The impact of a quadrivalent human papillomavirus (types 6, 11, 16, 18) virus-like particle vaccine in European women aged 16 to 24.

BACKGROUND: Quadrivalent human papillomavirus (HPV types 6/11/16/18) L1 VLP vaccine is highly effective in preventing HPV 6/11/16/18-related cervical and external genital disease. Herein, we evaluated the impact of the quadrivalent HPV 6/11/16/18 L1 VLP vaccine on prevention of HPV-associated cervico-genital lesions in a broad population of sexually active European women. METHODS: Female subjects (N = 9265) aged 16-24 with four or fewer lifetime sexual partners were enrolled and randomized to quadrivalent HPV vaccine or placebo. Subjects underwent cervicovaginal sampling for HPV DNA detection. Papanicolaou testing and anti-HPV 6/11/16/18 serology testing was also performed. RESULTS: Vaccine efficacy against lesions representing immediate cervical cancer precursors (cervical intraepithelial neoplasia grade 2/3 or adenocarcinoma in situ) related to HPV 6/11/16/18 in the per-protocol population was 100.0%[95% confidence interval (95% CI), 89.8-100.0]. Efficacy against external genital lesions (vulvar or vaginal intraepithelial neoplasia, condyloma, vulvar or vaginal cancer) related to vaccine HPV types in the per-protocol European population was 99.0% (95% CI, 94.4-100.0). CONCLUSION: These data demonstrate that quadrivalent HPV 6/11/16/18 vaccination programs in 16- to 24-year-old European women can be beneficial. NCT0009252, NCT00092534, NCT00092495.

High sustained efficacy of a prophylactic quadrivalent human papillomavirus types 6/11/16/18 L1 virus-like particle vaccine through 5 years of follow-up.

Human papillomavirus (HPV) causes cervical, vulvar, and vaginal cancers, precancerous dysplasia, and genital warts. We report data for the longest efficacy evaluation to date of a prophylactic HPV vaccine. In total, 552 women (16-23 years) were enrolled in a randomised, placebo-controlled study of a quadrivalent HPV 6/11/16/18 L1 virus-like-particle vaccine with vaccination at months 0, 2, and 6. At regular intervals through 3 years, subjects underwent gynaecologic examination, cervicovaginal sampling for HPV DNA, serum anti-HPV testing, and Pap testing, with follow-up biopsy as indicated. A subset of 241 subjects underwent two further years of follow-up. At 5 years post enrollment, the combined incidence of HPV 6/11/16/18-related persistent infection or disease was reduced in vaccine-recipients by 96% (two cases vaccine versus 46 placebo). There were no cases of HPV 6/11/16/18-related precancerous cervical dysplasia or genital warts in vaccine recipients, and six cases in placebo recipients (efficacy = 100%; 95% CI:12-100%). Through 5 years, vaccine-induced anti-HPV geometric mean titres remained at or above those following natural infection. In conclusion, a prophylactic quadrivalent HPV vaccine was effective through 5 years for prevention of persistent infection and disease caused by HPV 6/11/16/18. This duration supports vaccination of adolescents and young adults, which is expected to greatly reduce the burden of cervical and genital cancers, precancerous dysplasia, and genital warts.

Comparison of the maternal experience and duration of labour in two upright delivery positions--a randomised controlled trial.

OBJECTIVE: To compare two upright delivery positions at the second stage of labour in healthy primiparous women with regard to duration of the second stage of labour and maternal experience. DESIGN: A randomised controlled trial. SETTING: A county hospital delivery ward. SAMPLE: Primiparous subjects (n=271) were randomly allocated to a kneeling (n=138) or a sitting (n=133) position during the second stage of labour. A postpartum questionnaire was answered by 264/271 women (97%) participating in the trial. METHODS: Primiparous subjects were randomised to a kneeling or sitting delivery position during second stage of labour. Analysis was performed on an intention-to-treat basis. MAIN OUTCOME MEASURE: Duration of the second stage of labour. RESULTS: A comparison of the duration of the second stage of labour (kneeling 48.5 minutes+/-27.6 SD, sitting 41 minutes+/-23.4 SD) revealed no significant difference between the groups. A sitting position during the second stage of labour was associated with a higher level of delivery pain (P<0.01), a more frequent perception of the second stage as being long (P=0.002), less comfort for giving birth (P=0.03) and more frequent feelings of vulnerability (P=0.05) and exposure (P=0.02). There were no significant differences in the frequency of sphincter ruptures although a sitting position was associated with a higher degree of postpartum perineal pain (P<0.001) (Table 3). CONCLUSIONS: Kneeling and sitting upright during the second stage of labour do not significantly differ from one another in duration of the second stage of labour. In healthy primiparous women, a kneeling position was associated with a more favourable maternal experience and less pain compared with a sitting position.

