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Biomedical subjects

E Hirvonen

Publications and source records attributed to E Hirvonen.

At least 19 recordsLinked to original sources
PubMed1998

Effects on the hemostatic system and liver function in relation to Implanon and Norplant. A prospective randomized clinical trial.

In this prospective randomized clinical trial, two long-term contraceptive implants were studied with respect to hemostasis and liver function in 86 healthy young women. The two implants used were Implanon, containing the progestagen etonogestrel (the biologically active metabolite of desogestrel) and Norplant, the implant containing the progestagen levonorgestrel. The results of the trial showed that both implants had similar small effects on the hemostatic system that are not suggestive of a tendency towards thrombosis. The effect on liver function was characterized by increases in total bilirubin and gamma-glutamyl transferase and decreases in alanine aminotransferase and aspartate aminotransferase.

Adult↗
PubMed1997

Transdermal oestradiol gel in the treatment of the climacterium: a comparison with oral therapy.

OBJECTIVE: To compare two doses of a transdermal oestradiol gel (Divigel/Sandrena) plus oral sequential medroxyprogesterone acetate (MPA) with oral oestradiol valerate plus oral sequential MPA (Divina/Dilena). DESIGN: Two year, randomised, open-label, comparative study. SETTING: Menopausal outpatient clinic in Helsinki. SUBJECTS: Postmenopausal women with climacteric complaints or already using HRT. INTERVENTIONS: (1) One gram gel containing 1 mg oestradiol for 3 months plus 20 mg oral MPA during the last 14 days; (2) 2 g gel containing 2 mg oestradiol for 21 days plus 10 mg oral MPA during the last 14 days; (3) 2 mg oestradiol valerate tablets for 3 weeks plus 10 mg oral MPA during the last 10 days. In all groups, each treatment period was followed by a 7-day medication-free interval. MAIN OUTCOME MEASURES: Climacteric complaints, bleeding control, bone mineral density, biomarkers of bone metabolism, lipid profile, tolerability and safety. RESULTS: With each preparation, climacteric complaints were significantly reduced and good bleeding control was obtained. In addition, maintenance of bone mineral density as well as a reduction of bone turnover was achieved in all groups. Lipid parameters showed no unfavourable changes. Continuation rates were similar in all groups with overall 74% of patients completing the first year, whereas 94% of patients who elected to continue completed the second year. Tolerability of the gel was good: only 1.7% of patients discontinued treatment due to skin irritation. CONCLUSIONS: Transdermal oestradiol gel and oral oestradiol valerate tablets, used in combination with oral sequential MPA, are effective regimens of HRT in postmenopausal women. Transdermal oestradiol gel is an efficient, well-tolerated form of HRT.

Administration, Cutaneous↗
PubMed1997

Effects of transdermal oestrogen therapy in postmenopausal women: a comparative study of an oestradiol gel and an oestradiol delivering patch.

OBJECTIVE: To compare the efficacy, safety and tolerability of an oestradiol gel (1.0 mg of oestradiol daily, Divigel/Sandrena) with those of an oestradiol delivering patch (delivering 50 micrograms oestradiol/24 h, Estraderm TTS) in hormone replacement therapy of postmenopausal women. Dydrogesterone tablets (Terolut), 10 mg daily for the first 12 days of every month, were used as the progestogen component of the therapy. MAIN OUTCOME MEASURES: The effect of treatment on clinical symptoms and on endometrium, total body bone mineral density and lipid metabolism as well as the tolerability of the treatments with special emphasis on skin irritation and compliance were evaluated. DESIGN: An open, randomised, controlled, parallel-group trial of 12 months' duration. SETTING: The Medical Clinic of Kalevankatu, Helsinki, Finland. PARTICIPANTS: One hundred twenty postmenopausal women were treated with transdermal oestradiol combined with dydrogesterone. In addition, 25 women without HRT served as a reference group for the bone mineral density measurements. RESULTS: Both treatment regimens were equally effective in alleviating climacteric symptoms, preserving bone mineral density and were equally safe. A trend towards heavier bleeding was detected in patients treated with the oestradiol delivering patch. A statistically nonsignificant decrease of total cholesterol and triglyceride concentrations but no change in high-density lipoprotein cholesterol concentration was observed in both groups. The acceptability of the treatment was higher in the gel group (96.4%) than in the patch group (90.7%). Only two (3.3%) women using the oestradiol gel complained of skin irritation whereas 28 patients (46.7%, P < 0.001) using the oestradiol delivering patch reported this adverse effect. CONCLUSIONS: Both the oestradiol gel and the oestradiol delivering patch are equally effective in hormone replacement therapy but the gel preparation is less irritative to the skin.

