Rune Rolland

Endometrial epithelial cells in peritoneal fluid during the early follicular phase

Peritoneal fluid (PF) was obtained during the early follicular phase in 24 women at laparoscopy as part of infertility investigation. The cells present in PF were pelleted and cultured. Developing endometrial epithelial cell colonies were identified in 19 women (79%). Identification of these cell colonies was facilitated using the monoclonal antibody BW 495/36 as specific marker. The number of endometrial epithelial cell colonies showed a large variation (1 to 200 or more PF sample). No significant distinction in incidence and number of cell colonies was found between women with minimal (n = 11) and without endometriosis (n = 12). A significant correlation with number of cell colonies was found in women with infertility and no mechanical and male infertility factors. These data indicate that retrograde transport of viable endometrial cells during menstruation occurs in most women with patent tubes. Implications of the results for the relation between retrograde menstruation, endometriosis, and infertility are discussed.

Hormone replacement therapy may reduce high serum homocysteine in postmenopausal women

Abstract In a prospective study we investigated the possible changes in fasting serum total homocysteine concentrations during continuous micronized 17β‐oestradiol, 2 mg daily, in combination with cyclic dydrogesterone, 10 mg daily during the first 14 days of each 28 day cycle, in 21 healthy non‐hysterectomized postmenopausal women. During the first six cycles mean serum homocysteine decreased by 10·9% (P= 0·013), after which no further significant changes were found during the 2 years of treatment. A 16·9% decrease (P= 0·017; n= 8) was found in women with high homocysteine concentrations, while in women with low homocysteine concentrations (n= 13) no significant changes were observed. The observed decrease in high homocysteine concentrations in postmenopausal women may in part contribute to the decreased risk of developing cardiovascular disease during hormone replacement therapy.

Ovarian stimulation and granulosa-cell tumour

Abstract Ovarian stimulation in the treatment of infertility is far from physiological because patients and their ovaries are exposed to high concentrations of gonadotropins. Many studies have focused on the two most common side-effects of ovarian stimulation—ie, hyperstimulation and multiple pregnancy. We describe 12 patients in whom granulosa-cell tumour was discovered after ovarian stimulation treatment with clomiphene citrate and/or gonadotropins. Although we cannot prove a causal link between the tumour and the medication, investigations in animals have shown a relation between gonadotropin exposition and the development of granulosa-cell tumours. The possible relation of ovarian stimulation and granulosa-cell tumours in human beings has not been published before. We postulate three explanations for this finding; first, the granulosa-cell tumour is present in the ovary, waiting for a hormonal trigger; second, increased follicle stimulating hormone concentrations are oncogenic to granulosa cell; and third, the onset of the granulosa-cell tumour during ovarian stimulation is coincidental. We recommend that ovarian stimulation is done only if there is a valid indication after proper assessment of the ovaries, and that women who have had ovarian stimulation are followed for longer than at present.

Diathermy loop excision in the management of cervical intraepithelial neoplasia : diagnosis and treatment in one procedure

OBJECTIVEnDiathermy loop excision was performed as a new diagnostic-treatment in patients with cervical cytologic diagnoses consistent with an epithelial abnormality.nnnSTUDY DESIGNnA total of 424 patients with cervical cytologic diagnoses consistent with an epithelial abnormality, but macroscopically or colposcopically not consistent with invasive carcinoma, were subjected to diathermy loop excision to diagnose and treat cervical lesions in one procedure.nnnRESULTSnThe diagnostic accuracy rate was 99%. In patients with histologically confirmed grade 3 cervical intraepithelial neoplasia, pretreatment cytologic diagnosis and subsequent histopathologic diagnosis corresponded in 73% of cases. In 91% of all patients the diathermy loop excision was sufficient for complete treatment. Cervical morphologic findings after treatment allowed adequate cytologic follow-up. There was no evidence that diathermy loop excision influenced fertility or pregnancy outcome.nnnCONCLUSIONnDiathermy loop excision is a reliable, well-tolerated, inexpensive, and efficient technique for the management of cervical intraepithelial neoplasia. This outpatient procedure is especially recommended in younger patients, because diathermy loop excision preserves the function of the cervix.

