A forgotten founding father of the Pill: Ferdinand Peeters, MD.

Ferdinand Peeters, a practising gynaecologist from Turnhout, near Antwerp (Belgium), had a pivotal role in the development of a practical and viable modality of oral contraception, striking the balance between efficacy and an acceptably low incidence and severity of side effects. While, with regard to the origin of oral contraception, names like those of Pincus, Rock, and Djerassi come immediately to the fore, the work of Peeters has to a large extent faded from public memory. Still, it was Peeters who proposed to Schering AG in Berlin that a combination of 4 mg norethisterone acetate and 0.05 mg ethinylestradiol be used for ovulation suppression. He convinced the scientific staff of Schering of the potential benefits of what, after clinical trials, would finally emerge as Anovlar.

Sexual functioning in women using levonorgestrel-releasing intrauterine systems as compared to copper intrauterine devices.

INTRODUCTION: There has been little research published on the impact of intrauterine contraceptive (IUC) methods on sexual functioning. AIMS: This study aimed: (i) to assess different aspects of sexual functioning, including the prevalence of sexual dysfunction in women using a levonorgestrel intrauterine system (LNG-IUS); (ii) to compare this prevalence with that among copper-releasing intrauterine device (Cu-IUD) users; and (iii) to identify the relationship between psychological variables and sexual functioning in women using one of the aforementioned IUCs. METHODS: In a multicenter cross-sectional study, 845 women with an IUC were invited to fill out a questionnaire. The latter was returned by 402 (48%) of them: 353 women were LNG-IUS users (88%) and 49 were Cu-IUD users (12%). The questions asked pertained to depression, well-being, marital relation quality, and sexual functioning. MAIN OUTCOME MEASURES: Sexual functioning was measured with the short sexual functioning scale. RESULTS: One-third of LNG-IUS users (33%) reported a sexual dysfunction. Of those, 20% reported an increased sexual desire, 25% a decreased sexual desire, 5% arousal problems, and 8% orgasm problems. Women using a LNG-IUS did not differ significantly in distribution, type, or prevalence (32.9% vs. 36.7%) of sexual dysfunction, nor in depressive symptoms (Beck Depression Inventory score; 4.7 vs. 3.9; P = 0.33), general well-being (WHO-5 well-being scale score; 16.8 vs. 17.7; P = 0.170), or partner relationship quality (Dyadic Adjustment Scale score; 107 vs. 108; P = 0.74) compared to Cu-IUD users. Overall, the perceived influence of IUCs on sexual functioning was in the lower range and did not differentiate LNG-IUS greatly from Cu-IUD-users. CONCLUSION: Women using a LNG-IUS do not differ from those wearing a Cu-IUD with regard to psychological and sexual functioning. The perceived impact of IUD use on sexuality should not be overestimated.

The Femilis LNG-IUS: contraceptive performance-an interim analysis.

OBJECTIVE: To provide an update on the experience with the Femilis levonorgestrel-releasing intrauterine system (LNG-IUS) used for up to five years by parous and nulliparous women, particularly with regard to its contraceptive performance. STUDY DESIGN: An interim, open, prospective non-comparative study of the Femilis LNG-IUS releasing 20 microg of levonorgestrel/day. RESULTS: Two-hundred and eighty insertions were carried out in women with a mean age of 35.7 years (range 17-48), 60% of whom were parous and 40% nulliparous. Twenty-four women with uterine pathology (e.g., fibroids, menorrhagia) were included in the study. The cumulative gross discontinuation life table rates were determined. The total observation period was 8,028 woman-months. The LNG-IUS was easy to insert in 95.7% of the cases, and no perforations occurred. No pregnancies were observed and only one expulsion took place (rate 0.4/100 women at five years). The cumulative total use-related discontinuation rate was 14.7/100 at five years. There were nine removals because of pain, six of which were in nulliparous women. Four women requested removal of the IUS for bleeding problems. Fourteen removals were done for 'other' medical reasons among which mood disturbances (five cases) were the most frequent, and 12 for non-medical reasons. Fifteen removals were requested for pregnancy wish. Twelve of these women became pregnant within one year and all had uneventful pregnancies. The Femilis LNG-IUS was equally well accepted by nulliparous as by parous women. Most women with heavy menstrual bleeding prior to insertion, whether associated with fibroids or not, reported much less bleeding, scanty bleeding or even no bleeding at all after insertion. CONCLUSION: This study suggests that the Femilis LNG-IUS, which releases 20 microg LNG/d, is a highly effective, well tolerated and well retained contraceptive both in parous and nulliparous women. The shorter crossarm of the LNG-IUS has simplified its insertion technique, which may contribute to its safety. This could promote use by non specialist providers and enhance the application of the method.

