Sten Jeppsson

A prospective long-term study in women from pre-menopause to post-menopause: changing profiles of gonadotrophins, oestrogens and androgens

To permit a more detailed hormonal characterization of the peri-menopause, 30 healthy women were examined at regular intervals over a 7-yr period, starting about 3 yr before the menopause. Even though most of the subjects periodically experienced climacteric symptoms, no hormonal supplementation was given. The serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), oestradiol and oestrone that were recorded essentially confirmed previous data obtained in cross-sectional studies. Within the 6-mth period around the menopause the serum levels of testosterone and androstenedione showed small but significant decreases of 18 and 16%, respectively. These decreases continued over the following years and amounted to about 30% after 3 yr. In contrast, neither the mean level of dehydroepiandrosterone (DHA) nor the DHA/DHA sulphate (DHAS) ratio changed significantly at the menopause, but DHA and DHAS concentrations declined slowly by about 20% over the 7-yr observation period. The mean level of DHAS showed an isolated increase during the last few months before the menopause. A similar, although not significant, increase was also seen in DHA and testosterone levels. After the first post-menopausal year a significant positive correlation was found between the levels of oestrone and androstenedione. This longitudinal study of individual women appeared to lend itself well to the investigation of even subtle hormonal fluctuations during the gradual transition to an established post-menopausal pattern.

CLINICAL TRIAL OF A NEW ORAL CONTRACEPTIVE PILL CONTAINING THE NATURAL OESTROGEN 17β‐OESTRADIOL

The natural oestrogen, 17β‐oestradiol, has been shown not to depress fibrinolysis and apparently has less influence on liver function and lipid metabolism than ethinyl oestradiol, the synthetic oestrogen in conventional‘combined’oral contraceptive tablets. A triple‐blind study was therefore made of 215 women during 2051 treatment cycles with oral contraceptives containing either (i) 4 mg of micronized 17‐oestradiol and 3 mg norethisterone (Netagen 403), (ii) 4 mg 17‐oestradiol plus 2 mg of oestriol and 3 mg norethisterone (Netagen 423) or (iii) 50 μg ethinyl oestradiol and 3 mg norethisterone (Netasyn). There were no pregnancies or thrombotic incidents. The numbers discontinuing treatment were about the same in the three groups, the main reasons being intermenstrual spotting in those on Netagen 423, amenorrhoea and weight gain in those on Netagen 403 and nausea and weight gain in those on Netasyn. The natural oestrogen showed promise as a new and safe component of the‘combined’pill.

Studies on the decreased gonadotropin response after administration of LH/FSH-releasing hormone during pregnancy and the puerperium

The responsiveness of the pituitary to luteinizing hormone releasing hormone (LRH) during pregnancy and the puerperium was studied in 15 women 18-32 years of age (3 puerperal, 6 pregnant, and 6 eumenorrheic). 25 mcg LRH dissolved in 1 ml sterile water was administered iv to all the subjects. Blood samples were obtained 10 minutes prior to, immediately prior to, and 10-120 minutes following injection. LH and follicle stimulating hormone (FSH) were determined by double antibody radioimmunoassay. No significant (p more than .05) FSH response was observed 8-10 days postdelivery. However, 2 weeks postpartum the mean FSH response was significant (p less than .01) but not that of LH (p more than .05). 4 weeks postpartum revealed a significant LH (p less than .05) and FSH (p less than .01) response. The response of pregnant women to LRH was insignificant (p more than .05). The LH response in eumenorrheic women was significant (p less than .01) as was that of FSH (p less than .01). It is concluded that, like pregnant women, puerperal women are less responsive to LRH than are aumenorrheic women.

Decreasing serum levels of sex hormone-binding globulin around the menopause and temporary relation to changing levels of ovarian steroids, as demonstrated in a longitudinal study

Abstract Blood samples collected longitudinally in 17 women over a period of 3 years, starting 1½ years before the menopause, were assessed for sex hormone-binding globulin (SHBG), 17β-estradiol (E 2 ), progesterone, and total testosterone. A slight (7.2%) decrease in mean SHBG from 4.25 ± 1.67 (standard deviation) mg/l to 3.95 ± 1.61 mg/1 was observed within the 6-month period encompassing the menopause. More specifically, the decrease appeared to commence at the menopause and to become clearly significant ( P = 0.01) some 2 to 6 months later. During the subsequent year, a further decrease to 3.64 ± 1.42 mg/l was observed, amounting to a total decrease in mean SHBG by 14.4% ( P 2 exhibited a marked decrease ( P P = 0.013) only with those of E 2 . It is concluded that decreasing E 2 levels appear to play a significant role in the downward modulation of SHBG levels commencing at the menopause.

