[Very early medical abortion, a termination of pregnancy before ultrasound evidence: something to aim for in the Netherlands?] / Zwangerschapsafbreking voordat de zwangerschap echoscopisch zichtbaar is.

OBJECTIVE: A very early medical abortion (VEMA) is an abortion early in pregnancy before the pregnancy is visible on an ultrasound. This treatment has been offered in several countries for many years. Our objective was to investigate whether VEMA is also desirable and can be carried out safely, in the Netherlands. DESIGN: Descriptive study. METHOD: From August 2019 to February 2020 VEMA was offered to women who met the inclusion criteria. A fixed protocol for diagnostic examinations and follow up was used. Ultrasounds and serial human chorionic gonadotrophin assays were used to ensure safety and effectiveness. Satisfaction survey was conducted among clients and employees. The costs of different treatments, including VEMA, were compared. RESULTS: During the study period 693 women received an abortion treatment in our clinic. 69 women met the inclusion criteria for VEMA. Three of them were referred to the local hospital because of an (suspected) ectopic pregnancy. No ectopic pregnancy was missed later in the process. VEMA was effective in 64 women. Two women needed a second treatment. Eight women did not appear for follow-up without an extra reminder. Women and healthcare providers were very satisfied with the offer of VEMA. VEMA was more expensive than other forms of treatment. CONCLUSION: Our study showed that very early medical abortion is safe and achievable in the Netherlands and highly appreciated. When introducing this treatment, a strict protocol is necessary. We advise to offer this treatment to women who prefer a very early abortion.

Continuous low dose estradiol released from a vaginal ring versus estriol vaginal cream for urogenital atrophy.

OBJECTIVES: To determine if the efficacy of continuous low dose estradiol released from a vaginal ring is equivalent to estriol vaginal cream regarding improvement of the patient's subjective feeling of vaginal dryness and to determine if there is a preference for either of the two study treatments. METHODS: Open-label randomized parallel group trial with active control with a blind evaluation of vaginal cytology and with a cross-over (change-over) phase for preference comparison. One hundred and sixty five postmenopausal women with symptoms of vaginal dryness and signs of vaginal atrophy were randomized to an estradiol ring (Estring) or estriol cream (Synapause). The duration of each treatment period was 12 weeks. RESULTS: Both study treatments were equally effective regarding the ability to alleviate the symptom feeling of vaginal dryness and the signs of vaginal atrophy. Both treatments were efficient in restoring the vaginal mucosa, recorded as higher maturation values and as decreased vaginal pH. Estring was superior to estriol cream regarding preference of treatment. Both treatments were equivalent for the occurrence of adverse events, including bleeding. CONCLUSION: data from this change-over study confirm efficacy and safety of both the vaginal ring and cream in the treatment of postmenopausal women with urogenital atrophy symptoms and signs. The patients had a strong preference for the vaginal ring.

Influence of two hormone replacement therapy regimens, oral oestradiol valerate and cyproterone acetate versus transdermal oestradiol and oral dydrogesterone, on lipid metabolism.

OBJECTIVE: To compare the influence on lipid metabolism of two discontinuous, sequentially combined hormone replacement therapy (HRT) regimens. STUDY DESIGN: In an open, randomized study in 60 women, a full lipid profile including Lp(a) and liver function tests were assessed in a fasting state at the end of treatment cycles 6 and 12. Group A was treated with 2 mg oestradiol valerate (days 1-21) sequentially combined with 1 mg cyproterone acetate (days 12-21); group B was treated with a patch releasing 50 micrograms oestradiol daily, twice a week (3 weeks), sequentially combined with 20 mg dydrogesterone (days 12-21) orally. Statistical analysis by two-sided one-way analysis of covariance (covariable is baseline) for adjusted means of lipid parameters and rank transformation analysis for lipoprotein(a) (Lp(a)) was performed. RESULTS: Both groups were statistically comparable. The trial was completed by 45 subjects. Protocol violations occurred in 3 cases. Twelve subjects, equally divided between the groups, dropped out mainly because of adverse reactions. Both treatments were equally effective in the treatment of climacteric complaints. Liver function tests during the treatment period were normal in both groups. In group A, a statistically significant (P < 0.05) decrease versus baseline was observed in the serum levels (adjusted means) of the following parameters after 6 and 12 treatment cycles: total cholesterol (TC)-5% and -7%, respectively; low-density lipoprotein cholesterol (LDL-C) -13% and -14%, respectively; low-density lipoprotein cholesterol/high-density lipoprotein cholesterol ratio (LDL-C/HDL-C ratio) -16% and -18%, respectively. Triglycerides (TG) levels were significantly increased by 28% and nearly significantly (P = 0.07) by 25% after 6 and 12 treatment cycles, respectively. In group B, all lipid parameters (with the exception of apolipoprotein A-II which was significantly decreased after 12 treatment cycles) remained unchanged during therapy. Statistically significant differences for all aforementioned variables were found between the groups after 6 and 12 treatment cycles, respectively, with the exception of TC after 12 treatment cycles. After 6 treatment cycles, Lp(a) was decreased significantly (-18%) in group A as compared with baseline; after 12 months the decrease was -17% without reaching statistical significance. In group B, Lp(a) showed a slight but not statistically significant tendency to increase by 2% and 12% after 6 and 12 treatment cycles, respectively. Differences between both groups did not reach the level of significance. CONCLUSION: In this randomized, comparative study, a sequentially combined oral HRT regimen consisting of oestradiol valerate (2 mg daily on days 1-21) and cyproterone acetate (1 mg daily on days 12-21), induced a lipid pattern and probably also a change in Lp(a) levels, which is generally viewed to be more beneficial with regard to the prevention of cardiovascular disease than the lipid pattern induced by a sequentially combined regimen of transdermal 17 beta-oestradiol (50 micrograms twice weekly during three weeks) and oral dydrogesterone (20 mg daily on days 12-21).

The effects of continuous combined transdermal oestrogen-progestogen treatment on bleeding patterns and the endometrium in postmenopausal women.

Fifty postmenopausal women requiring hormone replacement therapy for the treatment of climacteric symptoms were recruited in six centers. All patients received a new combined norethisterone acetate (NETA)/oestradiol (E2)-TTS, (Estragest TTS, Ciba-Geigy Ltd), delivering 0.25 mg NETA and 50 micrograms E2 per day, continuously for 12 calendar months. Bleeding occurred in 38 (76%) of the 50 patients at any time during the 1 year treatment. The percentage of patients without bleeding increased gradually each month, from 24% in the second month to a relatively stable level of approximately 80% in month 7 and thereafter. Twenty-seven patients (54%) did not complete the whole trial period; 15 of which discontinued the treatment within the first few months due to irregular bleeding. In patients who remained in the trial, a clear decrease in the frequency and intensity of the bleeding was observed with time. Bleeding was mostly light or consisted of spotting only. None of the post-trial biopsies showed proliferation or hyperplasia of the endometrium. The treatment resulted in a substantial decrease of climacteric symptoms (Kupperman index) within 4 months and was well tolerated. It was concluded that the continuous NETA/E2-TTS treatment is an effective and safe alternative for the treatment of climacteric symptoms in selected patients.