Administration, Cutaneous↗
PubMed1997

Sexuality of young women surviving leukaemia.

This study was designed to assess the sexuality of young women surviving acute leukaemia in childhood or early adolescence. Thirty of 31 survivors were compared with 50 healthy age matched controls. Three methods were used: a self report questionnaire, a face to face interview conducted by a psychiatrist, and a projective psychological test. The age at initiation of dating and sexual activity, the frequency of sexual intercourse, and opinions on sexual behaviour were similar in the two groups. With regard to inner sexuality, however, the survivors differed significantly from the healthy controls. Their images of sexuality were more restrictive, and their attitudes, especially those concerning sexual pleasure, were more negative than those of the controls. Sexual identity among the survivors was less often feminine and more often infantile as compared with the controls. The findings obtained with the three methods of assessment were concordant.

Adult↗
PubMed1996

Progestins.

The history of progesterone and hormone replacement therapy goes back to 1934 when Butenandt obtained crystalline progesterone and Kaufmann started to treat ovariectomized women with both estrogens and progesterone (Table 1). Today synthetic perorally active 19-nortestosterone and 17-alpha-hydroxyprogesterone derivatives are used in addition to contraception and hormone replacement therapy in a variety of gynecological disorders. In hormone replacement therapy progestin is added only to prevent development of hyperplasia of the endometrium and its consequences. However, because progestins may cause both subjective and metabolic adverse effects minimum effective antiproliferative doses are recommended. The duration of the progestin phase cannot be shortened to less than 10 days whereas the frequency of administration apparently can be reduced without increased risk of hyperplasia. Development of new modes of administration may further help in reduction of the doses.

Contraceptives, Oral, Hormonal↗
PubMed1996

A randomized, double-blind, multicentre study comparing the clinical effects of two sequential estradiol-progestin combinations containing either desogestrel or norethisterone acetate in climacteric women with estrogen deficiency symptoms.

OBJECTIVES: The aim of this study was to compare a new estradiol-desogestrel (E2-DG) regimen with an E2-norethisterone acetate (NETA) combination (Trisekvens) regarding the treatment of menopausal complaints, bleeding pattern, histology of the endometrium and the occurrence of adverse experiences. METHODS: A total of 310 peri-/postmenopausal women with climacteric symptoms were randomly allocated to oral sequential treatment with either the E2-DG combination (1.5 mg E2 for 24 days with 0.15 mg DG for the last 12 days followed by 1 placebo tablet for 4 days) or with the E2-NETA combination (Trisekvens, 2 mg E2 for 22 days with 1 mg NETA for the last 10 days followed by 1 mg E2 for 6 days). Treatments were administered double-blind for 12 cycles of 28 days. RESULTS: One hundred and four women, 48 in the E2-DG group and 56 in the E2-NETA group, discontinued the study due to bleeding irregularities and various adverse effects. Both treatments reduced menopausal symptoms and complaints effectively and almost equally. The alleviation of perspirations and the improvement of general fitness were more apparent (P = 0.009) during cycle 1 with the E2-NETA treatment but were greater (P < 0.02) during the last 9/10-12 cycles of E2-DG treatment compared to E2-NETA. Regular withdrawal bleeding appeared in 93% and 90% of the women during treatment with E2-DG and E2-NETA, respectively. Intermenstrual bleeding occurred in 8% of women receiving E2-DG and in 13% of women treated with E2-NETA. The corresponding figures for intermenstrual bleeding-spotting were 21% and 22%. Secretory endometrium was detected in 65% and 54% of the samples taken at the end of treatment with E2-DG and E2-NETA, respectively. No hyperplasia or atypia was found. No serious adverse events related to treatment occurred. CONCLUSIONS: Both regimens alleviated effectively menopausal complaints and did not induce hyperplasia of endometrium. The minor differences recorded between the two regimens were probably due to the differences in their composition concerning the amount of estradiol and its distribution along the cycle, the amount and type of progestin and the length of estradiol/progestin combination phase.

Administration, Oral↗
PubMed1995

Oral contraceptive containing natural estradiol for premenopausal women.