Efficacy of a single oral dose of 200 mg pramiconazole in vulvovaginal yeast infections: an exploratory phase IIa trial.

Pramiconazole (R126638) is a novel azole with potent antifungal activity against yeasts, dermatophytes and many other fungal species. The aim of this study was to evaluate the efficacy and tolerance of a single oral dose of 200 mg pramiconazole in acute and recurrent vulvovaginal yeast infections. Thirty-two patients (15 acute and 17 recurrent cases) were KOH microscopy- and culture-positive at inclusion. Clinical cure was 53% at one week and 66% at one month. Mycological eradication was obtained in 88% at one week, whereas at one month 75% of the patients were still culture-negative. Effects in both acute and recurrent cases appeared to be similar for mycological cure. The composite sign and symptom score (sum of scores for oedema, erythema, excoriation pruritus, burning and irritation) had a median value of 7.5 (range 2-17) at inclusion. At one week this value was reduced to 1.0 (range 0-8) and at one month a further reduction to 0 (range 0-11) was seen. p-values compared with baseline at both follow-up visits were <0.001. The drug was well tolerated and the reported adverse events were rare and minimal. In conclusion, the results of this trial indicate that pramiconazole possesses properties that warrant further clinical studies in a larger number of patients with acute and recurrent vulvo notvaginal yeast infection to confirm its efficacy and tolerability.

Pupils' over-reliance on linearity: a scholastic effect?

BACKGROUND: From upper elementary education on, children develop a tendency to over-use linearity. Particularly, it is found that many pupils assume that if a figure enlarges k times, the area enlarges k times too. However, most research was conducted with traditional, school-like word problems. AIMS: This study examines whether pupils also over-use linearity if non-linear problems are embedded in meaningful, authentic performance tasks instead of traditional, school-like word problems, and whether this experience influences later behaviour. SAMPLE: Ninety-three sixth graders from two primary schools in Flanders, Belgium. METHOD: Pupils received a pre-test with traditional word problems. Those who made a linear error on the non-linear area problem were subjected to individual interviews. They received one new non-linear problem, in the S-condition (again a traditional, scholastic word problem), D-condition (the same word problem with a drawing) or P-condition (a meaningful performance-based task). Shortly afterwards, pupils received a post-test, containing again a non-linear word problem. RESULTS: Most pupils from the S-condition displayed linear reasoning during the interview. Offering drawings (D-condition) had a positive effect, but presenting the problem as a performance task (P-condition) was more beneficial. Linear reasoning was nearly absent in the P-condition. Remarkably, at the post-test, most pupils from all three groups again applied linear strategies. CONCLUSIONS: Pupils' over-reliance on linearity seems partly elicited by the school-like word problem format of test items. Pupils perform much better if non-linear problems are offered as performance tasks. However, a single experience does not change performances on a comparable word problem test afterwards.

Intrauterine levonorgestrel delivered by a frameless system, combined with systemic estrogen: acceptability and endometrial safety after 3 years of use in peri- and postmenopausal women.