Transcatheter closure of post-infarction ventricular septal defect with the Amplatzer Septal Occluder device.

There is an 80-90% mortality rate within the first 2 months of the occurrence of a post-infarction ventricular septal defect (VSD) with medical treatment alone. The muscular VSD presents a technical problem for the surgeon. Surgical treatment was unsuccessful in two patients. They were treated successfully using the Amplatzer Septal Occluder, with improvement in their condition.

Evaluation of an STD-prevention program for Swedish university students.

The authors evaluated a sexually transmitted disease (STD)-prevention program that combined a mass media campaign with peer education. The program was designed to increase Swedish university students' knowledge about STDs, improve attitudes toward condom use, and tell students where to get an STD checkup. Preintervention and postintervention postal questionnaires wer used with an intervention group and two types of control groups. Responses ranged from 32% to 67% for the randomly selected students and from 93% to 99% for classroom and clinic participants. The intervention was noticed by a majority of the students (85-98%) and discussed by 43% to 57%; more women than men observed and discussed the campaign. Knowledge about STDs, where to turn for STD checkups, and the intention of having an STD checkup increased. Attitudes toward condom use were equally positive before and after the intervention. Although it was successful in attracting attention and leading to discussion of STD prevention, the campaign did not encourage students to have an STD checkup.

Radiography of spontaneous periodontitis in dogs.

The pattern and distribution of periodontitis were investigated in 162 randomly selected dogs available for necropsy in veterinary practice. There were 82 males and 80 females of 50 different breeds (150 dogs were pure-bred and 12 were mongrels, aged between 7 months and 14 yr. Presence of periodontitis was determined by assessment of alveolar bone loss on radiographs of the skulls and jaws. Periodontitis occurred frequently with increasing age, although the prevalence varied markedly among and within different breeds. Of the breeds most represented in the sample, periodontitis was most frequently seen in poodles and dachshunds but was rarely recognized in German shepherd dogs. Regardless of age, the vast majority of the dogs displayed either one or both of two different radiographic patterns of alveolar bone loss. One pattern was characterized by slight, horizontal alveolar bone loss involving interradicular and interdental areas. The other pattern was one of predominantly crater-like, or narrow, vertical bone defects which, when advanced, often extended around a single root or tooth to surround the root apices. The two types of patterns did not seem to be breed-dependent. The posterior maxillary and mandibular premolars and molars were the most frequently affected teeth. Alveolar bone loss was most severe in the maxilla, while corresponding bone loss in the mandible was more often related to increasing age.

Five-year longitudinal study on limited food consumption and development of osteoarthritis in coxofemoral joints of dogs.

OBJECTIVE: To examine the effects of limited food intake on frequency and severity of osteoarthritis in coxofemoral joints of labrador Retrievers. DESIGN: Dogs were paired according to gender and body weight, within each litter at 8 weeks of age. One dog of each pair was fed ad libitum. The limit-fed pairmate was fed 75% of the amount eaten the previous day by the ad libitum-fed counterpart. ANIMALS: 48 Labrador Retrievers. PROCEDURE: All dogs received the same diet. Radiographic evaluation of coxofemoral joints for frequency and severity of osteoarthritis were made when dogs were 4 and 6 months and 1, 2, 3, and 5 years old. RESULTS: Radiographic evaluation for osteoarthritis indicated greater frequency and more severity of osteoarthritis in the ad libitum-fed group of dogs. CLINICAL IMPLICATIONS: Analysis of data suggested that limit feeding of dogs over a 5-year period minimizes development of osteoarthritis in the coxofemoral joints.

