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Dan Apter

Publications and source records attributed to Dan Apter.

16 recordsLinked to original sources
PubMed2006

Enrolment of 22,000 adolescent women to cancer registry follow-up for long-term human papillomavirus vaccine efficacy: guarding against guessing.

Human papillomaviruses (HPVs, most notably types 16 and 18) cause cervical carcinoma, the second most common cancer among women. Vaccination of adolescents against HPV16/18 might prevent large proportion of cervical and other anogenital cancers. However, because of ethical reasons this cannot be proven by clinical studies. To determine the long-term vaccine efficacy (VE) of HPV16/18 virus-like-particle (VLP) vaccine against cervical carcinoma in situ (CIS+) and invasive cervical carcinoma, the following three population-based cohorts of adolescent women have been enrolled: (1) women vaccinated with the HPV vaccine; (2) women vaccinated with hepatitis A control vaccine; and (3) unvaccinated control women. These cohorts will be passively followed for cumulative incidence of CIS+ endpoints by population-based cancer registry. Overall 24,046 16- to 17-year-old adolescent women from 18 cities in Finland were invited between May 2004 and June 2005 to participate in a phase III trial with bivalent HPV16/18 VLP vaccine. A total of 58,996 18- to 19-year-old women were invited in May 2005 to participate as unvaccinated controls. Women who reported their willingness to participate in an HPV vaccination trial had they been 1-2 years younger were eligible. Cumulative incidence (CI) of CIS+ in our cohorts over 15 years is approximately 0.45%. VE of 70% against CIS+ with 80% power requires 3357-3189 HPV16/18 vaccine recipients, 3357-3189 other vaccine recipients, and 6714-9567 unvaccinated controls. We have now enrolled 2404 HPV16/18 vaccine recipients, 2404 hepatitis A-vaccine recipients, and 5130 unvaccinated controls. This enrolment in addition to our earlier enrolment in another phase III trial guarantees enough power so that by 2020 we can ultimately provide data on the efficacy of HPV16/18 vaccination against CIS+.

Adolescent↗
PubMed2006

[Not Available].

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Journal Article↗
PubMed2005

Contraceptive efficacy, compliance and beyond: factors related to satisfaction with once-weekly transdermal compared with oral contraception.

OBJECTIVE: To investigate contraceptive efficacy, compliance and user's satisfaction with transdermal versus oral contraception (OC). STUDY DESIGN: Randomized, open-label, parallel-group trial conducted at 65 centers in Europe and South Africa. One thousand four hundred and eighty-nine women received a contraceptive patch (n = 846) or an OC (n = 643) for 6 or 13 cycles. RESULTS: Overall/method-failure Pearl Indices were 0.88/0.66 with the patch and 0.56/0.28 with the OC (p = n.s.). Compliance was higher at all age groups with the patch compared to the OC. Significantly more users were very satisfied with the contraceptive patch than with the OC. The percentage of patch users being very satisfied increased with age whereas it did not in the OC group. Likewise, improvements of premenstrual symptoms as well as emotional and physical well-being increased with age in the patch-group in contrast to the OC group. Ratings of satisfaction with the study medication correlated weakly with emotional (r = 0.33) and physical well-being (r = 0.39) as well as premenstrual symptoms (r = 0.30; p < 0.001). CONCLUSION: Contraceptive efficacy of the patch is comparable to OC, but compliance is consistently better at all age groups. Higher satisfaction with the patch at increasing age may be attributed to improvements in emotional and physical well-being as well as reduction of premenstrual symptoms.

Administration, Cutaneous↗
PubMed2005

A multicenter phase IIb study of a novel combination of intramuscular androgen (testosterone decanoate) and oral progestogen (etonogestrel) for male hormonal contraception.

The effect of a novel combination of oral etonogestrel (ENG) and im testosterone decanoate (TD) on suppression of gonadotropins and spermatogenesis as a potential lead for male contraception was investigated. Healthy male volunteers were randomized into two groups receiving 300 microg ENG daily and 400 mg TD every 4 (n = 55) or 6 (n = 57) wk for 48 wk. At wk 48, all men except one in the 6-wk group suppressed sperm concentration to less than 1 million/ml. Faster suppression occurred in the 4-wk group. Gonadotropins were suppressed in both groups and most consistently in the 4-wk group. During treatment, trough testosterone levels increased into the normal range in the 4-wk group but remained just below normal in the 6-wk group. All peak levels were within the normal range. After treatment cessation, recovery of sperm counts and gonadotropins to normal levels occurred in both groups. Minor effects on weight and cholesterol were noted. Fourteen subjects withdrew because of an adverse event with those possibly related to the study medication reported more frequently in the 6-wk group (nine vs. one). In conclusion, the combination of 300 microg ENG with 400 mg TD every 4 wk was superior in terms of efficacy, hormone profiles, and safety. This represents a promising approach to male hormonal contraception.