An open multicenter trial was performed in six centers in Finland to study the efficacy, safety and acceptability of a new biphasic oral contraceptive pill containing natural estradiol and cyproterone acetate. The participants were 288 women with a mean age of 39.3 +/- 3.4 years (range 30-49) who were willing to use the new pill as their only contraceptive method. In total, 23% of the women were smokers. The cumulative experience was 2800 treatment cycles during the first year. The net 12-month continuation rate was 63%. One pregnancy occurred in a woman who lost 5 tablets in the second treatment cycle, which gives a 12-month cumulative pregnancy rate of 0.4%. Serum progesterone values, determined twice during the third treatment cycle, showed ovulation inhibition in 95% of women. There were no serious side effects. Intermenstrual bleeding was recorded by 35.5% and 24.5% of women at 3 and 12 months, respectively. The bleedings became scantier in most women and dysmenorrhoea disappeared. No changes were observed in total and high density lipoprotein cholesterol concentrations after 1 year. With the exception of intermenstrual spotting, the efficacy, safety and acceptability of the new pill was almost as good as that of the modern low dose oral contraceptives. This is the first pill containing natural estradiol that has gained clinical acceptance and which can also be prescribed for smokers over 35 years old until the climacteric.

Adult↗
PubMed1995

Can progestin be limited to every third month only in postmenopausal women taking estrogen?

We evaluated whether a progestin, added for 14 days every 3 months to estrogen replacement therapy, is capable of preventing the development of endometrial hyperplasia in postmenopausal women during a treatment period of 2 years. Postmenopausal women (263) in 10 hospitals and medical centers in Finland participated in this non-randomized prospective multicenter trial. The women received estradiol valerate 2 mg daily for 84 days and 20 mg of medroxyprogesterone acetate daily for days 71-84 followed by seven drug-free tablets. This regimen was repeated four times per year. The first year of treatment was completed by 227 (86%) women and the second year by 143 out of 146 women. The incidence of unscheduled and heavy bleedings was higher in women who were postmenopausal for less than 3 years. Endometrial biopsies demonstrated progestational response in 64% at 12 and 24 months, respectively. The 3 month regimen prevented development of endometrial hyperplasia but was not able to restore a hyperplastic endometrium to normal.

Adult↗
PubMed1995

Intracranial blood flow during laparoscopic hysterectomy.

AIM OF THE STUDY: To examine intracranial blood flow during major laparoscopic gynecologic operation and the effects of a deep Trendelenburg position and pneumoperitoneum on the flow. MATERIAL: Fifteen patients scheduled for laparoscopic hysterectomy. METHODS: Trans-cranial Doppler examination of blood flow velocity waveforms in the middle cerebral artery during operation. RESULTS: Trendelenburg position and pneumoperitoneum were followed by a decrease in cardiac output and an increase of central venous pressure and pulmonary capillary wedge pressure. No significant changes in the pulsatility index or maximal or mean blood flow velocities in the middle cerebral artery occurred during operations. A negative correlation between percentual changes in the pulsatility index and mean arterial pressure existed. CONCLUSIONS: Uncomplicated laparoscopic hysterectomy is not associated with harmful changes in intracranial circulation in spite of a Trendelenburg position, pneumoperitoneum and changes in the patient's extracranial hemodynamics.

Adult↗
PubMed1994

Metabolic impact of adding medroxyprogesterone acetate to conjugated estrogen therapy in postmenopausal women. The Menopause Study Group.

OBJECTIVE: To evaluate the impact of different dosages of medroxyprogesterone acetate (MPA) on metabolism and hemostasis in postmenopausal women treated with conjugated estrogens. METHODS: In this prospective, double-blind study, 525 women were randomized to five treatment groups at 26 sites in the United States and Europe. All participants received 0.625 mg conjugated estrogens daily for up to 13 cycles; four groups also received MPA, either 2.5 or 5.0 mg/day continuously or 5.0 or 10.0 mg/day for the last 14 days of each cycle. Effects on lipid and carbohydrate metabolism and coagulation were evaluated. RESULTS: Beneficial changes in plasma lipid levels occurred in all groups, but were greatest with conjugated estrogens alone (P < or = .05). Fasting glucose and insulin levels were significantly lower and the insulin response to glucose challenge was significantly blunted in all groups (P < or = .05). No major changes of clinical significance occurred in hemostatic levels. CONCLUSIONS: Metabolic levels were not affected adversely by the addition of MPA to conjugated estrogens, but some beneficial changes were greater with conjugated estrogens alone. Hemostatic levels were not affected.

Aged↗
PubMed1993

A novel oestradiol--desogestrel preparation for hormone replacement therapy: effects on hormones, lipids, bone, climacteric symptoms and endometrium.