Temporal relationship between Uniplant insertion and changes in cervical mucus.

This study was undertaken to determine the time required by a single implant containing nomegestrol acetate to affect cervical mucus production and sperm penetration in women. All subjects were investigated and, if necessary, treated for any kind of cervicitis or vaginitis prior to starting cervical mucus study. The subjects had not used hormonal contraception for at least three months prior to investigation. They were counseled to use condoms during this study and also to refrain from intercourse during the period of cervical mucus sampling. Follicular development and endometrial thickness were analyzed by transvaginal sonography. Cervical mucus examination, sperm penetration test, and transvaginal sonography were performed during the control cycle and during the first cycle of Uniplant use. Blood samples were taken for the measurement of estradiol, LH, and progesterone. Cervical mucus and sperm penetration tests were evaluated according to the World Health Organization (WHO) criteria. In the treated cycle, when cervical mucus reached a score of 8-10, Uniplant was inserted, independent of the day of the cycle. Cervical mucus was then collected at 0, 4, 8, 12, 24, 48, and 96 h later until a marked change in volume, consistency, ferning spinnbarkheit, and cellularity was observed. All samples were also used for sperm penetration test. Preovulatory estradiol and LH peak decreased significantly compared to pre-implant insertion. Progesterone levels were within the normal limit. Cervical mucus and sperm penetration tests were not affected by Uniplant in the first 12 h. Twenty-four hours after Uniplant insertion, cervical mucus and sperm penetration tests were affected in 70.6% of the women. Forty-eight hours after implant insertion, the women were affected. Follicular rupture occurred in the majority of the women 48 h after implant insertion. Based on these results, it is possible to conclude that Uniplant can affect estradiol and LH preovulatory peaks and disrupt the process of cervical mucus production and sperm penetration, but it was unable to prevent ovulation when inserted in the preovulatory phase.

PIP: In Brazil, physicians inserted one single capsule of the nomegestrol acetate contraceptive implant (Uniplant) subcutaneously in the gluteal region of 17 healthy female volunteers (mean age = 24.62 years) when their cervical mucus score was 8-10. They performed cervical mucus examination, sperm penetration test, and transvaginal sonography during the control cycle and during the first cycle of Uniplant use. They took blood samples to measure estradiol, luteinizing hormone (LH), and progesterone. Uniplant contained 55 mg of nomegestrol acetate. The researchers aimed to determine the time between Uniplant insertion and changes in cervical mucus and in the ability of sperm to exhibit forward motility in the cervical mucus. When Uniplant was inserted in the early follicular phase, the preovulatory peaks of estradiol and LH were significantly lower than preinsertion peaks (539.4 vs. 1087.1 pmol/l and 12 vs. 40.4 IU/l, respectively; p 0.01). The lower progesterone levels in the treatment cycle were not significantly different than preinsertion progesterone levels (46.6 vs. 53.8 nmol/l; p = 0.055). Ultrasonography and progesterone levels indicated that 16 of the 17 treatment cycles were ovulatory. Neither cervical mucus nor sperm penetration was affected in the first 12 hours postinsertion. By 24 hours postinsertion, 70.6% of the women exhibited significant changes in both cervical mucus and sperm penetration. At the end of 48 hours, all 17 women had these changes. These findings suggest that Uniplant inserted in the periovulatory phase affects cervical mucus production, sperm penetration, and preovulatory peaks of LH and estradiol but does not affect ovulation.

Increased use of condoms among female university students: a 5-year follow-up of sexual behavior.

OBJECTIVE: To ascertain any changes in sexual behavior and attitudes as an indication of the impact of intensified information activities aiming at decreasing the risk of spread of sexually transmitted diseases among university students. METHODS: In 1989 questionnaires were offered to 275 consecutive female students visiting the Student Health Center. Identical questionnaires were mailed to 200 randomly selected women registered at Uppsala University. The study was repeated in 1994. The study was carried out in Uppsala, a city in Sweden with 27,000 university students. RESULTS: At the Student Health Center 241 (88%) participated in the study in 1989 and 262 (95%) in 1994. Corresponding figures in the postal survey were 137 (69%) in 1989 and 151 (76%) in 1994. Compared with the findings in 1989, in 1994 the sexual behavior was unchanged in terms of mean age at first intercourse (17.6 years), median number of life partners (3-4) and median number of sexual partners during the last 12 months (1), but the awareness of sexually transmitted diseases had increased. Their attitudes to using condoms had become more positive and the actual use of a condom had also increased both at the first intercourse and when changing partner, from 40 to 60%. Concerns about safety of oral contraceptives decreased significantly. CONCLUSIONS: This follow-up shows that awareness of sexually transmitted diseases and condom use had increased between 1989 and 1994, possibly as a result of intensified information efforts.

