Modeling the photocatalytic mineralization in water of commercial formulation of estrogens 17-ß estradiol (E2) and nomegestrol acetate in contraceptive pills in a solar powered compound parabolic collector.

Endocrine disruptors in water are contaminants of emerging concern due to the potential risks they pose to the environment and to the aquatic ecosystems. In this study, a solar photocatalytic treatment process in a pilot-scale compound parabolic collector (CPC) was used to remove commercial estradiol formulations (17-ß estradiol and nomegestrol acetate) from water. Photolysis alone degraded up to 50% of estradiol and removed 11% of the total organic carbon (TOC). In contrast, solar photocatalysis degraded up to 57% of estrogens and the TOC removal was 31%, with 0.6 g/L of catalyst load (TiO2 Aeroxide P-25) and 213.6 ppm of TOC as initial concentration of the commercial estradiols formulation. The adsorption of estrogens over the catalyst was insignificant and was modeled by the Langmuir isotherm. The TOC removal via photocatalysis in the photoreactor was modeled considering the reactor fluid-dynamics, the radiation field, the estrogens mass balance, and a modified Langmuir-Hinshelwood rate law, that was expressed in terms of the rate of photon adsorption. The optimum removal of the estrogens and TOC was achieved at a catalyst concentration of 0.4 g/L in 29 mm diameter tubular CPC reactors which approached the optimum catalyst concentration and optical thickness determined from the modeling of the absorption of solar radiation in the CPC, by the six-flux absorption-scattering model (SFM).

An open-label study of subdermal implants of estradiol-only versus subdermal implants of estradiol plus nomegestrol acetate: effects on symptom control, lipid profile and tolerability.

OBJECTIVE: To compare the effects of continuous 17-beta estradiol-only silastic implants with those of continuous 17-beta estradiol plus continuous nomegestrol acetate silastic implants on symptom control, lipid profile and tolerability in postmenopausal women. METHODS: This was an open-label, parallel-group study. Women with and without uterus and no contraindications to hormone therapy (HT) in this study, we consider as HT the replacement of Estrogens-only and Estrogens + Progestogens Therapy, were enrolled. Each subject was assigned to receive four 17-beta estradiol-only silastic implants (women without uterus), or four 17-beta estradiol plus one nomegestrol acetate silastic implant (women with intact uterus), for 1 year. RESULTS: A total of 40 subjects were enrolled and received, the silastic implants of which 40 (100.0%) subjects completed the study (n = 20, estradiol only; n = 20, estradiol plus nomegestrol acetate). The incidence of postmenopausal symptoms decreased significantly. No significant decreases in total cholesterol (1.3%), low-density lipoprotein cholesterol (1.1%), triglycerides (1.2%) and fasting glucose ((1.3%) serum levels were observed in both groups, whereas high-density lipoprotein (HDL) cholesterol increased significantly (2.8%), during the study in both groups. The incidences of adverse events were similar in both treatment groups. CONCLUSIONS: Women treated with 17-beta estradiol-only silastic implants or 17-beta estradiol plus nomegestrol acetate silastic implants showed significant improvement of postmenopausal symptoms, including urogenital and sexual health symptoms and a significant increase in HDL cholesterol and no significant differences in other lipid profiles and tolerability.

Effects of a single Silastic contraceptive implant containing nomegestrol acetate (Uniplant) on endometrial morphology and ovarian function for 1 year.