Desogestrel is a strong progestogen with low androgenicity which has so far been used only in oral contraceptives. We studied the feasibility of administering desogestrel in combination with oestradiol as hormone replacement therapy (HRT). Thirty women received a sequential combination containing 1.5 mg micronised oestradiol (24 days) and 0.15 mg desogestrel (last 12 days of cycle) for 6 months. At that stage 6 of the women dropped out; the remaining 24 were studied for a total of 12 months. The treatment alleviated vasomotor symptoms effectively in all the women and induced regular withdrawal bleeding in 86% of them. Secretory changes were observed in the endometria of 16 of the 20 women with adequate endometrial samples assessed after 12 months of treatment. No signs of hyperplasia or atypia were found. Six months of treatment resulted in a decrease in the mean serum follicle-stimulating-hormone concentration from 66.2 (+/- 4.3, S.E.M.) to 23.3 (+/- 3.1) IU/l and a rise in the oestradiol and sex-hormone-binding globulin concentrations from 87.9 (+/- 13.7) to 233.1 (+/- 20.4) pmol/l and from 52.1 (+/- 4.6) to 70.2 (+/- 5.6) nmol/l, respectively. Testosterone levels decreased. There were significant reductions in serum total and low density lipoprotein (LDL) cholesterol and triglycerides. After 12 months of treatment high-density lipoprotein (HDL) cholesterol values did not differ significantly from the pretreatment levels. The HDL/LDL and HDL/total cholesterol ratios increased. The treatment reduced bone turnover as indicated by decreases in bone alkaline phosphatase and osteocalcin serum levels and by lowered urinary calcium/creatinine and hydroxyproline/creatinine ratios. An increase of about 2% in forearm bone mineral density was also observed. This new oestradiol-desogestrel preparation therefore appears to be a promising alternative form of HRT. It alleviates climacteric symptoms effectively, exhibits favourable effects on serum lipids and lipoproteins and prevents bone loss.

Bone Density↗
PubMed1990

Cardiovascular death among women under 40 years of age using low-estrogen oral contraceptives and intrauterine devices in Finland from 1975 to 1984.

From 1975 to 1984, there were 1,585,000 women-years of oral contraceptive use and 1,975,000 women-years of copper-bearing intrauterine device use in Finland. During this 10-year period, 20 women between 15 and 39 years of age died of pulmonary embolism, 41 of coronary heart disease, and 311 of intracranial hemorrhage. The diagnoses were confirmed in 89% at necropsy examination. The contraceptive method used by patients was determined in 84% by means of inquiry sent to family planning clinics. Among the 20 patients who died of pulmonary embolism, four died while taking the pill, which gives a relative risk of 1.2 (95% confidence limits, 0.37 to 3.62; p = 0.78). The corresponding values for death from myocardial infarction and intracranial hemorrhage were 0.19 (95% confidence limits, 0.05 to 0.70; p = 0.01) and 0.36 (95% confidence limits, 0.18 to 0.70; p = 0.03), respectively. None among the copper intrauterine device users under the age of 40 years died of pulmonary embolism during 1,383,000 women-years of intrauterine device use. The relative risk of death from intracranial hemorrhage among intrauterine device users was 1.18 (95% confidence limits, 0.70 to 1.99, p = 0.25).

Adolescent↗
PubMed1990

Urinary excretion of prostacyclin and thromboxane metabolites in climacteric women: effect of estrogen-progestin replacement therapy.

To study the role of vasodilatory prostacyclin and vasoconstrictory thromboxane A2 in climacteric vascular instabilities, overnight urine samples were collected from sixteen women suffering from hot flushes and sweating before, during and after the six months' cyclic estradiol-desogestrel therapy as well as from ten non-climacteric control women. The urine was assayed for 6-keto-PGF1a and 2,3-dinor-6-keto-PGF1a (metabolites of prostacyclin) as well as for thromboxane B2 and 2,3-dinor-thromboxane B2 (metabolites of thromboxane A2) by means of HPLC and radioimmunoassay. No difference was seen in baseline prostaroid output between the climacteric and non-climacteric study groups. Furthermore, no relation was observed between individual prostanoid excretion and severity of vasomotor symptoms before replacement therapy. The replacement therapy abolished or markedly alleviated hot flushes and sweating, but prostanoid output did not change. Our data imply that climacteric symptoms are not accompanied by changes in the production of prostacyclin and thromboxane A2.