Effects of a single contraceptive Silastic implant containing nomegestrol acetate on ovarian function and cervical mucus production during 2 years.

OBJECTIVE: To study the mechanism of action of Uniplant (South to South Corporation in Reproductive Health, Salvador, Brazil), a single Silastic capsule containing nomegestrol acetate (Lutenyl, Theramex, France) in women during 2 years. DESIGN: Comparison between the hormonal levels, follicular development, cervical mucus (CM) production, and endometrial thickness in the menstrual cycle before implant insertion and at 1, 6, 12, 18, and 24 months after implant insertion. PARTICIPANTS: A total of 15 women of reproductive age were enrolled for the 1st year of use. Twelve of these women continued for a 2nd year of Uniplant use. MAIN OUTCOME MEASURES: Hormonal plasma levels were measured in control cycles and at 1, 6, 12, 18, and 24 months of Uniplant use. Cervical mucus, follicular development, and endometrial thickness also were evaluated. RESULTS: In this study, Uniplant blocks ovulation in 86 percent of cycles studied. Disturbances in follicular growth were observed also. Cervical mucus was scanty and viscous in all women during this study. Endometrial thickness was <8 mm in all cycles studied. CONCLUSION: This study shows that Uniplant is a long-acting contraceptive that probably acts at the hypothalamic-pituitary levels, on the ovary, on CM production, and on the endometrium. These properties suggest the use of Uniplant as a contraceptive agent, especially if one considers the lack of androgenic and metabolic effects and the maintenance of periodic bleeding similar to menstruation.

PIP: A total of 15 healthy women volunteers were enrolled in this study. Their mean age was 23 +or- 1.2 years (range, 18-33 years), mean weight was 55.7 +or- 2.6 kg (range, 40-72 kg), and mean parity was 1.1 (range, 0-4). Venous blood samples were drawn every other day from day eight of the cycle until sonographic evidence of a 12-mm follicle, and then every day until sonographic evidence of follicular rupture and thereafter every other day until the next menstrual bleeding. The capsules were removed at the end of one year of Uniplant use, and a new capsule was inserted in 12 subjects. The blood samples for hormonal analyses were taken after 18 and 24 months of Uniplant use in the 12 women who continued in the study. Levels of luteinizing hormone (LH) were significantly lower than in the control cycles during the observation period (p .01, p .05). According to transvaginal sonography, four different patterns of follicular development were found: normal follicular growth and rupture, persistent follicle, follicular cysts, and no follicular growth. Follicular growth and rupture were observed in 20% of the treated cycles. Persistent follicles were present in approximately 15% of the treated cycles. Follicular cysts were observed in 29% of the cycles studied during 24 months of Uniplant use. All subjects had normal cervical cytology before starting treatment, after 12 months, and after 24 months of Uniplant use. The maximum cervical mucus score for pretreatment cycles was 12.8 +or- 0.4. Endometrial thickness was 8 mm in all cycles studied. 58% (7 of 12) of the women showed a normal menstrual cycle (26 to 32 days). 33% (4 of 12) of the women experienced one or two episodes of amenorrhea (90-134 days), whereas 8.3% of women (1 of 12) experienced episodes of spotting, six times in a period of 24 months of Uniplant use (10-30 days). Before Uniplant insertion, plasma concentration of sex hormone binding globulin was 72.3 nmol/L. After 24 months of Uniplant use, the concentration was 78.0 nmol/L.

Androgen levels in women using a single implant of nomegestrol acetate.