Administration, Oral↗
PubMed2005

Clinical performance and menstrual bleeding patterns with three dosage combinations of a Nestorone progestogen/ethinyl estradiol contraceptive vaginal ring used on a bleeding-signaled regimen.

OBJECTIVE: We examined the clinical performance of contraceptive vaginal rings (rings) delivering Nestorone (NES) progestin and ethinyl estradiol (EE). Ring removal times were signaled by menstrual events. Bleeding patterns, adverse events, patterns of use and continuation rates were the principal parameters evaluated. METHODS: In a two-stage 6-month trial, subjects were randomized to use rings releasing 50 microg/day of NES and either 10 (50/10) or 20 (50/20) microg/day of EE. Subjects were to keep rings continuously in situ until menstrual bleeding or prolonged spotting-signaled removal. Reinsertion was to occur 96 h later. After the randomized stage, an open-label 6-month trial of rings releasing 150 microg/day of NES and 15 microg/day of EE (150/15) began with the same menstrually signaled regimen. RESULTS: Two-hundred forty-six subjects participated in the trial. Six-month pregnancy rates ranged by ring dose from 1.3 to 3.9 per 100. For each ring dose combination, 6-month continuation rates were above 80 per 100. Bleeding and spotting (B+S) days in women with the 50 microg/day NES rings were similar in number to those experienced by cycling women not using contraception. Nevertheless, in the initial 90 days, fewer B+S days were reported by subjects with the 50/20 ring than by subjects with the 50/10 ring (p < .05). Throughout the trial, subjects using the 150/15 ring reported significantly fewer B+S episodes than did subjects with either 50 microg/day NES ring. CONCLUSION: Combined contraceptive rings used with a bleeding-signaled regimen led to few terminations attributed to bleeding problems and to acceptable continuation rates. The 150/15 ring appeared to induce fewer bleeding problems than did the lower-dose NES combination rings, but no important difference in 6-month continuation rates among the three doses was noted.

Adult↗
PubMed2005

Serum Nestorone and ethinyl estradiol levels, and ovulation inhibition in women using three different dosage combinations of a Nestorone progestogen-ethinyl estradiol contraceptive vaginal ring on a bleeding-signaled regimen.

OBJECTIVES: This trial tested the hypothesis that menstrually signaled use of contraceptive vaginal rings ("rings") releasing low-dose combinations of Nestorone (NES) and ethinyl estradiol (EE) would reliably suppress luteal activity and ovulation, and prevent unintended pregnancy, while controlling the incidence of menstrual bleeding episodes and bleeding days. METHODS: Nestorone/ethinyl estradiol rings releasing 50/10, 50/20 and 150/15 mug/day were studied through 6 months. A ring was to be used continuously, until its removal was signaled by menstrual bleeding. Reinsertion was required 96 h after removal. Serum for NES, EE and progesterone were collected and assayed, and vaginal ultrasound scans were performed in three 5-week periods to examine luteal activity, follicular growth, ovulation and their correlates. In 10 subjects using the 150/15 ring, six samples were drawn in the 24-h period after ring removal to examine serum levels of NES and EE. RESULTS: One hundred sixty subjects at three doses provided blood samples. Median serum concentrations of NES and EE demonstrated dose ratios slightly below the nominal dose ratios expected. Serum NES concentrations declined 19-22% from weeks 3 to 25. Changes in EE levels depended on dose. Nestorone levels fell 81% by 24 h after ring removal and EE levels fell by 50%. Luteal activity was completely suppressed in 94-95% of cycles and in 90% of subjects. Three pregnancies occurred in subjects participating in this serum sampling study. CONCLUSION: Satisfactory serum levels of NES and EE, and a high level of ovulation suppression were achieved. Irregular ring use, however, permitted pregnancies to occur.

Contraceptive Agents, Female↗
PubMed2003

[Preventive vaccines against papillomavirus and cervix cancer will soon enter clinical practice].