THE ROLE OF PROLACTIN IN THE RESTORATION OF OVARIAN FUNCTION DURING THE EARLY POST-PARTUM PERIOD IN THE HUMAN FEMALE

Serial plasma levels of prolactin, follicle‐stimulating hormone (FSH), luteinizing hormone (LH), 17β‐oestradiol (E) and progesterone (P) were determined by radioimmunoassay in ten healthy women during late pregnancy and the puerperium during inhibition of lactation by Bromergocryptine. This medication was continued until the occurrence of the first menstruation, at which point an endometrial biopsy was taken. Prolactin was very effectively suppressed by Bromergocryptine in all patients, as was lactation. FSH was nearly undetectable during late pregnancy and the first week post‐partum with an increase back to normal levels between day 7 and day 12. Thereafter FSH levels were within the normal cyclic range. Following clearance of human chorionic gonadotrophin (HCG) during the first 2 weeks post‐partum, LH was found within the normal cyclic range in all patients. From day 7 E increased in nine of ten patients to reach levels during the fourth week which are seen normally at the moment of the pre‐ovulatory E‐surge in cycling women. In eight of the ten cases this was concomitant with high levels of LH. The tenth patient showed a high E level at day 36. P was fully excreted within 7 days and remained low until approximately day 20. Thereafter an increase was demonstrated with levels as found during the luteal stage of the menstrual cycle in nine patients within 33 days and within 40 days in all ten patients. The endometrial biopsies showed clear signs of secretory activity. The probable action of prolactin on ovarian function is discussed. It is suggested that during the puerperium the ovaries are the more refractory part of the hypothalamic‐pituitary‐ovarian axis, due probably to an influence of prolactin on the ovarian steroid synthesis.

The effect of sequential three-monthly hormone replacement therapy on several cardiovascular risk estimators in postmenopausal women

OBJECTIVEnTo investigate the changes in plasma lipids and lipoproteins, low-density lipoprotein (LDL) oxidizability, and plasma homocysteine during postmenopausal sequential 3-monthly hormone replacement therapy.nnnDESIGNnOpen longitudinal prospective study.nnnSETTINGnGynecological outpatient department of a university hospital.nnnPATIENT(S)nThirty-nine healthy nonhysterectomized postmenopausal women.nnnINTERVENTION(S)nOral conjugated estrogen, 0.625 mg/d, combined with oral medrogestone 10 mg/d during the last 14 days of each 84-day treatment cycle. The treatment was given for four treatment cycles of 84 days (1 year).nnnMAIN OUTCOME MEASURE(S)nPlasma lipids and lipoproteins, LDL oxidizability, and plasma homocysteine.nnnRESULT(S)nAfter 1 year of treatment plasma concentrations of total cholesterol and LDL cholesterol were 3.5% and 8.7% lower, respectively. High density lipoprotein cholesterol, apolipoprotein A-I, and triglycerides were 6.5%, 9.0% and 16% higher, respectively. Apolipoprotein B concentration remained unchanged. The results on LDL oxidizability were inconsistent. Plasma homocysteine decreased with 12.3% during the first 6 months of treatment in women with higher homocysteine concentrations at baseline. These values returned to baseline levels during the second half year of treatment.nnnCONCLUSION(S)nThis sequential hormone regimen induced beneficial changes in the conventional lipid and lipoprotein risk estimators, whereas the observed changes in the other markers remained inconclusive and/or of minor importance.

A new approach to the inhibition of puerperal lactation.

Inhibition of lactation by the new peptide ergot alkaloid 2‐Br‐α‐ergocryptine (CB154) was studied in a double‐blind trial. Forty patients divided into four groups were treated during seven consecutive days with daily doses of either 2.5 mg., 5.0 mg., 7–5 mg. of CB154 or a placebo. In terms of milk secretion, engorgement and pain the CB154 therapy was significantly better than the placebo. Tolerance of CB154 was good and no drug‐related side effects were observed. In a further trial CB154 was tried in five patients with already established lactation and in 22 patients who had not responded to standard hormonal therapy. With one exception (suppression of lactation after four months of full breast‐feeding) excellent results were achieved.

Mammographic changes in postmenopausal women on hormonal replacement therapy

The purpose of this study was to investigate the extent of the effects of hormonal replacement therapy (HRT) on the mammographic breast pattern in postmenopausal women. In a hospital-based study mammographic examinations of 81 postmenopausal women were evaluated retrospectively, before and after 1–2 years of treatment with oestrogens or a combination of oestrogens and progestagens. Each individual mammographic film was examined separately, and the glandular tissue was classified according to a modified Wolfe classification. In a screening-centre-based study two consecutive mammograms, with a 2-year interval, of 645 women, of whom 70 were using some kind of hormone therapy, were evaluated retrospectively. In the hospital-based study 31% of patients treated with combination HRT showed an increase in fibroglandular tissue compared with only 8.7% in the group treated with oestrogens alone. The difference was statistically significant (p=0.046). In the screening-based study 14.3% of the women using hormonal therapy showed an increase, whereas in the non-users no increase was found (p=1.24×10−10). After beginning HRT many women (between 14 and 25% in our experience) can be expected to undergo a mammographically detectable increase in fibroglandular tissue. Radiologists should be aware of the aetiology of such changes, and can obtain information on HRT most conveniently by having the technologist routinely question each patient.