This study was undertaken to evaluate the effects of a single implant containing nomegestrol acetate (Uniplant) on plasma levels of sex hormone-binding globulin (SHBG), testosterone, free testosterone, androstenedione and on blood pressure, body weight, and the development of acne vulgaris. Plasma levels of sex hormone-binding globulin, testosterone, free testosterone and androstenedione were measured. Blood pressure and body weight were determined. The development of acne vulgaris was evaluated. Total testosterone and androstenedione decreased significantly during two years of Uniplant use but all levels were within the normal range. There were no significant differences in sex hormone-binding globulin and free testosterone during 24 months of Uniplant use. All changes observed in this study were within normal range. SHBG was not affected by Uniplant use. No significant increase in androgen levels and in the development of acne vulgaris was observed in these women using nomegestrol acetate implant during two years. Based on these results, it is possible to conclude that Uniplant had no androgenic effect in women during this study.

PIP: In Bahia, Brazil, clinical researchers enrolled 18 women of reproductive age into a clinical study examining the effects of a single contraceptive implant (Uniplant) on plasma levels of sex hormone-binding globulin (SHBG), testosterone, free testosterone, androstenedione, and on blood pressure, body weight, and the development of common acne. They followed the women for 24 months. The implant consisted of silastic tubing filled with 55 mg crystalline, finely ground nomegestrol acetate. The implant did not significantly change the plasma level of SHBG (69.2 nmol/l at baseline and 59.8 nmol/l at 24 months). The plasma level of total testosterone fell from 1.9 to 1.2 nmol/l at 12 months (p 0.01) and to 0.8 nmol/l at 24 months (p 0.01) (p = 0.019 for entire study period). Yet all these levels fell within the normal range. The free testosterone plasma level did not change significantly (2.6 pmol/l at baseline and at 24 months). The plasma level of androstenedione fell steadily throughout the study period (8.7 nmol/l at baseline, 6.2 at 6 months, 4.8 at 12 months, 3.3 at 18 months, and 3.2 at 24 months; p = 0.029), probably a result of ovulation inhibition. Body weight increased from 54.7 kg at baseline to 55.3 kg at 12 months (p 0.01) and to 56 kg at 24 months. Between baseline and 12 months of Uniplant use, both systolic and diastolic blood pressure increased (p 0.01) but did not change significantly thereafter. No woman developed acne. These findings indicate that Uniplant does not induce an androgenic effect in women during two years of use.

Effects of an implant of nomegestrol acetate, a 19-nor-progesterone derivative, on thyroid function.

This study was undertaken to assess tri-iodothyronine (T3), thyroxine (T4), thyroid stimulating hormone (TSH), T3 uptake, free T3 and free T4 in nomegestrol acetate implant (Uniplant) users. A total of eighteen volunteers of reproductive age who wanted to avoid conception were enrolled in the study. All subjects were investigated before starting treatment. Blood samples for hormonal analysis were taken prior to insertion of the implant. Thereafter, blood samples were drawn at 3, 6, 12, 18 and 24 months of Uniplant use. All subjects had used non-hormonal contraceptives for at least 6 months prior to insertion of the implant. The results observed in this study showed that there was no significant difference in tri-iodothyronine (T3), thyroxine (T4) and thyroid stimulating hormone (TSH) during two years of Uniplant use. No significant difference was found in free T3 levels during two years of Uniplant use. A significant decrease was observed in T3 uptake (p < 0.05) in month 24 and in free T4 (p < 0.05) in month 3 of Uniplant use. All changes observed in this study were inconsistent and all levels were within the normal range.

The effects of nomegestrol acetate subdermal implant (Uniplant) on carbohydrate metabolism, serum lipoproteins and on hepatic function in women.

