[Acquired angioneurotic edema induced by hormonal contraception]. / Oedème angio-neurotique acquis induit par la contraception hormonale.

OBJECTIVE: Although frequently pointed out in the aetiology of chronic angioedema or chronic abdominal pain, food allergy is frequently a diagnosis for lack of anything better, as exemplified by disappointing results of eviction regimens. This has resulted in the search for other aetiologies, such as an iatrogenic effect of oral contraceptives. METHODS: Detailed medical history was obtained on 38 young women, aged a mean of 26 years, experiencing chronic angioedema initially ascribed to food hypersensitivity, but in whom a deficit in C1 inhibitor was demonstrated. We investigated the effects of oral contraception on their level of C1-INH, functional C1-INH assay and their clinical symptoms. RESULTS: An interruption of oral contraception induced an increase of the C1-INH level from 0.201 to 0.224 g/L (p < 0.002) and of the C1-INH functional assay fom 0.396 to 0.702 U (p < 0.0001), associated with a recovery or a marked improvement of the clinical symptoms formerly ascribed to food allergy. The replacement of the initial contraception containing ethinyloestradiol by a progestogen maintained or even improved their clinical and biological state. CONCLUSION: Exogenous estrogen such as those contained in most oral contraceptive may play an iatrogenic role in the aetiology of chronic angioedema.

[Compared action of norethindrone and various steroids on Müller ducts of the female chick embryo]. / Action comparée de la noréthindrone et de divers stéroïdes sur les canaux de Müller de l'embryon femelle de Poulet.

Treatment of female chick embryo with norethindrone (NET), a potent progesterone-like steroid, caused caudal agenesia and cephalic regression of Mullerian ducts as the normal regression induced by anti-Mullerian-hormone in the male embryo. The comparative study of five other progesterone-like steroids shows that only lynestrenol which is metabolized into NET at least in man, possesses the same properties as NET. The four others, i.e. medroxyprogesterone, medrogestone, norgestrienone and 17 alpha hydroxyprogesterone are only able to induce agenesia, an unspecific property, which was observed with many steroidal hormones, as norethandrolone here studied.

[Hereditary angioneurotic edema. Recent progress in diagnosis and treatment. Importance of a national registry]. / L'oedème angioneurotique héréditaire. Progrès récents dans le diagnostic et le traitement. Intérêt d'un registre national.

The hereditary angioneurotic oedema is an exceptional disease of deadly risk from glottic oedema. The diagnosis is based on a very low serum C4, with collapsed C1 INH for a patient who has repeated attacks of Quincke's oedema or pseudo occlusive digestive crisis. These crisis are prevented by taking anabolic steroids and must be treated when they are serious by intravenous C1 INH. The recent contributions of the immunogenetic and the interest of a national registry are underlined.

[Estrogen-progestogen agents and megaloblastic anemia]. / Oestro-progestatifs et anémie mégaloblastique.

TwO cases of megaloblastic anaemia, of which one was very severe, occurring in women who had been taking oestrogen-progestogen oral contraception over a long period of time, are reported. The authors take the opportunity, after having reviewed the literature, of pointing out the role of oestro-progestogen products in bringing about vitamin deficiencies. They discuss how and where oestrogen-progestogen products work on folic metabolism and emphasize that there is an associated factor which starts off the deficiencies.

Three-year experience with NORPLANT subdermal contraception.

NORPLANTTM (Laboratorios Gutfol, S.A., Mexico City, Mexico) subdermal implants containing levonorgestrel were accepted by 816 women in a two-phase study initiated in 1975 and augmented in 1978. Through 3 years of first-segment use, acceptors experienced five pregnancies, a cumulative net rate of 0.7 per 100, and a gross pregnancy rate of 1.1 per 100. First-segment continuation at 3 years was at the rate of 44.6 per 100, an annual average of 76 per 100. NORPLANT users experienced irregular menstruation, with high interindividual variation, but with normal average numbers of bleeding days and of bleeding episodes. Hemoglobin levels increased moderately during implant use. The incidence of systolic blood pressure readings above 145 mm Hg or diastolic readings above 95 mm Hg was similar to that observed among users of the TCu 200 intrauterine device enrolled under the same selection criteria in the same clinics between the two phases of the NORPLANT study. Comparative data on pregnancy and other rates are also given for these intrauterine device acceptors.