A vaccine may protect against cancers caused by high-risk human papillomaviruses (HPVs). Sexually transmitted high-risk HPV types are almost always found in cervical cancer. Incidents of HPV type 16 and cervical cancer has more than doubled after the 1980's in Finland. HPV L1 capsid protein can be produced in the yeast, after which it assembles into virus-like-particles (VLP) and can be readily used for vaccine production. HPV VLP vaccine is well tolerated and induces ten-fold higher serum antibody levels as compared to natural infection. HPV16 VLP vaccine has shown to be 91% protective effect against HPV16 infections in the first phase III study. Neutralizing HPV antibodies, induced by HPV VLP vaccination, effectively reduce the viral load even though total elimination of the virus may not be needed. It is not known for how long the vaccine induced protection will last. Recruitment of adolescents into population-based phase III vaccination studies should be large to allow reliable cancer registry based evaluation of protective effect against grave dysplasia and cervical cancer.

Capsid Proteins↗
PubMed2003

Criteria for selective screening for Chlamydia trachomatis.

BACKGROUND: On the basis of studies in ethnically diverse populations, it appears that the best strategy for prevention of infections is screening of all women aged 25 years or younger. GOAL: The goal was to determine screening criteria in an ethnically and socioeconomically homogenous population with low prevalence of genital chlamydia infection. STUDY DESIGN: Women (N = 1198) attending two family planning clinics were screened for and surveyed for risk factors. Data were analyzed with multivariate logistic regression. RESULTS: The overall prevalence of infection was 3.5%. Risk markers for the infection included marital status, number of sex partners, and age. Screening women aged 25 years or younger would have identified 28% of all chlamydial infections, while screening all women aged 30 years or younger would have identified 83% of infections. CONCLUSION: Because of its feasibility, age appears to still be the best screening criterion. However, extension of the screening to include women up to 30 years of age should be considered.

Adolescent↗
PubMed2003

The role of leptin in female adolescence.

Leptin, the ob gene product, is related to the onset of puberty in animal models, but its role in human puberty is still rather undefined. In prepubertal girls and boys, leptin concentrations increase slowly with age and body-fat mass. In boys, this increase is interrupted in early puberty, when testosterone and lean body mass increase. In girls, leptin, along with the body-fat mass, continue to increase during puberty. Plasma leptin concentrations are significantly correlated with fat mass at all Tanner stages in males and females. The diurnal variation of leptin concentrations seen in adults is apparent for all age groups with no significant changes in the pattern across puberty. Leptin is bound in blood by a high-affinity binding protein identical with the soluble leptin receptor (sOB-R). In the first year of life, the concentration of sOB-R is high, and then a continuous decline of sOB-R follows until midpuberty. The therapeutic response to leptin treatment in a child with leptin deficiency confirms the importance of leptin in the regulation of body weight in humans, and establishes an important role for this hormone in the regulation of appetite. Still no evidence is available that would indicate leptin is a primary signal that initiates the onset of human puberty. Instead, it may act in a permissive way as one of several metabolic factors to allow pubertal maturation to proceed and later reproduction to occur.

Adipose Tissue↗
PubMed2002

Low dose mifepristone and two regimens of levonorgestrel for emergency contraception: a WHO multicentre randomised trial.

BACKGROUND: A single 10 mg dose of mifepristone, and two 0.75 mg doses of levonorgestrel 12 h apart, are effective for emergency contraception. Because no studies had compared the efficacies of both compounds, or investigated a single dose of 1.5 mg levonorgestrel, we undertook this three-arm trial. METHODS: We did a randomised, double-blind trial in 15 family-planning clinics in 10 countries. We randomly assigned 4136 healthy women with regular menstrual cycles, who requested emergency contraception within 120 h of one unprotected coitus, to one of three regimens: 10 mg single-dose mifepristone; 1.5 mg single-dose levonorgestrel; or two doses of 0.75 mg levonorgestrel given 12 h apart. The primary outcome was unintended pregnancy; other outcomes were side-effects and timing of next menstruation. Analysis was by intention to treat, but we did exclude some patients from the final analyses. FINDINGS: Of 4071 women with known outcome, pregnancy rates were 1.5% (21/1359) in those given mifepristone, 1.5% (20/1356) in those assigned single-dose levonorgestrel, and 1.8% (24/1356) in women assigned two-dose levonorgestrel. These proportions did not differ significantly (p=0.83). The relative risk of pregnancy for single-dose levonorgestrel compared with two-dose levonorgestrel was 0.83 (95% CI 0.46-1.50), and that for levonorgestrel (the two regimens combined) compared with mifepristone, 1.05 (0.63-1.76). Side-effects were mild and did not differ greatly between groups, and most women menstruated within 2 days of the expected date. Women who took levonorgestrel had earlier menses than did those who took mifepristone. INTERPRETATION: The three regimens studied are very efficacious for emergency contraception and prevent a high proportion of pregnancies if taken within 5 days of unprotected coitus. Mifepristone and levonorgestrel do not differ in efficacy. A 1.5 mg single levonorgestrel dose can substitute two 0.75 mg doses 12 h apart.