This study was undertaken to assess possible variations in body weight, blood pressure, fasting glucose, HbA1C, insulin, total cholesterol, HDL-C, LDL-C, triglycerides, SGPT, SGOT, GGT and bilirubin in women bearing a single subdermal Silastic implant containing 55 mg (10%) of nomegestrol acetate during two years. A total of eighteen volunteers of reproductive age who desired to avoid conception were enrolled in this study. Subjects were healthy women with no contraindications to hormonal contraception. All women were investigated before starting treatment and were followed up for one year. At the end of one year the capsules were removed and a new capsule was inserted. Fasting blood samples were drawn at 8:00 to 8:30 am twice prior to implant insertion and then at the first, third, sixth and twelfth months and every six months thereafter. Body weight increased from 54.9 +/- 1.5 kg at admission to 55.3 +/- 2.0 kg at 12 months of use (p < 0.05) and to 56.0 +/- 2.7 kg at 24 months of use. A slight increase in both systolic and diastolic blood pressure was recorded at month 12 (p < 0.01). At month 24, blood pressure was not significantly different from admission values. All levels were within the normal range. Insulin, HbA1C, LDL-C and GGT remained unchanged during twenty-four months of Uniplant use. A significant decrease in total cholesterol (p < 0.05) was observed in the third month while a significant decrease in HDL-C (p < 0.01) was observed only in the sixth month of Uniplant use.(ABSTRACT TRUNCATED AT 250 WORDS)

PIP: Possible variations in body weight, blood pressure, fasting glucose, HbA1C (glycosylated hemoglobin), insulin, total cholesterol, high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), triglycerides, serum glutamic pyruvic transaminase (SGPT), serum glutamic oxaloacetic transaminase (SGOT), GGT, and bilirubin were assessed for 2 years. 18 healthy female volunteers with a mean age of 23.0 years and mean parity of 0.9 used a single subdermal Silastic implant (Uniplant) containing 55 mg (10%) of nomegestrol acetate. Fasting blood samples were drawn twice prior to implant insertion and then at the 1st, 3rd, 6th, and 12th months and every 6 months thereafter. Body weight increased from 54.9 kg at admission to 55.3 kg at 12 months of use (p 0.05) and to 56.0 kg at 24 months of use. Both systolic and diastolic blood pressure increased slightly at month 12 (p 0.01). Insulin, HbA1C, LDL-C, and GGT remained unchanged during 24 months of Uniplant use. A significant decrease in total cholesterol (p 0.05) was observed in the 3rd month, while a significant decrease in HDL-C (p 0.01) was observed only in the 6th month of Uniplant use. A significant increase in triglycerides (p 0.05) was observed only in the 12th month. Significant increases in fasting blood glucose levels (p 0.05 and p 0.01) were observed in the 3rd and 6th month, respectively, for 24 months of Uniplant use. Significant decreases in SGOT (p 0.05, p 0.01 and p 0.05) were observed in the 6th, 18th, and 24th months, respectively. A significant decrease in SGPT (p 0.05) was observed in the 18th month of Uniplant use. A significant increase in bilirubin (p 0.05) was observed only in the 3rd month of Uniplant use. Within the normal range, variation of fasting glucose was not correlated with changes in insulin levels and no clinical effects on lipoproteins, carbohydrate metabolism, insulin levels, and on hepatic function were observed in these women.

Differential effects on bone density of progestogen-only methods for contraception in premenopausal women.

The question of differential effects on bone density by two different types of progestogen-only methods for contraception in premenopausal women was addressed. Data from a prospective randomized clinical trial among 22 premenopausal women, age 32.6 (range 20-45 years), who were randomly assigned to either of two treatments with continuous progestogens for contraception were analyzed; depot-medroxyprogesterone acetate (DMPA) or continuous levonorgestrel treatment with subdermal implants (Norplant), respectively. Forearm bone density (BMDprox) increased with 2.94% (p = 0.006) in women who were prescribed levonorgestrel, which was in contrast to stable values in those prescribed depot-medroxy-progesterone acetate; group difference at 6 months for BMDprox 3.4% (95% CI 1.3, 5.5; p = 0.025) and BMDdist 4.1% (95% CI - 1.3, 9.6; p = 0.077). The changes in bone density were consistent with the changes in biochemical indices for bone metabolism; DMPA users showed signs of increased bone turnover and users of levonorgestrel showed increased bone formation with increased levels of both alkaline phosphatase (p = 0.004) and osteocalcin (p = 0.007). The findings suggest an increase in bone density during treatment with levonorgestrel and stable values during short-term administration of DMPA, in standard clinical doses for contraception.