OBJECTIVE: To evaluate the acceptability and endometrial safety of a novel intrauterine drug delivery system, FibroPlant-levonorgestrel (LNG), combined with estrogen therapy (ET) in 150 peri- and postmenopausal women, followed-up for at least 3 years. DESIGN: This was a prospective, non-comparative study in peri- and postmenopausal women. In the majority of women, treatment with the FibroPlant-LNG intrauterine system (IUS), combined with ET, was initiated during the perimenopausal transitional phase to establish a smooth transition to menopause and suppress the endometrium to prevent endometrial proliferation and bleeding. A 3.5-cm long coaxial fibrous delivery system, delivering approximately 14 microg LNG/day, was used. The calculated duration of release of the system is at least 3 years. The majority of women received percutaneous 17beta-estradiol (Oestrogel), 1.5 mg daily on a continuous basis, which provides sufficient blood levels of estrogen in most women to suppress climacteric symptoms and protect against bone loss. OUTCOME MEASURES: To measure acceptability, women were asked, after they had the IUS in place for a minimum of 3 years, if they would like to continue the combined regimen and if they would accept renewal of the IUS. Endometrial safety was evaluated by transvaginal ultrasound examination and endometrial biopsy in a subset of 101 women prior to replacement of the IUS. RESULTS: Ninety-four insertions were done in perimenopausal and 56 in postmenopausal women aged between 33 and 78 years. Of the total group of 150 women, 132 women (88.0%) accepted replacement of the IUS and ten are waiting for replacement. This group includes nine women who will receive a second replacement. The number of women continuing the method is 142 (94.6%). Histological examinations conducted on endometrial biopsies from 101 postmenopausal women prior to replacement, after an average period of use of the regimen of 40 months (range 25-50 months), showed predominantly inactive endometrium characterized by pseudodecidual reaction of the endometrial stroma with endometrial atrophia, which is in keeping with the effects seen with a progestogenic compound. There were no specimens showing signs of proliferation. CONCLUSIONS: Results suggest that the frameless FibroPlant-LNG IUS is safe, well tolerated, well accepted and effective in suppressing the endometrium during ET. Intrauterine progestogen administration in postmenopausal women can be regarded as fundamentally advantageous compared with systemically applied progestogens, which may have potentially inherent ill side-effects, especially on the breast and cardiovascular system, as reported in the recent literature.

Ease of insertion, contraceptive efficacy and safety of new T-shaped levonorgestrel-releasing intrauterine systems.

OBJECTIVE: The objective of the study was to evaluate ease of insertion, contraceptive performance and safety, in parous and nulliparous women, of two new T-shaped levonorgestrel (LNG)-releasing intrauterine systems (LNG-IUS), Femilistrade mark (parous women) and Femilis Slim (nulliparous women), releasing 20 mug of LNG per day. An ancillary objective was to evaluate expulsion and user continuation. DESIGN AND METHODS: An open, prospective, noncomparative study (interim analysis). Two hundred thirty-five insertions were performed in fertile women seeking contraception. Of these, 143 (60.8%) parous women were fitted with Femilis and 92 (39.2%) nulliparous women were fitted with Femilis Slim. The LNG-IUS was inserted using a simplified push-in technique (without folding the cross-arms in the insertion tube). RESULTS: This paper is the first report with the Femilis LNG-IUS. The push-in technique of insertion was considered simple and safe. Insertion was reported "easy" in virtually all women (97.9%). Pain at insertion was absent in 24.7% and "mild" in 67.7% of women. With respect to pain, there were no statistical differences between the parous and nulliparous group. At the time of study analysis, the total number of women-months of use was 1769.7. Seventy-six women had the Femilis IUS in place for periods in excess of 1 year. The study was well followed up with lost to follow-up of only two women. No pregnancies were observed. There was one expulsion in the nulliparous and one in the parous group. Ten removals were performed for medical reasons (mainly bleeding and pain). One pelvic infection occurred in a nulliparous woman caused by Chlamydia trachomatis, which was resolved without removing the IUS. There were no other serious adverse events reported. Both Femilis and Femilis Slim were well tolerated, which resulted in a high continuation rate (94.04%). CONCLUSION: The Femilis LNG-IUS is an effective contraceptive and is easily inserted. The simple and safe insertion procedure could be an advantage for use by nonspecialist providers such as nurses, midwives, general practitioners, and for those not inserting intrauterine devices regularly. Femilis Slim could be an attractive long-term contraceptive option in young and adolescent women.

Continuous combined parenteral estrogen substitution and intrauterine progestogen delivery: the ideal HST combination?