Gonadal Steroids, Gonadotropins and Endometrial Histology in Postmenopausal Women with Malignant Ovarian Tumors

The concentrations of FSH, LH, 17‐β‐estradiol (E2), estrone (E1) and progesterone (P) were measured in peripheral and ovarian vein sera obtained at preoperative pelvic angiography from 5 postmenopausal women with malignant ovarian tumors. In 5 others the concentrations of E2, P and testosterone (T) were also measured in ascitic fluid collected at laparotomy.

Peripheral and Ovarian Venous Concentrations of Gonadal Steroids and CEA in Women with Ovarian Tumors

Abstract. In an effort to improve our knowledge of certain marker substances in human ovarian neoplastic diseases (both benign and malignant) 12 patients with ovarian tumors were studied. Ten of these were postmenopausal.

Effect of oral contraceptives on the liver in women with recurrent cholestasis (hepatosis) during previous pregnancies.

The hepatic effects of various sex steroids on 61 women who had had intrahepatic cholestasis of pregnancy and 19 control patients have been studied. Chlormadinone acetate and lynestrenol produced little or no increase of the serum enzyme activity. With the mestranol and a combined preparation of mestranol and chlormadinone acetate an increase of the serum enzyme activity was found, which, however, soon returned towards normal. No increase in the concentration of the serum bilirubin was found in any of the patients. The supposed risk of jaundice during the use of hormone contraceptives by such patients has been exaggerated.

Endometrial Histology and Circulating Levels of Medroxyprogesterone Acetate (Mpa), Estradiol, Fsh and Lh in Women with Mpa Induced Amenorrhoea Compared with Women with Secondary Amenorrhoea

Abstract. Circulating levels of medroxyprogesterone acetate (MPA), estradiol, progesterone and gonadotropins were determined in 11 women on long‐term treatment with depot‐MPA (Depo‐Provera® DMPA) 150 mg i.m. every 12th week as a contraceptive. the women had amenorrhoea due to the treatment. Endometrial biopsy was performed one week after injection and at the end of the 12 week period. Blood samples were taken on the same occasions. the findings were compared with those in 12 untreated women having secondary amenorrhoea. MPA was still detectable in serum and the end of the 12 week period. Endometrial biopsies showed gestagenic effects in the second as well as in the first biopsy. No MPA was detectable in the untreated women with amenorrhoea, and no gestagenic effects could be demonstrated in their biopsies. the estradiol levels in the DMPA group were in the range of the early follicular phase of a normal menstrual cycle and showed a significant rise at the end of the 12 week period. On the last sampling occasion the estradiol levels did not differ from those in the untreated women with secondary amenorrhoea. the levels of progesterone and gonadotropins were in the range of the early follicular phase in both groups. These observations support that DMPA 150 mg i.m. every 12th week is a depot‐preparation with prolonged effect, and inhibits ovulation and produces endometrial changes by means of biologically active serum concentrations throughout the 12 week period.

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.

Basal and LRH-stimulated secretion of FSH during early pregnancy

The gonadotropin response to 25 mug of LH/FSH releasing hormone (LRH) intravenously was investigated during the very first weeks of pregnancy. It was found progressively to decrease, and no response in FSH was found for more than 5 weeks. The basal levels of FSH showed the same decreasing tendency, and a few weeks after conception they were often close to the sensitivity limit of the assay. With this report we have continued our description of the changing pituitary responsiveness to LRH from conception to the puerperium. During later stages of pregnancy the plasma levels of FSH were markedly reduced, and the response was inhibited even after 500 mug of LRH intervenously. The return of the response during the puerperium showed a specific pattern with a dissociation of the response in FSH and LH. No such dissociation was found during the period of progressive inhibition during the very first weeks of pregnancy.