Jørgen Starup

Regression of endometriosis following shorter treatment with, or lower dose of danazol: Comparison of pre‐ and post‐treatment laparoscopic findings in the Scandinavian multi‐center study

Abstract. One hundred and sixteen patients with laparosco‐pically confirmed primary or recurrent endometriosis were treated with danazol, either 600 mg daily for 4 months (group A, n = 76) or 600 mg daily for the first 2 months, followed by 400 mg daily for an additional 4 months (group B, n = 40). The only surgery performed before treatment was biopsies, resection of endometriomas 23 cm and/or adhe‐siolysis. The extent of endometriosis before and after treatment was established laparoscopically and recorded by means of a modified AFS record as mean additive diameter of implants (mean ADI) in millimeters. This provided a uniform and reproducible quantitative registration for each type and location of endometriotic implant.

Anti-cardiolipin antibodies (IgG and IgA) in women with recurrent fetal loss correlate to clinical and serological characteristics of SLE

Aim of study. We investigated to which degree IgG, IgA and IgM anti‐cardiolipin antibodies (aCL) are associated in recurrent abortion or late fetal death with other signs of autoimmune disease and in particular SLE.

Ovarian Morphology in Early and Late Human Pregnancy

Abstract. Representative ovarian biopsies were obtained from 30 pregnant women aged 15 to 40. Group I consisted of 6 women with pregnancies of a gestational age of 9 to 18 weeks, and group II consisted of 24 women with pregnancies of a gestational age of 36 to 42 weeks.

Amenorrhoea Following Oral Contraception

Investigation of 31 patients who developed amenorrhoea following the use of combined oral contraceptives for a period of 3 to 84 months revealed that 55% had a variable degree of oligomcnorrhoea prior to the treatment. It is therefore concluded that an antecedent menstrual dysfunction is a relative contra‐indication to treatment with combined oestrogen‐gestagen preparations, and that another form of contraception should be recommended in these cases.

Ovarian morphology and pituitary gonadotrophins in serum during and after long-term treatment with oral contraceptives.

Abstract. The aim of the present investigation was to directly correlate the development of ovarian follicles with the levels of FSH and LH in serum during long‐term treatment with oral contraceptives in order to discover to what extent follicular maturation beyond the stage of early primary follicles depends upon stimulation with pituitary gonadotropins.

STUDIES ON THE MODE OF ACTION OF CLOMIPHENE CITRATE

Abstract. In order to further investigate the mode of action of clomiphene citrate, 5 oophorectomized women in the age range 28 to 41 years were followed with weekly determinations of serum FSH and LH for 20 weeks after the operation. They received no treatment during the first 4 weeks but during the next 16 weeks they were given estradiol 2 mgx2 daily orally, and from the 12th to the 16th week in addition clomiphene citrate 50 mgx2 daily. The high level of FSH after the oophorectomy decreased gradually during the treatment with estradiol alone, but this effect was partly neutralized by clomiphene citrate, as we observed a significant increase in FSH within 1 week of initiating treatment with clomiphene citrate. On the other hand, we did not find any significant changes in FSH within 4 weeks after treatment with clomiphene citrate was discontinued. The high level of LH after oophorectomy did not show any significant changes during the whole treatment period. It is concluded that clomiphene citrate primarily stimulated FSH secretion, most probably by a competition with estradiol for the receptor sites in the hypothalamus or the pituitary. In addition, it is concluded that clomiphene citrate has a prolonged effect, probably because of a tight binding to the receptor sites.

The Effect of Gestagen and Oestrogen Treatment on the Development of Ovarian Follicles: Laboratory Observations

The effect of megestrol acetate mestranol and a combination of these on the development of ovarian follicles in 16 patients was studied. After 1 cycle of treatment with megestrol acetate 6 patients had macroscopically normal ovaries; follicular development seemed normal and there were 3 fresh corpora lutea. Mestranol alone for 1 cycle in 3 women also showed macroscopically normal ovaries with normal follicles and 1 fresh corpus luteum. 8 patients were treated with megestrol acetate and mestranol. There were no fresh corpora lutea in any cycles. After treatment with the combined hormones for 3 cycles (1 patient) and 6 cycles (1 patient) there were no visible follicles and the ovaries were smooth and inactive. Follicular development had stopped at the secondary follicle stage and the tunica albuginea was definitely thickened. These changes are likely to be reversible. The few women who develop secondary amenorrhea may have a marked follicular fibrosis which fails to regress upon cessation of therapy.