Adult↗
PubMed2002

Oral contraceptive use before first birth and risk of breast cancer: a case control study.

BACKGROUND: The aim of this study was first, to investigate whether women starting oral contraceptive (OC) use at a young age and before first birth have an increased risk for breast cancer and second, to report difficulties encountered in studying long-term health impacts of medical technologies. METHODS: Breast cancers occurring up until 1997 among 37153 Helsinki students born between 1946 and 1960 were identified by record linkage from the Finnish Cancer Registry; for each cancer case, five age-matched random controls were picked from the same student population. Those who had used the Helsinki Student Health Service (HSHS) at least three times (150 cases and 316 controls) form the final study subjects. Data on OC use and background characteristics were collected from patient records, and data on live births were derived from the population register. Odds ratios (OR) were adjusted for number of births, smoking and sports activity. RESULTS: Compared to the few non-users, OC users had a higher risk of breast cancer: the adjusted OR was 2.1 (95% confidence interval 1.1-4.2). Among OC users, no statistically significant differences in risk of breast cancer were found in regard to starting age or first birth, but small numbers made confidence intervals wide. Even though we had chosen students to be our study group, the population turned out to be unsuitable to answer our research question: most women had started their OC use old (at the age of 20 or later) and there were very few unexposed (almost all had used OC and before their first birth). CONCLUSIONS: Because adoption of the modern pattern of OC use was not common among students, it is unlikely that the impact of early and extended OC use can be studied before 2010, when women born in the 1960s are 40 to 50 years old.

Journal Article↗
PubMed2002

Efficacy, cycle control, and user acceptability of a novel combined contraceptive vaginal ring.

OBJECTIVE: To assess the contraceptive efficacy, cycle control, tolerability, and user acceptability of a novel combined contraceptive vaginal ring for up to 13 cycles. METHODS: Healthy women requesting contraception were enrolled in this 1-year multicenter study. Each ring released 120 microg of etonogestrel and 15 microg of ethinylestradiol daily, and was used for 3 weeks followed by a 1-week ring-free period. RESULTS: A total of 2322 women started treatment and so formed the intent-to-treat population. Subjects were followed for 23,298 cycles, equivalent to 1786 woman-years. Compliance was good with 85.6% of cycles in full compliance with specified criteria. In the intent-to-treat population, 21 pregnancies occurred, giving a Pearl Index of 1.18 (95% confidence interval 0.73, 1.80). Eleven of the pregnancies were attributable to noncompliance; the Pearl Index for the per-protocol population was 0.77 (95% confidence interval 0.37, 1.40). The mean incidence of withdrawal bleeding was 98.5% in all cycles. Irregular bleeding occurred in 5.5% of all cycles, and in most women, early or late withdrawal bleeding was restricted to spotting. The ring was well tolerated with a low incidence of adverse events; only 2.5% of all discontinuations were device related. The ring was easy to insert and remove and did not interfere with intercourse. Eighty-five percent of women were satisfied with the ring, and 90% would recommend its use to others. CONCLUSION: The ring is an effective contraceptive with excellent cycle control that is convenient, well tolerated, and highly acceptable to users.

Adolescent↗
PubMed2002

Update on female pubertal development.

PURPOSE OF REVIEW: To elucidate recent findings regarding female puberty. The successful completion of puberty is a prerequisite for reproduction. Many later disorders of fertility and metabolism may develop during puberty. New more sensitive and specific assays provided us with possibilities for a better understanding of the process of puberty, and the discovery of new factors such as leptin evoked the hope of finding key regulators of the onset of puberty. RECENT FINDINGS: The secular trend towards earlier menarche appears now to have come to an end, but discussions about changes in the age of pubertal onset still continue. In a few detected cases of leptin mutations puberty has not occurred spontaneously. The intact secretion of leptin seems to be a necessary prerequisite for the onset of puberty. Apart from that, recent research has indicated that leptin levels mainly reflect body composition. Leptin as well as gonadotropins, steroids and growth hormone shows specific circadian patterns. The 24 h pattern of leptin is similar before and after puberty, but the 24 h pattern of the other hormones changes. The serum concentration of inhibin B increases in the years preceding puberty and in early puberty, whereas inhibin A increases in mid to late puberty. SUMMARY: The biological significance of the changing circadian patterns remains to be determined. Inhibin B serum concentrations together with follicle-stimulating hormone may indicate remaining potential ovarian activity during childhood in, for example, patients with Turner syndrome, but more information and other possible markers are needed.

Adolescent↗