PURPOSE: This study was undertaken to evaluate the effects of a subdermal implant containing nomegestrol acetate (Uniplant) on endometrial histology and ovarian function. METHODS: Twenty healthy female volunteers of reproductive age were included and completed a menstrual diary throughout the study. Hysteroscopy, transvaginal sonography and blood sampling were performed prior to implant insertion (control cycle) and following 6 and 12 months of Uniplant use. Transvaginal sonography was performed every other day from Day 8 of the cycle up to the obtainment of sonographic evidence of a 12-mm follicle, then every day until the obtainment of sonographic evidence of follicular rupture and thereafter every other day until the next menstrual bleeding. Blood samples were taken for the measurement of estradiol, follicle-stimulating hormone, luteinizing hormone and progesterone on the same days on which transvaginal sonography was performed. The implants were removed after 1 year. RESULTS: Twenty percent of cycles were ovulatory, and 80% were anovulatory. The development of persistent nonluteinized follicle occurred in 40% of all cycles studied, inadequate luteal phase occurred in 20% of cycles and no follicular development occurred in 40%. Endometrial thickness remained below 8 mm in all cycles studied. Alterations in endometrial vascularization were observed in all treated cycles. CONCLUSION: Our results suggest that this long-acting contraceptive method affects follicular growth and endometrial vascularization, disrupts endometrial architecture and leads to inadequate luteal phase.

Inibidores da aromatase no câncer de mama: da doença metastática ao tratamento adjuvante / Aromatase inhibitors in breast cancer: from metastatic disease to adjuvant treatment

Os tratamentos hormonais continuam a ter papel importante no manejo clínico das pacientes com câncer de mama. Entre os avanços mais recentes, os inibidores da aromatase de terceira geração vêm ocupando lugar de destaque no contexto da doença metastática. A aromatase, presente em diversos tecidos, é responsável pela conversão de andrógenos em estradiol e estrona. Antes da menopausa, a maior parte dos estrógenos femininos se origina nos ovários. Com a insuficiência ovariana, as glândulas supra-renais passam a ser a principal fonte de andrógenos, que são convertidos pela aromatase em estrógenos; esta conversão ocorre em tecidos periféricos como gordura, músculos, fígado e o próprio tumor de mama. A inibição da aromatase é uma estratégia com base racional sólida, e comprovadamente eficaz no sentido de reduzir os níveis séricos de estrógenos em mulheres pós-menopausa. Os inibidores de aromatase de primeira e segunda geração caracterizaram-se por alta toxicidade ou baixa eficácia, quando comparados ao tamoxifeno. No entanto, o tamoxifeno apresenta, além de sua ação antiestrogênica, um efeito pró-estrogênico, responsável por efeitos colaterais, tais quais proliferação do endométrio e fenômenos tromboembólicos. Estudos recentes, discutidos neste artigo, demonstraram a superioridade dos inbidores da aromatase de terceira geração, com relação ao megestrol, no tratamento hormonal de segunda linha do câncer de mama metastático em mulheres pós-menopausa. Além disto, estas drogas têm conquistado papel de destaque no tratamento de primeira linha da doença metastática, no tratamento neo-adjuvante, e no tratamento adjuvante de pacientes com câncer de mama.

Carbohydrate metabolism in sickle cell patients using a subdermal implant containing nomegestrol acetate (Uniplant).

Uniplant, a second-generation contraceptive implant, has been demonstrated to promote a significant improvement in the overall well-being of women with sickle cell anemia. It has been suggested that the discrete increase in blood glucose levels observed in Uniplant users could be a contributory factor for clinical improvement. Ten healthy sickle cell patients were enrolled in the study. An oral glucose tolerance test was performed prior to implant insertion and at 1, 6, and 12 months of therapy. Blood glucose and insulin were measured before and at 30, 60, 120, and 180 min after a 75-g glucose load. The glucose and insulin areas under the curves were calculated. Fasting glycosylated hemoglobin was also measured. No significant changes were observed in glycosylated hemoglobin, glucose or insulin. We conclude that Uniplant is a safe contraceptive for sickle cell patients.

Nomegestrol acetate contraceptive implant use by women with sickle cell disease.