Beneficial effects on serum lipoproteins by 17β-oestradiol-dydrogesterone therapy in postmenopausal women; a prospective study

STUDY OBJECTIVEnTo study the possible changes of reproductive hormones, sex hormone binding globulin, serum lipids and lipoproteins, lipoprotein (a) included, coagulation and glucose in postmenopausal women treated with 17 beta-oestradiol and cyclic dydrogesterone for 14 days per 28 days treatment cycle.nnnDESIGNnOpen longitudinal prospective study.nnnDURATIONnTwelve 28 days treatment cycles.nnnSETTINGnGynaecological department of university hospital.nnnSUBJECTSn27 healthy postmenopausal women.nnnRESULTSnAfter treatment for six cycles serum concentrations of FSH and LH decreased significantly with 43.0% and 24.4%, respectively. Serum concentrations of 17 beta-oestradiol and oestrone increased significantly with 302% and 792%, respectively, and SHBG increased as well with 111% (P < 0.01). Serum total cholesterol decreased with 9.0% (P < 0.01). Serum VLDL-cholesterol did not change significantly. Serum LDL-cholesterol decreased with 16.3% (P < 0.01) and HDL-cholesterol increased with 8.0% (P < 0.01). This was accompanied with similar significant changes in the apolipoproteins: apolipoprotein A-I rose with 14.4% and apolipoprotein B decreased with 6.0%. Serum triglycerides and VLDL-triglycerides increased significantly with 14.4% and 17.9%, respectively. Lipoprotein (a) decreased with 17.5% (P < 0.01). These results more or less sustained at cycle 12 of treatment. Serum concentrations of antithrombin III and glucose did not change. Fibrinogen decreased slightly but significantly below the initial value.nnnCONCLUSIONSnThis combination replacement therapy gives beneficial changes in lipid-metabolism, indicating a reduced risk of developing coronary heart disease without unfavourably changing coagulation and glucose metabolism. The expected beneficial changes with oestradiol alone are not counteracted by the intermittent addition of dydrogesterone. Therefore this oestrogen/progestagen scheme can, indeed, be recommended for use in HRT.

A 2-year study on the beneficial effects of 17β-oestradiol-dydrogesterone therapy on serum lipoproteins and Lp(a) in postmenopausal women: no additional unfavourable effects of dydrogesterone

INTRODUCTIONnPostmenopausal hormone replacement therapy (HRT) has been described to reduce the risk of developing cardiovascular disease (CVD), which can be attributed at least in part to beneficial effects of oestrogens on serum lipoproteins. Little is known about a possible counteracting effect by the progestogen integrated in modern HRT regimens.nnnOBJECTIVEnTo study the possible changes in serum lipids, lipoproteins and apolipoproteins during HRT with special emphasis on the possible progestational effect.nnnSTUDY DESIGNnIn an open-label longitudinal non-comparative study 23 healthy non-hysterectomized postmenopausal women were treated with continuous micronized 17 beta-oestradiol, 2 mg daily, in combination with cyclic dydrogesterone, 10 mg daily, the first 14 days of each 28-day treatment cycle. The women were followed for up to 2 years.nnnRESULTSnAfter 2 years serum total cholesterol and low-density lipoprotein cholesterol had decreased by 9.0% and 18%, respectively (P < 0.01), while high-density lipoprotein cholesterol had increased by 13% (P < 0.01). The latter change was accompanied with similar increases in apolipoprotein A-I (+16%; P < 0.01) and A-II (+13%; P < 0.01), while apolipoprotein B remained unchanged. Serum very low-density lipoprotein (VLDL) cholesterol and VLDL-triglycerides increased by 28% and 21%, respectively, the latter reflecting the slight increase in serum triglycerides by 21%. These values, however, remained within the normal range. Serum lipoprotein(a) decreased by 16% (P < 0.01). All calculated atherogenic indices decreased (P < 0.01) during the study period. Serum lipids and (apo)lipoproteins did not change after withdrawal of dydrogesterone for 14 days during the combination therapy in the last cycle studied. Serum fibrinogen decreased by 8.4% (P < 0.01) in the first 12 cycles, after which it increased to 13% above baseline value (P < 0.01 vs. baseline). Antithrombin III did not change and serum glucose decreased by 5.7%.nnnCONCLUSIONSnThis HRT regimen induces (and also when given for a longer period) beneficial changes in the lipid profile, without affecting important indicators of thrombosis. Also, the glucose metabolism does not seem to be interfered with. Cyclic administration of dydrogesterone does not unfavourably affect serum lipids and (apo)lipoproteins when combined with 17 beta-oestradiol supplementation. Therefore, this combination hormone regimen can be recommended for use in HRT.