Experimental study of cervical blockage induced by continuous low-dose oral progestogens.

An investigation correlating scanning electron microscopic observations with sperm penetration tests carried out on cervical mucus under the influence of low-dose continuous progestogen (Norgestrienone) is presented. The results demonstrate that such type of contraceptive is involved in drastic alterations of mid-cycle cervical mucus at the macromolecular level. The meshwork which constitutes the infrastructure of the cervical secretion appears to be greatly tightened as a result of the treatment, thus giving the woof a general appearance typical of cervical mucus in the late luteal phase. The immobilizing effect of such modified mucus on spermatozoa is demonstrated and the duration of effectiveness after the administration of a last pill on the morning of day 13 is determined.

PIP: The antifertility and obstructive effects toward spermatozoa of a continuous low-dose progestogen contraceptive are examined in this study. Scanning electron microscopy (SEM) observations were correlated with sperm penetration tests carried out on cervical mucus. 11 healthy women aged 19 to 36 who were using no oral contraceptives were studied for 2 consecutive cycles. During the 2nd cycle, the women took a single, daily low-dose progestogen pill (350 ug of Norgestrienone) from the 1st till the 13th day. Blood samples were collected for determination of plasma estrogen levels, which were found to be normal during the control cycle. The progestogen was found to dramatically alter midcycle cervical mucus at the macromolecular level. The meshwork constituting the infrastructure of cervical secretion appeared to be greatly tightened by the treatment, giving the woof a general appearance typical of cervical mucus in the late luteal phase. The mucus framework revealed a tangle of micelles, and sperms leaving the seminal pool in the vagina were faced with such a succession of exhausting physical obstacles that they were unable to penetrate the uterine cavity. The SEM data shows that rendering the midcycle cervical mucus hostile interferes with sperm transport and this probably accounts for the effectiveness of the continuous low-dose progestogen therapy.

A study of interaction of a low-dose combination oral contraceptive with anti-tubercular drugs.

Low-dose combination contraceptive (containing norethisterone acetate 1 mg and ethinyl estradiol 30 micrograms) was administered to women receiving concurrent therapy with either Rifampicin or "triple" antitubercular treatment consisting of paraaminosalicylic acid (PAS), isonicotinic acid hydrazide (INH) and streptomycin. Plasma levels of norethisterone (NET) and ethinyl estradiol (EE), PAS and INH were measured and the area under curve (AUC) was calculated for NET and EE. Rifampicin treatment (9 women) caused a statistically significant reduction of the plasma NET levels as well as the AUC of NET. In this group of women, though a trend for reduction in EE levels was observed in individual subjects, it was not statistically significant. Out of 7 regularly menstruating women on Rifampicin therapy, 2 showed a premenstrual rise of plasma progesterone (P) levels (> 4 ng/ml) suggesting an ovulatory cycle and 3 experienced menstrual irregularities. In contrast, plasma levels of NET and EE as well as their AUCs were not altered in 8 women receiving "triple" antitubercular therapy. Only one woman out of 8, had menstrual irregularity and all women had P levels in the anovulatory range. Furthermore, oral contraceptive treatment did not alter the plasma levels of PAS and INH.

Intravaginal contraception with the synthetic progestin, R2010.

Four women used polysiloxane vaginal rings of core design containing 50 mg of norgestrienone (17 alpha-ethynyl-17 beta-hydroxy-estra-4,9,11,trien-3-one). The treatment was given in three-week cycles, leaving one treatment-free week between the cycles. The patterns of bleeding were registered and plasma norgestrienone (R2010), estradiol, progesterone, and gonadotropins were determined. Altogether twelve cycles were studied. The patterns of bleeding were unsatisfactory; only one subject had regular bleedings, and two of these were preceded by a luteal phase. The mean plasma concentration of norgestrienone (R2010) produced by the rings was 0.9 ng/ml. Ovulation was observed in 25% of cycles studied. Some follicular activity was present in every subject as judged by estradiol peaks. Excluding LH peaks in subjects who ovulated, mild pituitary suppression was achieved by this treatment. The only side-effect complained of was acne in one subject. The ring was regarded as easy to use.