LAPAROTOMY OBSERVATIONS DURING ORAL CONTRACEPTION

Since 1962 106 patients (aged 22-43 years) using an oral contraceptive have undergone surgical sterilization. Observed temperature curves were biphasic before oral contraception was begun. Delpregnin (megestrol acetate 5 mg and mestranol .1 mg) was used. Therapy began on Days 5-12 of their cycles. Operations were done on Day 24. Tubal sterilization inspection and biopsy of ovaries and uterine curettage were performed. Urinary gonadotropins or pregnanediol were determined on the day prior to operation. None of the 35 who had started Delpregnin earlier than Day 8 of their cycles ovulated. Of 8 patients who started Delpregnin on Day 8 2 had ovulated. 7 of 9 who started on Day 9 and all who started oral contraception later had ovulated by Day 24. Some patients ovulated after having received only 1 of the 2 components of Delpregnin from Day 5 of their cycles or the 2 components sequentially. Urinary hormone assays from the day preceding the operation showed normal gonadotropins. Pregnanediol secretion was below 1 mg in 24 hours. In 22 patients taking Delpregnin exogenous administration of pregnant mares serum gonadotropin (PMSG) alone did not induce ovulation or corpus luteum formation. Exogenous administration of human chorionic gonadotropin (HCG) alone induced corpus luteum formation during the 1st and 2nd but not the 3rd cycle. PMSG and HCG combined could induce a normal gonadotropin response as late as the 20th cycle. It is concluded that the Delpregnin contraceptive effect of preventing ovulation was due to suppression of pituitary gonadotropins.

The Mechanism in Inhibiton of Ovulation in Oral Contraception

11 previous investigations we have found an unfailing inhibition of the ovulation during cyclical treatment with Delpregnin (5 mg of megestrol acetateS0.1 mg of mestranol), as shown by laparotomy on day 24 in the cycle. During long-term treatment a significant, but gradual and rather slow decrease in the excretion of total gonadotrophins was found. This led to the assumption that the inhibition of ovulation was caused by a central effect on the h y p o t h a l a m ~ p i t ~ ~ system. We therefore tried to counteract this effect and to induce ovulation during cyclical treatment with Delpregnin by exogenous a d ~ t r a t i o ~ f PMS done, HCG alone, or a combination of both. The standard dose was: 1,500 IU of PMS on days 8, 10, and 12 and 4,500 IU of HCG on days 13, 14, and 15. The response of the ovaries was assessed at laparotomy on day 24 by direct inspection and by histological examination of biopsies of the ovaries. Stimulation with PMS alone did not induce ovulation, even during the first month. With HCG alone it was only possible to induce ovulation in the first two months, but with PMSSHCG we found that ovulation occurred even after 20 months of treatment. The conclusion was that the mechanism in the inhibition of ovulation is essentially an inhibition of the pituitary gonadotrophins. Probably LH is inhibited before FSH, but prolonged treatment causes an inhibition of both LH and FSH. In the present investigation we determined the daily excretion of total pituitary gonadotrophins (biologically) and LH (immunologically) in 4 normally menstruat~g women aged 20 to 28 in a control cycle followed by two cycles in which they received cyclicd treatment with Delpregnin. Furthermore, we determined the excretion of pregnaiie~ol

A Comparison Between the Efficacy and Side-Effects of Oral Contraception Using Closely Related Combined and Sequential Preparations

The reliability and side effects of a combined contraceptive containing megestrol acetate and mestranol were compared with a sequential contraceptive containing the same compounds. There were 4 method failures in the sequential group and none in the combined group. In women using the combined preparation breakthrough bleeding was observed more often along with a decrease in flow and duration of bleeding and an increase in weight. Headache was a more common complaint with the sequentials. There was no relationship between the type of contraceptive and the occurrence of nausea fibroids or cervical erosions.