OBJECTIVE: To assess the contraceptive effectiveness, safety, and potential health benefits of nomegestrol acetate contraceptive implant use by women with homozygous sickle cell disease (hemoglobin SS). METHODS: This was a prospective observation before and after insertion of nomegestrol acetate of 20 women with sickle cell disease (test group) compared with 10 women with similar sociodemographic backgrounds. Changes in hematologic and biochemical parameters and symptoms of sickle cell crisis were measured during 12 months of observation. RESULTS: After use of nomegestrol acetate for 1 to 9 months, the women in the test group had symptomatic improvement, with no crisis that required hospitalization and no deaths. Sickle cell symptoms persisted in the women in the control group, with 1 recorded death. Increases in F-cell and fetal hemoglobin parallel the observed clinical improvement in the treated women. There were no adverse hematologic or biochemical changes associated with the use of nomegestrol acetate implants. CONCLUSION: Nomegestrol acetate appears to be a safe and appropriate contraceptive for women with sickle cell disease, showing evidence of being a "stimulant" for F-cell reactivation, independent of F hemoglobin total production increase.

Contraceptive potential of a mifepristone-nomegestrol acetate sequential regimen in women.

The effectiveness of a sequential regimen consisting of mifepristone, 10 mg/day for 15 days, followed by nomegestrol acetate (NOMA), 5 mg/day for the next 13 days, for inhibiting ovulation and maintaining regular bleeding cycles was assessed in 10 surgically sterilized volunteers who were followed for one pretreatment and three treated cycles. Hormonal determinations in blood and urine, ovarian ultrasonography, bleeding records in all cycles and an endometrial biopsy taken on day 22-25 of the third treatment cycle were used to monitor the effects of treatment. During treatment, 24 monophasic (no sustained progesterone rise above 12 nmol/l) and six biphasic cycles were recorded. Nine follicular ruptures were detected echographically in these 30 treated cycles, five of which occurred in monophasic cycles. All follicular ruptures occurred on days 1-7 of NOMA treatment. Echographic and endocrine features of ovulatory cycles were both present in only four treated cycles (13.3%). Development of a secretory endometrium was achieved in all cases, but it was always irregular. Regular withdrawal bleeding occurred in all subjects and no adverse reactions were recorded. The ovarian and endometrial effects of this regimen justify testing its contraceptive effectiveness in phase 2 clinical trials.

PIP: This study investigated the efficacy of mifepristone, 10 mg/day for 15 days, followed by nomegestrol acetate (NOMA), 5 mg/day for the next 13 days, for inhibiting ovulation and maintaining regular bleeding cycles in 10 surgically sterilized volunteers. To monitor the effects of treatment, hormonal determinations in blood and urine, ovarian ultrasonography, bleeding records in all cycles and endometrial biopsy were taken on day 22-25 of the third treatment cycle. About 24 monophasic and 6 biphasic cycles were recorded during treatment. About 9 follicular ruptures were echographically detected in these 30 cycles, 5 of which occurred in monophasic cycle. All follicular ruptures occurred in days 1-7 of NOMA treatment. Echographic and endocrine features of ovulatory cycles were both present in only four treated cycles (13.3%). Development of a secretory endometrium was achieved in all cases, but it was always irregular. Regular withdrawal bleeding occurred in all subjects and no adverse reactions were observed. The ovarian and endometrial effects of this regimen justify testing its contraceptive effectiveness in phase 2 clinical trials.

Neuroendocrine mechanism of anovulation in users of contraceptive subdermal implant of nomegestrol acetate (Uniplant).

