Nils Crona

Women with polycystic ovary syndrome wedge resected in 1956 to 1965: a long-term follow-up focusing on natural history and circulating hormones.

OBJECTIVE To determine if the hormonal imbalance in women with polycystic ovary syndrome (PCOS) continues into and after menopause and to analyze factors constituting an increased risk for developing metabolic disorders. DESIGN The study was a transectional retrospective cohort follow-up of patients with PCOS. SETTING The women with PCOS were recruited from hospital clinics, and referents were randomized from a population study of women. PARTICIPANTS Thirty-three women ages 40 to 59 years with ovarian histopathology typical of PCOS at wedge resection 22 to 31 years previously; 132 age-matched referents were analyzed. MAIN OUTCOME MEASURES Clinical data were collected via a questionnaire supplemented with an interview in connection to a clinical examination that also included fasting venous sampling. RESULTS Infertility, hirsutism, and oligomenorrhea were more common among the subjects with PCOS, but there was a considerable spontaneous restitution of cyclic regularity with time. Women with PCOS were more often hysterectomized and entered menopause later compared with referents. The hormone data show a typical profile for PCOS. Compared with referents women with PCOS showed marked increase in prevalence of central obesity, higher basal serum insulin concentrations, and a higher prevalence of diabetes mellitus and hypertension. CONCLUSION Perimenopausal women with PCOS have an increased morbidity in hypertension and diabetes mellitus that adds to the classic symptoms, such as anovulation, hirsutism, and infertility.

Progestogens and lipid metabolism

Most of the available knowledge concerning hormonal influences on lipid metabolism is based on measurements of serum concentrations of various lipid and lipoprotein fractions. The existence of a progestogenic influence is inferred from either clinical factors or measurements of this kind. However, between these two sets of endpoint data there are wide and disturbing gaps in our knowledge where we have only fragmentary information. A hormone’s net effect may consequently appear identical when assessed by reference to these endpoints, while the metabolic pathways leading to them could well be different. It is accordingly possible to devise a hormonal replacement regimen that will exert minimum effects on serum lipids and lipoproteins in plasma, but the combination used may not necessarily be the best one as far as metabolic action is concerned. It is, for instance, quite clear that while pregnancy is associated with vast changes in lipid metabolism, it appears to have little impact on the incidence of myocardial infarction. Both exogenously administered and endogenously produced hormones influence lipid metabolism in several ways. For instance, general well-being, physical and psychic activity as well as dietary habits, use of alcohol and tobacco may be influenced, and these are known in turn to affect lipid metabolism. Exogenously administered hormones could also influence the endogenous hormonal milieu, especially in women with an intact ovarian-hypothalamic axis. These effects can be summarised as indirect hormonal effects on lipid metabolism (Table I). Administration of a hormone implies administration of a .compound having certain defined physiological effects which are mediated by receptors. Since receptors occur in several target organs, including the brain and the liver, it is quite clear that the hormone will also have direct effects which are partly receptor-mediated. Moreover, when a compound is administered generally, it influences metabolism

Human granulosa cell tumor: Stimulation of steroidogenesis by gonadotropins in vitro

A 59-year-old previously oophorectomized woman underwent surgery for a recurrent malignant granulosa cell tumor. Specimens and dispersed cells from the tumor tissue were incubated for 2 hr and cultured for 48 hr, respectively, with and without gonadotropins. Steroids and cyclic AMP (cAMP) concentrations were measured in the incubation and culture media. Incubated specimens from the tumor tissue released measurable amounts of cAMP, progesterone, and estradiol into the medium. Human follicle-stimulating hormone (FSH) 1 microgram/ml significantly stimulated the formation of cAMP and both steroids. Human luteinizing hormone (LH) 1 microgram/ml stimulated cAMP and progesterone but not estradiol release. Human chorionic gonadotropin (hCG) 10 micrograms/ml stimulated cAMP and progesterone formation in tumor tissue but was totally devoid of effect on estradiol release. In the tissue culture experiments progesterone and estradiol were formed in considerable amounts, with a higher capacity for progesterone than for estradiol. Progesterone formation was stimulated by FSH and hCG, while estradiol release was stimulated only by hCG. The addition of testosterone significantly enhanced estradiol formation in both incubation and culture experiments. It is concluded that the steroidogenesis of this granulosa cell tumor is sensitive to gonadotropins.

A comparison of the effects of ethinyl estradiol and estradiol valerate on serum and lipoprotein lipids

Serum lipids and lipoproteins were assessed after treatment with 2 mg of oestradiol valerate (E2V) and 10 micrograms of ethinyl oestreadiol (EE) in a group of 24 oophorectomised women in a study with an open cross-over design. E2V in this oral dose was quite inert in its effect on lipoprotein lipids. Ten micrograms of EE is a dose which in most women is sufficient to alleviate post-menopausal vasomotor symptoms. However, this low dose of EE increased serum triglycerides as a result of increased levels in the ultracentrifugally isolated lipoprotein fractions. Increased levels of serum and lipoprotein triglycerides are considered cardiovascular risk factors in women.