PIP: Researchers randomly allocated 22 premenopausal women aged 20-45 to treatment with either Depo-Provera (150 mg depot-medroxyprogesterone acetate [DMPA] injected intramuscularly every 3 months) or Norplant (30-60 g levonorgestrel/day during 1st year of use) to determine the differences in the short-term effects (at 6 months) on bone mass and bone metabolism. The women, clients of the Family Planning Unit of the University Hospital in Uppsala, Sweden, gave their informed consent to try either of the types of continuous progestogen contraception. The researchers examined biochemical indices for bone metabolism. Alkaline phosphatase and osteocalcin increased significantly in the levonorgestrel group (1.88-2.26 mckat/l [p = 0.004] and 1.22-3.05 mcg/l [p = 0.007], respectively). DMPA increased bone turnover (serum calcium: 2.33-2.38 [p = 0.038]; urine hydroxyproline/creatinine ratio: 12.1-24) and bone formation (serum osteocalcin: 1.2-1.61). Women treated with levonorgestrel experienced a 2.94% increase in forearm bone mineral density (BMDprox) (p = 0.006), while women treated with DMPA experienced an insignificant 0.41% decrease in BMDprox. These changes in BMDprox corresponded with the changes in the biochemical indices for bone metabolism. These findings reveal that treatment with levonorgestrel at standard clinical doses for contraception increases bone density, while treatment with DMPA at standard clinical doses for contraception does not affect bone density.

Ovarian function after seven years' use of a levonorgestrel IUD.

Fifteen women with regular menstrual periods and seven amenorrheic women who had been using a levonorgestrel-releasing (LNg) IUD for more than seven years were studied. For controls, eight women using TCu380Ag IUDs for more than seven years were studied during two complete menstrual cycles. Ovarian function was assessed with hormonal determination and ultrasound examinations. The regularly menstruating women were studied for two complete menstrual cycles and the amenorrheic women for eight weeks. In the regularly menstruating LNg-IUD users, according to progesterone levels, 93% of the cycles were ovulatory but just 58% of these 'ovulatory' cycles showed normal follicular growth and rupture. Follicular cysts and luteinization of regressing follicles were observed in 42% of the 26 'ovulatory' cycles studied. SHBG capacity was decreased in the LNg-IUD users compared with the TCu380Ag users. Progesterone levels were lower in the LNg-IUD users compared with the TCu380Ag users but this difference was not statistically significant. Preovulatory estradiol and LH levels were lower in the LNg-IUD users than in the TCu380Ag users. These differences were not statistically significant. For the amenorrheic women, five had follicular cysts that disappeared spontaneously within 45 days. Two women showed follicular development and rupture. The presence of good cervical mucus was observed in 69% of the ovulatory cycles studied in the LNg-IUD users. This indicates that effects on cervical mucus cannot be the main mechanism of action of the LNg-IUDs. It is concluded that LNg-IUDs may exert a contraceptive effect in many different ways, such as inhibition of ovulation, endometrial changes preventing implantation, alteration of physical and chemical properties of cervical mucus affecting sperm transport and subtle disturbances in hypothalamic pituitary ovarian function, resulting in alterations of follicular development and rupture.

Antichlamydial activity of vaginal secretion.

OBJECTIVE: The purpose of this study was to investigate the possible antichlamydial activity of vaginal secretion and to partially characterize the inhibitory principle. STUDY DESIGN: Vaginal secretions obtained from 156 women attending a family planning or gynecologic outpatient clinic for contraceptive advice were studied for the influence on the inclusion formation of Chlamydia trachomatis in cycloheximide-treated McCoy cell cultures. RESULTS: Vaginal secretions from 156 women inhibited the inclusion formation of Chlamydia trachomatis. The inhibition was concentration dependent and the inhibitory principle had a molecular weight of < 10,000 d. It was heat labile. It was not related to antichlamydial antibodies in vaginal secretions. Only three (2%) of the women had a positive culture for Chlamydia trachomatis. Three had immunoglobulin A and three had immunoglobulin G antichlamydial antibodies in vaginal secretions. Secretions of those with a vaginal pH of 3.5 to 4.5 decreased the chlamydial inclusion count by 75% compared with controls. The corresponding percentage for those with a pH of 5.0 to 6.0 was 48% and for those with pH > 6 was 33%. Vaginal secretions of oral contraceptive users and nonusers did not differ in the capacity to decrease the chlamydial inclusion count, p > 0.01. CONCLUSIONS: When vaginal secretions were added to McCoy cell cultures infected by Chlamydia trachomatis, the chlamydia inclusion number decreased. There was a correlation between pH of the vaginal secretion and the inhibitory principle. Oral contraceptive use had no influence on the inhibition.