PIP: The clinical performance as well as effects on gonadal and pituitary functions were analyzed during use of a contraceptive vaginal ring (CVR) impregnated with R2010, a synthetic progestin. 4 regularly menstruating women aged 25-29 years, who were parous and married, volunteered, and treatment was given in 3-week periods, leaving 1 treatment-free week. The CVR was a polysiloxane ring of core design and contain 50 mg of norgestrienone. Bleeding patterns were registered along with plasma R2010, progesterone, estradiol, and gonadotropins (luteinizing and follicle stimulating hormones). A total of 12 cycles were studied for this investigation. Bleeding patterns were unsatisfactory. Only 1 of 4 subjects had regular, simulated menstrual bleedings; 2 of these bleedings were preceded by a luteal phase (according to hormone assays). Mean plasma concentration of the progestin produced by the rings was .9 ng/ml. In 25% of the cycles ovulation was observed; in addition, some follicular activity was present in all 4 subjects, based on measurement of estradiol peaks. Mild pituitary suppression was achieved in the 3 subjects who did not ovulate. An acne flare-up constituted the only reported side effect.

[Contraception with implanted gestagens]. / Kontraception ved implanterede gestagener.

PIP: 990 women, 18-35 years of age, underwent subcutaneous silastic implants of levonorgestrel (N = 492) and norgestrionone (N = 498). These patients were compared to 402 women who used the Copper-T 200 IUD. Control examinations were performed 1,3,6,9, and 12 months after contraceptive use began. There were 3 pregnancies in the levo-norgestrel group which occurred during the first 4 months of contraceptive use. There were 17 pregnancies in the norgestrionone group, which occurred toward the end of the contraceptive use period. Menstrual bleeding disorders were the most frequent reasons for discontinuing subcutaneous implant use and occurred more often among the levo-norgestrel patients (generally metrorrhagia and menorrhagia). There were 4 pregnancies among the IUD patients. The continuation rate for the levo-norgestrel group was 74.6%; for the norgestrionone users 79.9%; and for the IUD users 81.1%. Anemia and changes in blood pressure were not observed among the subcutaneous implant patients. IUD patients showed no weight gain, while the subcutaneous implant patients gained on an average 1 kg.^ieng

Contraception with long acting subdermal implants: I. An effective and acceptable modality in international clinical trials.

This paper presents results of a double blind, multi-centered and multi-national study of two progestin only subdermal implants used for contraception. A regimen of six capsules of levonorgestrel (Ng) used by 492 women had a net cumulative 12-month pregnancy rate of 0.6 percent and a continuation rate of 74.6 percent. 498 women used six capsules of norgestrienone (R2010) and experienced a net cumulative 12-month pregnancy rate of 3.5 percent and a continuation rate of 79.4 percent. The difference in the pregnancy rate was significant at P less than 0.01, while there was no significant difference in the continuation rates. Menstrual problems were the principal reason for termination of the levonorgestrel regimen, accounting for approximately half of all terminations. There were significantly fewer menstrual problems among users of the norgestrienone (R2010) capsules; the net cumulative 12-month termination rate for this reason was 4.3 percent. Results are compared with continuation and termination rates for acceptors of the Copper T 200 at the same clinics. The low pregnancy rate and reasonably high continuation rate of the norgestrel implants coupled with the fact that the expected effective lifetime of a set of capsules is of the order of 3-5 years appears to warrant further development of this contraceptive regimen.

Long acting contraceptive implants. An analysis of menstrual bleeding patterns.

The menstrual patterns of women using subdermal implants of levonorgestrel and norgestrienone included in a double-blind clinical trial was evaluated by the method developed by the International Committee on Contraception Research. Women using Copper T200 randomly selected in the same clinics were used as controls. Both implant regimens were associated with a high frequency of reduced bleeding and norgestrel patients had also a high proportion of increased and irregular bleeding. Termination of use was associated to increased bleeding but not so much to reduced bleeding.