Does Position and Size of Corpus Luteum Have Any Effect on Nausea of Pregnancy

It is a puzzling fact that emesis might occur in one pregnancy, whereas other pregnancies in the same woman could be either free or again associated with nausea. Pregnancy‐associated hormones are believed to cause nausea, possibly through effects mediated via the liver. in 43 women who applied for a legal abortion in early pregnancy the occurrence of nausea was recorded and the position and size of the corpus luteums were measured by means of ultrasound. It was found that emesis was associated with corpus luteum located predominantly on the right side, while the non‐emetic pregnancy often had a left‐sided corpus luteum. It is suggested that the venous drainage, which differs between the right and the left side, may be responsible for the fact that the same woman can either suffer from or be free from nausea during pregnancy. Ovarian vein insufficiency, being more common in multigravidity, may also explain why nausea is more common in multigravidae.

Effect of oestriol, oestradiol valerate and ethinyloestradiol on serum proteins in oestrogen-deficient women

The effect of oestriol (3 mg for 3 mth), oestradiol valerate (2 mg for 3 mth) and ethinyloestradiol (0.025 mg for 21 days) on sex hormone binding globulin (SHBG), transcortin, ceruloplasmin and pregnancy-associated macro-globulin (PAG) was analysed in oestrogen-deficient women. The doses of oestrogens were therapeutically effective for the treatment of oestrogen-deficiency symptoms. Treatment with 0.025 mg ethinyloestradiol induced a 281% increase in PAG, a 119% increase in SHBG, a 74% increase in transcortin and a 74% increase in ceruloplasmin levels. Administration of 2 mg oestradiol valerate resulted in a 40% increase in SHBG, a small increase in transcortin and ceruloplasmin, whereas PAG levels remained unaffected. None of the parameters tested were affected by oestriol treatment. PAG was clearly the most sensitive parameter for ethinyloestradiol while SHBG was the most sensitive parameter for oestradiol valerate. These results show no relationship between clinical efficacy and effect of plasma protein synthesis, and demonstrate that one has to be very careful when comparing potency estimates for different oestrogens and different parameters.

Does Progestogen Reduction in Oral Contraception Parallel Reduced Lipid Metabolic Effects

Abstract. Twelve young fertile women participated in a cross‐over design study whose purpose was to evaluate the effect on lipid metabolism induced by two sequential contraceptive preparations. Sequilarum (50 μg of ethinylestradiol + levonorgestrel where the levonorgestrel dose is varied from 50 μg during the first 11 days up to 125 μg during the last 10 days of the cycle) was compared with Ova‐none (50 μg of ethinylestradiol for 22 days with the addition of 2.5 mg lynestrenol during the last 15 days of the cycle).

THE INFLUENCE OF HORMONAL REPLACEMENT THERAPY ON LIPID AND LIPOPROTEIN METABOLISM

Abstract. The widespread use of exogenous sex steroids for contraception, treatment of climacteric deficiency symptoms, etc., has led to the development of new compounds and combinations. Before new combinations of exogenous sex steroids or new steroidal compounds are introduced in clinical practice, evaluation of possible adverse metabolic effects should be mandatory.

High-dose depot-medroxyprogesterone acetate—Effects on the fatty acid composition of serum lecithin and cholesterol ester

Twenty-one women were treated with high doses of depot-medroxyprogesterone acetate (1000 mg/week im) for 6 months as part of the treatment of endometrial carcinoma. The relative fatty acid composition of serum lecithin and cholesterol ester were analyzed. In previous studies low doses of medroxyprogesterone acetate (MPA), in contrast to progestins of the 19-nor-testosterone series, have been shown not to affect the fatty acid composition of serum lecithin and cholesterol ester. However, the high doses of MPA used in this study increased linoleic acid and decreased arachidonic and di-homogammalinolenic acids in serum lecithin. The ability of a steroid to induce this shift has been ascribed to its androgenicity. MPA is considered to have weak, if any, such properties. The findings of this study emphasize the necessity to delineate effects on metabolism of different doses and administrative routes of any particular steroid.

Apolipoprotein A1 levels in oophorectomized women treated with Org OD 14, oestradiol valerate and a placebo

Org OD 14 is a synthetic steroid which in animal bioassays displays oestrogenic as well as very weak androgenic-anabolic properties. Earlier studies have shown that it alleviates oestrogen-deficiency symptoms and retards osteoporosis. OD 14 can be administered continuously with little effect on the endometrium. The aim of this study was to evaluate the effect of OD 14 on apolipoprotein A1 (Apo-A1), the major protein constituent of the high-density lipoprotein (HDL) fraction, as compared with that of oestradiol valerate (E2V) and a placebo. Twenty-two women, who had been oophorectomized when undergoing surgical treatment for stage IB or IIA cervical carcinoma, were given OD 14 2.5 mg/day, a placebo, and E2V 2 mg/day for a period of 6 wk in each case using a double-blind, cross-over method. Serum Apo-A1 was determined by electro-immunoassay after each treatment period. There was a marked decrease in Apo-A1 after OD 14 as compared with the levels seen after the placebo and E2V. This decrease is interpreted as evidence of a strong androgenic influence by OD 14. In epidemiological studies low levels of Apo-A1 have been associated with a higher incidence of atherosclerosis and cardiovascular disease. Long-term treatment with OD 14 might therefore be hazardous in this respect.