Phase III clinical trial with a new oral contraceptive containing 150 micrograms desogestrel and 20 micrograms ethinylestradiol.

Results are presented of a Phase III international multicentre trial to study the effect of a new low-dose oral contraceptive (OC) containing 20 micrograms ethinylestradiol and 150 micrograms desogestrel (Mercilon) regarding efficacy, cycle control, blood pressure, and acceptability. Altogether 1,684 women from 12 European countries were included in the study. Four pregnancies occurred, 3 of them patient failures, one tablet failure. The overall Pearl Index was 0.20. The frequency of irregular bleeding was comparable to that recorded with other commonly used low-dose OCs. No serious side effects occurred. The incidence of the most frequently reported subjective side effects--headache, nausea and breast tension--was already low after the first cycle of treatment and decreased to below pretreatment levels with continued use. There was a small increase in mean body weight, which was confined essentially to young women. The preparation did not affect the mean systolic or diastolic blood pressure. This new preparation has thus proved to be an effective, safe and well-accepted ultra low-dose oral contraceptive.     

Ontogeny of MAP2 and GFAP antigens in primary cultures of embryonic chick brain. Effect of substratum, oxygen tension, serum and Ara-C

Brain cells from embryonic chick (stage 28-29) were cultivated for 16 days under serum-free conditions. Nerve cells were found to mature during the first 7 days in culture, as indicated by the presence and developmental pattern of the relative amount of dendritic-specific microtubule-associated protein type 2 (MAP2). Maximal amounts of MAP2 antigen were found to be directly correlated with the number of cells plated out. Astroglia cell proliferation and differentiation, as measured by the amounts of glial fibrillary acidic protein (GFAP), were found to stabilize after a certain astrocyte cell density was reached. Variation in culture plate coating procedure, oxygen tension and addition of serum or of the cytostatic drug Ara-C were found to differently affect viability and maturation processes of astroglia and of nerve cells. Moreover, optimal culture conditions for long-term brain cell cultures are described.     

In vitro studies on the effect of delaminated a-C:H film fragments on bone marrow cell cultures

Amorphous hydrogenated carbon (a-C:H) films have many outstanding properties required for a protective coating material on load bearing medical implants. Recently, titanium doped a-C:H films have been evaluated regarding their effects on bone marrow cell cultures. But many materials that are well-tolerated in bulk form are able to induce toxic reaction if present particulate form. In order to further assess biocompatibility aspects of these two coatings, film delamination has been mimicked in exposure to fluids. In the present study, particles from a-C:H, a-C:H/Ti and a-C:H-a-C:H/Ti bilayer films were added to bone marrow cell cultures in vitro. The results showed that plain a-C:H and to a certain extent a-CH/Ti particles were inert. Both kinds of particles did not significantly stimulate the osteoclast-related enzyme tartrate resistant acid phosphatase (TRAP). A slight increase in cell proliferation and total culture TRAP was found in cultures treated by a-C:H-a-C:H/Ti bilayer films. Latter effect can probably be traced back by the relative high percentage of small particles of a size of around 2 microm. However, if corrected by the cell number also no differences between particle-treated and untreated control cultures could be found, indicating the absence of a toxic effect from delaminated a-C:H coatings.     

Grooves affect primary bone marrow but not osteoblastic MC3T3-E1 cell cultures

To elucidate the influence of microtextures on bone cell performance, primary adult rat bone marrow cells (RBMC) and osteoblastic MC3T3-E1 cells were cultured on tissue culture pretreated plates to which grooves at different density were applied. RBMC cells were found to be significantly affected by grooves in the substratum in contrast to osteoblastic MC3T3-E1 cells, taking culture morphology, total cell number, cell mass, and cell activity (MTT-dehydrogenase), parameter for differentiation of osteoblast progenitor cells into (pre-)osteoblasts (alkalinephosphatase activity, ALP) and tartrate-resistant acid phosphatase (TRAP) activity as indices. TRAP is located in lysosomes and secretory granules mainly although not solely in osteoclasts. By applying grooves to and/or by chemical treatment of unpretreated pure polysterene plates it could be concluded that the effects on RBMC cells were evoked not only by the presence of grooves but also by the surface chemistry of the grooved and ungrooved surface areas.     

Desogestrel: using a selective progestogen in a combined oral contraceptive

Desogestrel is the most selective progestogen used in oral contraceptives (OCs). The clinical characteristics of the monophasic combined OC containing 150 g desogestrel and 30 g EE per tablet (Marvelon) are in accordance with the strong progestogenic and minimal androgenic effects of desogestrel: a very high contraceptive efficacy is combined with minimal and, in the case of lipid metabolism, even potentially positive effects on metabolic parameters.Through increasing the plasma levels of sex hormone binding globulin, and thereby decreasing the plasma levels of free testosterone, the desogestrel-containing OC also has substantial beneficial effects on acne.

---

Resumen El desogestrel es la progesterona más selectiva empleada en los anticonceptivos orales. Las características clínicas de este anticonceptivo combinado monofásico que contiene 150 g de desogestrel y 30 g EE por comprimido (Marvelon) están de acuerdo con los efectos progestágenos potentes y andrógenos mínimos del desogestrel: su alta eficacia anticonceptiva se combina con efectos minimos sobre los parámetros metabólicos, y hasta potencialmente positivos en el caso del metabolismo de los lípidos.Al aumentar los niveles plasmáticos de la globulina que enlaza las hormonas sexuales, y disminuyendo así los niveles plasmáticos de la testosterona libre, los anticonceptivos orales que contienen desogestrel tienen un considerable efecto benéfico sobre el acné.

---

Resumé Le désogestrel est la progestérone sélective la plus utilisée dans les contraceptifs oraux. Les caractéristiques cliniques de ce contraceptif combiné monophasique contenant 150 g de désogestrel et 30 g EE par comprimé (Marvelon) sont conformes aux effets progestatifs puissants et androgènes minimes du désogestrel: sa haute efficacité contraceptive se combine avec des effets sur les paramètres métaboliques qui sont minimes, et même potentiellement positifs dans le cas du métabolisme des lipides.En augmentant les niveaux plasmatiques de la globuline liant les hormones sexuelles, et en diminuant de ce fait les niveaux plasmatiques de la testostérone libre, les contraceptifs oraux contenant du désogestrel ont un effet bénéfique considérable sur l'acné.

---

---

This paper is based on a presentation given at the Seventh International Meeting of the Society for the Advancement of Contraception, which was held in Singapore on 4–11 November, 1990.