OBJECTIVE: To evaluate ease of insertion, acceptability and endometrial safety of a novel, miniature intrauterine, T-shaped, levonorgestrel (LNG)-releasing intrauterine system (IUS), Femilis Slim LNG-IUS (Contrel Research, Belgium), combined with parenteral estrogen substitution therapy (EST) in postmenopausal women. DESIGN: A prospective, non-comparative, study in postmenopausal women. A 3.0 cm long and 2.0 mm wide coaxial fibrous delivery system, delivering approximately 20 microg/day of levonorgestrel (LNG) was used. The drug compartment is provided with crossarms fixed to the upper part of the drug delivery rod. The calculated duration of release of the system is at least 5 years. The majority of women received percutaneous 17beta estradiol (Oestrogel, Besins Int., Belgium), 1.5 mg daily on a continuous basis, which provides sufficient blood levels of estrogen in most women to suppress climacteric symptoms and protection against bone loss. PRIMARY OUTCOME MEASURES: ease of insertion, retention and side effects of the T-LNG Slim IUS. SECONDARY OUTCOME MEASURES: endometrial safety assessed by transvaginal ultrasound examination and by endometrial biopsy in a subset of women. RESULTS: One hundred and seventy insertions were performed in postmenopausal women with median age of age 56.6 (range 43.5-80.3). Insertion was easy in 161 (94.2%) and difficult in 9 (5.3%) women. Pain at insertion was rated as none in 57 women (33.5%), mild in 105 (61.7%), moderate in 7 (4.1%) and severe in 1 (0.5%) woman. The system was well retained in the uterus as no expulsions occurred. At the time of study analysis, the total number of women-months was 1797.5. Ninety-five women had the T-LNG-IUS in place for periods in excess of 1 year. The study was well followed-up with lost-to-follow-up rate (defined as no follow-up during 12 months) of zero at the time of study analysis. The number of women continuing the method was 160 (94.1%) including four women which were released from follow-up for various non-medical related reasons. The histological examinations conducted in 105 women showed predominantly inactive endometrium characterized by a pseudo-decidual reaction of the endometrial stroma with endometrial atrophy. The mean thickness (double-layer) of the endometrium was 3.3 mm (range 2-5 mm) which correlated well with the histology results. CONCLUSIONS: The results suggest that the small T-LNG-IUS is easy to insert in most postmenopausal women without anaesthesia and dilatation of the cervix. It is well tolerated, well accepted and effective in suppressing the endometrium during EST. The lack of expulsions of the device in this study is attributed to the optimal design characteristics of the IUS, the absence of uterine bleeding and absent or reduced contractility of the uterus. The study confirms earlier studies conducted with other LNG-releasing systems used for endometrial suppression during EST. The ease of insertion of the small LNG-IUS could be an important incentive to expand the use of the continuous combined regimen with local delivery of the progestogen. It could be a method of choice for endometrial suppression in women using EST with fundamental advantages to systemically applied progestogens which have been the subject of considerable debate as reported in the recent literature.

Development of a miniature, low-dose, frameless intrauterine levonorgestrel-releasing system for contraception and treatment: a review of initial clinical experience.

A low-dose levonorgestrel (LNG)-releasing intrauterine system (IUS) (FibroPlant) has been clinically developed since 1997 for endometrial suppression during hormone replacement therapy in peri- and postmenopausal women, for the treatment of menorrhagia in women with normal uteri or with uterine fibroids, for contraception, for the treatment of endometrial hyperplasia, and for alleviating primary and secondary dysmenorrhoea. Results of preliminary studies confirm the promising nature of this all-round drug delivery system. The low dose of LNG released accounts for the low hormonal side-effect rate and virtual absence of amenorrhoea in premenopausal women. The system has not yet been evaluated in tamoxifen users (to protect the endometrium), or in women with rectovaginal endometriosis. However, early indications suggest that the system will also be suitable for these indications. The frameless drug delivery support of this LNG-releasing IUS has been optimized to reduce the size of the foreign body and to maximize tolerance and continuation of use while simultaneously providing for the maximum duration of action.