggested that in clinical use correspondingly higher doses of tixocortol pivalate could be given without danger of affecting either phagocytic activity or the immune response.

A comparison of the effects of tixocortol pivalate (JO 1016), hydrocortisone acetate and beclomethasone dipropionate on collagen synthesis and degradation.

The effects of a corticosteroid substitute pregn-4-ene-3,20-dione-11 beta,17 alpha-dihydroxy-21-pivalate (tixocortol, JO 1016, Pivalone), hydrocortisone acetate and beclomethasone dipropionate on collagen metabolism in mouse calvariae were compared by histological and biochemical determination of collagen content, and by radio-assays of collagenase and collagenase inhibitor. Hydroxyproline assay revealed dose-related increases in collagen content/wet wt. tissue. These were greatest in explants treated with beclomethasone dipropionate, tixocortol pivalate being effective only at much higher concentrations than the other 2 drugs. Hydrocortisone acetate and beclomethasone dipropionate stimulated collagenase production at the lowest levels tested whereas tixocortol pivalate was only slightly stimulatory at the highest treatment level. These results suggest that in clinical use tixocortol pivalate would be much less likely than hydrocortisone acetate or beclomethasone dipropionate to cause degenerative changes in connective tissue.

[Local corticoid therapy in pediatrics]. / Lokale Kortikoid-Therapie in der Kinderheilkunde.

During 1978 I carried out a clinical trial in my pediatric practice with the new corticoid dermaticum Alfason, which contains the active substance hydrocortisone-17 abutyrate--an ester of hydrocortisone not previously used therapeutically. To begin with Alfason was given in an open trial to 100 children and later, because of the favourable results obtained, it was employed in another group of 100 children in a double-blind trial against a fluorinated corticoid, a substance which up to then I had most often prescribed. The results showed a good to very good effect in over 90% of the cases treated with either drug, there was no substance related statistical difference. According to the literature the ratio of success regarding side effects is particularly favourable for Alfason so that its use in the treatment of corticoid-requiring dermatoses in childhood can be recommended.

[Norethisterone enantate as a tricyclical contraceptive. Comparative study]. / Enantato de noretisterona como contraceptivo tricíclico. Estudio comparativo.

PIP: A clinical comparative study between treatment with norethisterone enanthate, and treatment with estradiol enanthate and dehydroxiprogesterone was done to study the differences in effectiveness, changes in menstrual cycle, and side effects of the 2 preparations. Duration of investigation was of 15 months, for a total of 824 cycles. Among the 35 patients treated with norethisterone enanthate there were no pregnancies, and the drug was well accepted. There were a few cases of amenorrhea and of spotting; both manifestations disappeared spontaneously. In 65% of patients the menstrual cycle was longer than usual. 25 patients were treated with the bihormonal preparation; there was 1 pregnancy. Cycles were very close together, and lasted about 6-8 days. There were a few cases of spotting. Side effects were similar with both treatments, and never serious.^ieng

Effect of some progestational steroids on lactation in Egyptian women. I. Milk yield during the first year of lactation.

PIP: The effect of monthly injectios of 300 mg Depo-Provera or 150 mg Deladroxone, and of daily oral administration of .5 mg chlormadinone acetate or .3 mg quingestanol acetate on lactation was studied in Egyptian women during the 1st year of lactation. Women receiving Depo-Provera had the highest milk yield, followed by those taking Deladroxone and quingestanol acetate. The milk yields while taking these hormonal preparations were higher than in untreated controls. However, those women taking chlormadinone acetate had lower milk yields than untreated controls. The increased milk yield is probably due to the progestagenic activity, and minimal estrogenicity, of these drugs.^ieng

[Response of peripheral receptors to the parenteral administration of an association of dihydroxyprogesterone acetophenide and estradiol-3 benzoate-17-n-butyrate. Preliminary note]. / La risposta dei recettori periferici alla somministrazione parenterale dell'associazione diidrossiprogesterone acetofenide estradiolo-3-benzoato-17n-butirrato. Nota preventiva

PIP: The basal temperature curves, cervical mucus crystallation, endocrin e colpocytology, and endometrial cytology (Endo-Cyte) in 11 women over 30 cycles was determined following the im administration on the 8th day of the cycle of an estroprogestinic combination of 150 mg of dihydroxyprogesterone acetophenide and 10 mg of estradiol-3-benzoate-17-n-butyrate. The findings confirmed the antiovul atory action of the preparation, the absence of unwanted side effects, s ecretory transformations in the endometrium, the normality of the menstrual cycle, and the advantages associated with a single monthly administration.^ieng