OBJECTIVE: To evaluate a nomegestrol acetate subdermal contraceptive implant's (Uniplant; Thermex, Monaco) effect on the hypothalamus-pituitary-ovarian axis. DESIGN: A prospective clinical trial. SETTING: San Borja-Arriarán Clinical Hospital, University of Chile, School of Medicine. PATIENT(S): Normally cycling healthy women. INTERVENTION(S): Insertion of Uniplant. MAIN OUTCOME MEASURE(S): Luteinizing hormone pulse and endocrine profiles were assessed before, 48 hours after insertion, and after prolonged use of the implant. RESULT(S): Anovulation was noted in 100% of users in the first month. Seventy percent of subjects demonstrated follicular development with the absence of ovulation and an endocrine profile similar to the follicular phase: (LH pulse/8 hours 6.85 +/- 0.67, LH amplitude 3.54 +/- 0.65 mIU/mL (conversion factor to SI unit, 1.00), and E2 193 +/- 29.4 pg/mL (conversion factor to SI unit, 3.67), whereas 30% demonstrated no follicular activity with an endocrine profile similar to the luteal phase: (LH pulse/8 hours; 3.66 +/- 0.66, LH amplitude 5.76 +/- 1.73 mIU/mL, and E2 67.5 +/- 4 pg/mL. Clinical characteristics, serum gonadotropin concentration, and LH pulse characteristics failed to predict which subjects would initiate or remain devoid of follicular activity. CONCLUSION(S): Uniplant results in anovulation via two mechanisms: hypothalamic suppression in subjects who lack follicular development, and likely suppression of the pituitary LH surge in subjects who initiate follicular activity.

PIP: Findings are reported from a study of a nomegestrol acetate subdermal contraceptive implant's (Uniplant) effect upon the hypothalamus-pituitary-ovarian axis. 10 normally cycling healthy women aged 22-36 years requesting a contraceptive method at San Borja-Arriaran Hospital's family planning clinic participated in the prospective clinical trial. Luteinizing hormone pulse and endocrine profiles were assessed before insertion, 48 hours after insertion, and after prolonged use of the implant. Anovulation was noted in 100% of users in the first month. 70% of subjects demonstrated follicular development with the absence of ovulation and an endocrine profile similar to the follicular phase, while the remaining 30% demonstrated no follicular activity with endocrine profile similar to the luteal phase. Clinical characteristics, serum gonadotropin concentration, and LH pulse characteristics failed to predict which subjects would initiate or remain devoid of follicular activity. Uniplant therefore results in anovulation through hypothalamic suppression in subjects who lack follicular development and the likely suppression of the pituitary LH surge in subjects who initiate follicular activity.

Changes in the menstrual bleeding of users of a subdermal contraceptive implant of nomegestrol acetate (Uniplant) do not influence sexual frequency, sexual desire, or sexual enjoyment.

OBJECTIVE: To evaluate the effect of menstrual changes induced by a nomegestrol acetate subdermal contraceptive implant (Uniplant; Thermex, Bahia, Brazil) on users' sexuality. DESIGN: Prospective observational survey. SETTING: San Borja-Arriarán Hospital, University of Chile, School of Medicine. PATIENT(S): Normally cycling healthy women and their partners. INTERVENTION(S): Structured interview before and during use of the contraceptive. MAIN OUTCOMES MEASURE(S): Sexual frequency, desire, and enjoyment; perception of health; and contraceptive satisfaction. RESULT(S): During the use of the implant more women reported irregular cycles (32% versus 11%) and vaginal spotting (38% versus 19%). Frequency of sexual relations was unchanged (2.3 versus 2.5/wk) but the percent of couples engaging in sexual relations during vaginal spotting increased (28% versus 11%). There was no significant difference in the percent of men or women who reported an increase, or decrease, in perceived sexual desire, sexual enjoyment, or perception of health during the use of Uniplant. CONCLUSION(S): Despite the alterations in menstrual cyclicity and the occurrence of spotting, the use of a contraceptive subdermal implant of nomegestrol acetate did not effect desire for, enjoyment of, or frequency of sexual relations in users.