Effects of specially tailored information on Swedish university students' sexual behavior.

In independent surveys concerning sexual behavior among university students in Uppsala, Sweden, in 1989 and 1990, we found that condoms were infrequently used and that up to 25% of the sexually experienced students had a history of having had at least one sexually transmitted disease (STD). We targeted an information campaign toward the same students (approximately 20,000) in 1990. Our aims were (1) to increase the knowledge of STDs and alert the students to the high frequency of STDs in the student population, (2) to encourage students to have an STD checkup at the local STD clinic, and (3) to induce a positive attitude toward condoms. We evaluated the effects of the campaign, using before and after classroom surveys, a separate survey of students who attended the STD clinic, and a focus group analysis. Although the information campaign was successful, in that students became more aware of STDs and showed increased knowledge about the high frequency of STDs in their own population, fewer than 1% of the target population went for an STD checkup at the local STD clinic. Overall, the campaign was well received by the students but failed to induce any measurable changes in attitudes during the short observation period.

Plasma concentrations of medroxyprogesterone acetate, estradiol and estrone following oral administration of Klimaxil, Trisequence/Provera and Divina. A randomized, single-blind, triple cross-over bioavailability study in menopausal women.

The absorption of estradiol and medroxyprogesterone acetate was investigated in a randomized single-blind, triple cross-over study, in 12 menopausal women, for four different HRT drugs (Klimaxil, a combination tablet containing 17 beta-estradiol 2 mg and medroxy-progesterone acetate 5 mg; Divina, a combination tablet containing 17 beta-estradiol valerate 2 mg and medroxyprogesterone acetate 10 mg; Trisequence, a triphasic preparation containing 17 beta-estradiol 2 mg in the first phase; Provera, a tablet containing medroxyprogesterone acetate 5 mg). Trisequence and Provera were ingested simultaneously. In conclusion, there was no statistically significant difference between the drugs with respect to the estradiol levels. The estrone concentration, however, differed between the different drugs. The serum concentration was higher after intake of tablets containing estradiol than after intake of tablets containing the valerate ester. There was a significant increase in the MPA levels between periods 1 and 3. Finally, Divina produced higher MPA concentrations than Klimaxil and the combination of Trisequence and Provera, although the mean AUC was not twice as high, as might have been expected.

Antichlamydial activity of cervical secretion in different phases of the menstrual cycle and influence of hormonal contraceptives.

Cervical secretion from three groups of asymptomatic women, either being oral contraceptive (OC) non-users or users (ethinylestradiol plus desogestrel or levonorgestrel), was tested for its capacity to prevent Chlamydia trachomatis, serotype I, from forming inclusions in cycloheximide-treated McCoy cells. The non-user groups were comprised of 12 women from whom cervical secretion was collected twice weekly during the menstrual cycle and 15 women from whom cervical secretion was collected once or twice weekly. The OC users included 66 women from whom cervical secretion was collected once or twice during their menstrual cycle. Cervical secretion from the non-users produced a decrease in the chlamydial inclusion count by 70%-90% during the first 3 weeks of the menstrual cycle, as compared with the fourth and fifth week when the reduction was 56%-68% (p < 0.001). Secretion from the OC users showed a more effective decrease in the inclusion count during the first 3 weeks of the menstrual cycle, as compared with samples obtained at the fourth and fifth weeks, i.e. 15%-35% vs. 20%-25% (p < 0.001). Cervical secretion of the non-users as compared to the users produced a significant decrease in the inclusion count, viz. 70%-90% vs. 15%-35% (p < 0.001) during the first 3 weeks as compared with 56%-68% vs. 20%-25% (p < 0.001) in the fourth or fifth week. The study suggests that natural resistance to genital chlamydial infection can differ during the menstrual cycle and it may be influenced by oral contraceptive use.