6-Ketoprostaglandin F1 alpha↗
PubMed1990

Comparison of two hormone replacement regimens--influence on lipoproteins and bone mineral content.

Two hormone replacement therapy regimens were tested in a double-blind clinical trial involving 49 patients. In both cases the oestrogen component was 2 mg oestradiol valerate. This was administered for 21 days and sequentially combined for 10 days with either 0.5 mg norgestrel + (Cyclo-Progynova) or 1 mg cyproterone acetate (SH D 461 A). Each treatment cycle was followed by a 7-day tablet-free period. Both regimens proved to be equally effective in alleviating climacteric complaints. However, the low-density-lipoprotein cholesterol lowering effect of SH D 461 A was found to be superior to that of Cyclo-Progynova. There were no changes in bone mineral content during the one-year treatment period with either combination.

Androgen Antagonists↗
PubMed1990

Ovulation inhibitors containing cyproterone acetate or desogestrel in the treatment of hyperandrogenic symptoms.

An open, randomized, multicenter study was carried out to compare two oral contraceptives as regards their therapeutic efficacy in androgenization symptoms such as acne, seborrhea and hirsutism in women. The preparations used were the combination of 2 mg cyproterone acetate (CPA) with 0.035 mg ethinyl estradiol (EE) (Diane 35, Schering AG, Berlin-West) and 0.150 mg desogestrel (DG) with 0.03 mg ethinyl estradiol (Marvelon, Organon, Oss, The Netherlands). The duration of therapy was 9 months. The combination of CPA-EE was used by 83 patients for 658 cycles and the combination of DG-EE by 79 women for 618 cycles. No pregnancy occurred under either therapy. Both preparations are well tolerated. However, some side-effects, such as reduced libido, nervousness and breast tenderness, were observed more frequently (p less than 0.05) in the DG-EE group than among the users of the CPA-EE combination. The therapeutic outcome was better in the CPA-EE group, especially in cases of facial acne (p less than 0.05). Seborrheic symptoms also responded better to the CPA-EE therapy. The results show that the CPA-EE combination is superior to the DG-EE combination in the treatment of acne and seborrhoea.

Acne Vulgaris↗
PubMed1990

Evidence of similar increases in bone turnover during nafarelin and danazol use in women with endometriosis.

Medical 'oophorectomy' by GnRH agonist or danazol is an effective treatment for endometriosis. Since increased bone loss is a potential risk of hypoestrogenism, we compared the effect of nafarelin and danazol treatment on bone metabolism. Twelve patients with laparoscopically confirmed endometriosis received nafarelin (400 micrograms day intranasally) and six patients danazol (600 mg day orally) for 6 months. Both treatments had already led to hypoestrogenism (E2 less than 21.6 pg/ml) after 3 months. They both were accompanied by an approximately 50% rise in 24-h urinary hydroxyproline output, suggesting accelerated bone resorption at 6 months; yet urinary calcium output did not change significantly. Serum osteocalcin rose by 80-120% and bone alkaline phosphatase activity by 34-40%, suggesting stimulated bone formation at the same time. No detectable changes ensued in cortical bone mineral content in the distal radius or in serum levels of calcium, calcitonin, parathyroid hormone, or aminoterminal propeptide of type III collagen. Three months after treatment, hydroxyproline output, serum osteocalcin and bone alkaline phosphatase were still elevated in women taking nafarelin, whereas only serum osteocalcin was elevated in women taking danazol. Our data thus suggest that bone turnover was increased during nafarelin and danazol therapy and that this effect was reversible.

Alkaline Phosphatase↗
PubMed1989

Specific and sensitive quantitation of medroxyprogesterone acetate in human serum by gas chromatography-mass spectrometry.

A procedure for the quantitation of medroxyprogesterone acetate in serum using gas chromatography-quadrupole mass spectrometry is described. Medroxyprogesterone propionate, synthesized from medroxyprogesterone, was used as the internal standard. The serum samples were extracted on Bond Elut C18 cartridges, and the acetate and propionate were determined as their 3-enol heptafluorobutyrate esters by selected-ion monitoring technique. The linear range of the standard curve in serum was 0.5-30 ng/ml with a lower limit of quantitation of 0.5 ng/ml. The coefficient of variation of the method was 3.1% at 10 ng/ml and 5.5% at 1 ng/ml. The method is very rapid, and it has been applied for routine measurements of medroxyprogesterone acetate levels in human serum after oral administration of 10 or 20 mg.

Gas Chromatography-Mass Spectrometry↗