PIP: Findings are presented from a study evaluating the effect of menstrual changes induced by a nomegestrol acetate subdermal contraceptive implant (Uniplant) on users' sexuality. The Uniplant implant evaluated is manufactured by Thermex of Bahia, Brazil. New subjects enrolled in a phase III clinical trial of the implant at San Borja-Arriaran Hospital, University of Chile, School of Medicine were observed prospectively. The participants were 118 normally cycling healthy women of median age 28 years and 60 male partners of median age 31 years. A structured interview was held before and during use of the contraceptive. Before insertion of the implant, 11% of the women reported irregular menstrual cycles, 19% reported vaginal spotting, and 11% of the couples reported engaging in sexual relations during vaginal spotting. During use of the implant, 32% of the women reported irregular cycles, 38% reported vaginal spotting, and 28% of the couples reported engaging in sexual relations during vaginal spotting. The frequency of sexual relations remained unchanged at 2.3-2.5 acts of coitus per weeks. There was no significant difference in the percentage of men or women who reported an increase or decrease in perceived sexual desire, sexual enjoyment, or perception of health during the use of Uniplant.

Results of a user satisfaction study carried out in women using Uniplant contraceptive implant.

A study of the acceptability of Uniplant, a 12-month single implant of nomegestrol acetate, included 819 women from Africa, Latin America, and China, participating in a clinical trial of Uniplant. A standard, pre-coded questionnaire was specially designed for this purpose and applied at the moment of removal of implant, either at the end of 12 months of use or at the time of discontinuation for whatever reason. The level of satisfaction proved high when users' comparison with their previous contraceptive method, users' recommendation of Uniplant to others, users' intention to use the method in the future, and service satisfaction were taken into consideration. Uniplant was considered easy to use, safe (low risk of pregnancy), and also to cause fewer side effects than other methods. When asked about the least liked feature of Uniplant, almost half the respondents said that there was nothing that they disliked and about one-third mentioned the changes in their menstrual pattern. However, according to the clinical trial, over half of the Uniplant users have bleeding patterns similar to untreated cycles. The majority of respondents did not feel any discomfort during the procedure of insertion and removal of the implant. About 70% of patients in the study stated that they required contraception for more than one year and most of these women said that they did not mind having to change the implant every year.

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.

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.

Multicenter clinical trial on the efficacy and acceptability of a single contraceptive implant of nomegestrol acetate, Uniplant.

Uniplant, a single Silastic implant containing nomegestrol acetate, provides contraceptive efficacy for one year. Uniplant use for one year was studied in 1,803 healthy women of reproductive age, enrolled from 10 centers in 9 countries, after informed consent. Implants were placed subdermally either in the upper arm or in the gluteal region. Two-hundred-seventy-six subjects discontinued prior to completing one year of study. Cumulative discontinuation rate at 12 months was 15.72%. Medical reasons for discontinuation were principally menstrual-related. Fifteen pregnancies occurred during the one year study period, resulting in a 12-month net cumulative pregnancy rate of 0.94%. Approximately 56% of subjects using Uniplant had bleeding patterns similar to normal menstruation. Results from this study confirm that Uniplant is an efficient, well tolerated, 12-month contraceptive implant, with the advantage of easier insertion and removal of the single implant compared to other multiple implant methods.

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.

Contraceptive implants.

Available contraceptive implants appeal to women of diverse cultural and socioeconomic background because they offer long-term contraception, safety, effectiveness, reversibility and lack of estrogenic side-effects. Experience with Norplant I indicates that despite some side-effects the continuation rate is the highest for any reversible method of contraception. Disruption of the menstrual cycle is the main reason for discontinuation, hence research effort needs to focus on the mechanism of progestogen-induced endometrial bleeding and appropriate therapy. Implant service programs should have trained and skilled personnel who can provide adequate counseling that complements any public education effort and also provides effective services. Because contraceptive implants offer no protection against sexually transmitted infections, those who engage in high-risk sexual behavior should be encouraged to use condoms as well.

PIP: Women of diverse cultural and socioeconomic levels choose available contraceptive implants because of long-term contraception, safety, effectiveness, reversibility, and lack of estrogenic side effects. Norplant is a safe, effective method of reversible fertility regulation, as shown by studies in several countries with diverse sociocultural and demographic profiles. However, the major shortcoming is menstrual disorders, which cause about half of all discontinuations. Since the US Food and Drug Administration approved the use of Norplant in December 1990, acceptability among the diverse general population was largely dependent on the intensity of counseling. Removal rates of Norplant implants in adolescents were similar to those for mature women, and in general implant acceptability, continuation, and tolerance of side effects were high and comparable among adolescent and adult acceptors. Abnormal bleeding patterns still represent the most common complaint and reason for discontinuation among adolescents and adults. The insertion and removal of Norplant requires appropriate training of physicians and nonphysicians who plan to provide Norplant services. Norplant II consists of 2 silastic rods each containing 70 mg levonorgestrel. Phase III clinical trials in 1466 Indian women observed for 52,849 woman-months of use resulted in a method failure rate of 6.8 per 100 users and a continuation rate of 42.1 per 100 users at 5 years of use. Nomegestrol acetate implant is a second-generation single silastic implant containing 55 mg nomegestrol acetate with contraceptive effectiveness of 1-year duration. Implanon implant is a single ethylene vinyl acetate rod containing 60 mg 3-ketodesogestrel with more progestogenic and less androgenic activity than levonorgestrel and 2-year effectiveness. ST-1435 implant contains ST-1435, a synthetic progestin which inhibits ovulation when administered parenterally but not orally. If appropriate counseling is provided implants can be a popular method of contraception in different parts of the world.

One year contraception with a single subdermal implant containing nomegestrol acetate (Uniplant).

One single silastic capsule containing nomegestrol acetate, Uniplant, was inserted subcutaneously in 100 women of reproductive age who desired to avoid conception. Insertions and removals of the capsules were made in the gluteal region following intracutaneous local anesthesia with 2% procaine. Eighty women completed one year of use. Eleven women bore the implant for 6-11 months. A total of 1,085 women-months were recorded. One pregnancy occurred, resulting in a Pearl Index of 1.1. Bleeding episodes similar to menstruation occurred in all women but the degree of regularity varied from subject to subject. Amenorrhea developed in the range of 14-18% during the first six months of use but declined to less than 10% during the last six months. Menorrhagia likewise was higher in the first six months (18% in the first month) but fell to less than 10% during the last six months. Spotting was 5% or less. Of the twenty women who did not complete one year of use, nine discontinued because they found other methods were either more practical or less revealing. Three discontinued because of bleeding irregularities, three desired to become pregnant, one became pregnant. Other complaints included dizziness, headache, increased blood pressure, loss of libido, painful breasts and nausea. Over half of the women indicated their desire to continue using the single implant as a contraceptive.

Avaliaçäo anátomo histopatológica do efeito do acetato de medroxiprogesterona e do acetato de megestrol sobre o útero de cadelas adultas / Anatomo histopathologic evaluation of the effect of medroxiprogesterone acetate and megestrol acetate on the uterus of adult bitches

No presente experimento foram utlizadas 18 fêmeas caninas adultas, clinicamente sadias, sem sintomas clínicos de estro, as quais foram subdivididas aleatoriamente em 6 grupos contendo 3 animais cada. Após biópsia uterina para controle, foi administrado acetato de medroxiprogesterona nas fêmeas dos grupos I, II e III e acetato de megestrol nas fêmeas dos grupos IV, V, VI. Observou-se que ambas as drogas utilizadas induziram a ocorrência de endometrite, porém este foi mais discreto nos animais dos grupos IV, V e VI. Näo foi registrada a ocorrência de poliúra, polidipsia, distençäo abdominal, corrimento vaginal purulento ou sanguinolento, leucocitose e anemia

Ocular toxicity of tamoxifen.

Tamoxifen is a preferred agent for the treatment of breast cancer. While efficacious, it is not without serious side effects. Ocular toxicity to the cornea, retina, and optic nerve have been reported. We present a case of tamoxifen retinopathy and emphasize the need for periodic ophthalmologic examinations to prevent loss of vision.