Vaginal States: Detection of Conversion Processes in Women Using Contraception and Characterization of Vaginal Lactobacillus Species.

BACKGROUND: The vaginal microenvironment, regulated by an immune system, can be protected or altered by many factors, including contraceptive methods. OBJECTIVE: The objective of this study is to evaluate the impact of contraceptive methods on the basic vaginal states (BVSs) and to identify culturable vaginal Lactobacillus species. METHODS: This is a prospective, consecutive, longitudinal, and descriptive study. The vaginal contents of 208 women were sampled prior to initiating contraception and six months later. The BVSs were established using the balance of vaginal content (BAVACO) methodology that evaluates microbiota and vaginal inflammatory reaction (VIR). Lactobacillus species were characterized by biochemical tests and mass spectrometry. The following contraceptive methods were evaluated: combined oral contraceptive pill (COCP), condom (CON) and rhythm method (RHYT). McNemar's test was used. RESULTS: Of the 208 women, 171 attended both examinations. In the COCP group (n=127), 83 vaginal contents maintained a normal microbiota, 1 sample became dysbiotic, and 37/43 dysbiotic microbiota samples reverted to normal (p<0.0001). A conversion to BVS with VIR was detected in the CON group (n=31) (p=0.001). The RHYT group (n=13) maintained its initial BVSs. The predominant Lactobacillus species found were L. crispatus and L. gasseri, with a trend toward a positive association between L. crispatus and COCP (OR=2.82; p=0.058). CONCLUSION: Hormone administration corrected the dysbiosis and preserved a normal BVS. The CON increased the VIR. The protection of the microbiota observed in the rhythm method probably responds to a systemic hormonal influence. The trend toward a positive association between COCP and L. crispatus, with its protective properties, evidenced an effective hormonal relationship.

Use of an estradiol-based combined oral contraceptives has no influence on attentional bias or depressive symptoms in healthy women.

Combined oral contraceptive (COC) use is associated with small, albeit significant, increases in mental symptom scores, predominantly irritability, depressed mood, and anxiety. Yet, randomized prospective trials are needed to better characterize the women at risk for COC-induced negative mood change. Thus, the primary aim of this sub-study to a placebo-controlled randomized trial was to determine whether COC use influences emotional interference by negative and positive stimuli. Secondly, we wanted to evaluate what factors would predict depressive symptoms at the end of the trial, taking personality factors, history of mental disorders and other demographic factors into account. Sixty-nine women were included, randomized to three cycles of treatment with a COC (1.5 mg estradiol and 2.5 mg nomegestrolacetate) or placebo. An emotional verbal Stroop task was used to measure interference of emotional stimuli, in which participants were asked to only name the color of a presented word, while ignoring the meaning of the word. Four different word categories were used; neutral, positive, depression, and anxiety. For the second aim of the study, rating on the Montgomery-Åsberg Depression Rating Scale during the final days of the trial was used as outcome. We found no interaction between emotional verbal Stroop word category and treatment, indicating that COC treatment did not evoke any differences in emotional interference to the three word categories. Significant predictors for depressive symptoms at the end of the trial were trait anxiety at baseline and prior adverse mood effects by hormonal contraceptive use. Treatment (i.e. whether women had been treated with the COC or placebo) did not play a role in predicting depression scores at the end of the trial. In conclusion, we found no evidence that combined oral contraceptive use is associated with impaired cognitive-emotional processing. Instead, the main predictors of self-rated depression at the end of the trial were baseline trait anxiety and previous mental symptoms during hormonal contraceptive use.

Oral contraceptive use and saliva diurnal pattern of metabolic steroid hormones in young healthy women.

BACKGROUND: The impact of oral contraceptives (OCs) on the saliva diurnal pattern of metabolic steroid hormones remained unknown. STUDY DESIGN: Saliva samples were taken from young healthy women (11 OC users, 10 non-OC users) to analyze cortisol, dehydroepiandrosterone (DHEA) and testosterone 4 times (days 1, 8, 15 and 22) over one menstrual cycle. RESULTS: OC use decreased saliva testosterone concentrations (p<.01) under all conditions of day and time, but not saliva cortisol. OC also decreased saliva DHEA concentrations during the first part of the day (p<.05), with a dampened amplitude in its diurnal pattern. CONCLUSION: The clinical relevance requires further study.

New metabolites from fungal biotransformation of an oral contraceptive agent: methyloestrenolone.

Fungal cell cultures were used for the first time for the biotransformation of methyloestrenolone (1), an oral contraceptive. Fermentation of 1 with Macrophomina phaseolina, Aspergillus niger, Gibberella fujikuroi, and Cunninghamella echinulata produced eleven metabolites 2-12, six of which 2-5, 11 and 12 were found to be new. These metabolites were resulted from the hydroxylation at C-1, C-2, C-6, C-10, C-11, and C-17α-CH3, as well as aromatization of ring A of the steroidal skeleton of substrate 1. The transformed products were identified as 17α-methyl-6ß,17ß-dihydroxyestr-4-en-3-one (2), 17α-(hydroxymethyl)-11ß,17ß-dihydroxyestr-4-en-3-one (3), 17α-methyl-2α,11ß,17ß-trihydroxyestr-4-en-3-one (4), 17α-methyl-1ß,17ß-dihydroxyestr-4-en-3-one (5), 17α-methyl-11α,17ß-dihydroxyestr-4-en-3-one (6), 17α-methyl-11ß,17ß-dihydroxyestr-4-en-3-one (7), 17α-methyl-10ß,17ß-dihydroxyestr-4-en-3-one (8), 17α-(hydroxymethyl)-17ß-hydroxyestr-4-en-3-one (9), 17α-methylestr-1,3,5(10)-trien-3,17ß-diol (10), 17α-methyl-3,17ß-dihydroxyestr-1,3,5(10)-trien-6-one (11), and 17α-methyl-6ß,10ß,17ß-trihydroxyestr-4-en-3-one (12).

Comparison of serum and cervical mucus hormone levels during hormone-free interval of 24/4 vs. 21/7 combined oral contraceptives.

BACKGROUND: This study analyzes levels of progesterone, estradiol, norethindrone (NET) and ethinyl estradiol (EE) in serum and levels of NET in cervical mucus on the last day of the hormone-free interval (HFI) in users of 24/4 [norethindrone acetate (NETA)/EE-24] vs. 21/7 (NETA/EE-21) regimens. STUDY DESIGN: This was a randomized controlled, crossover, equivalency trial. Subjects were randomized to receive NETA/EE-24 or NETA/EE-21 for 2 months and then switched between study drugs. Blood and cervical mucus samples were obtained on Days 12-16 and on the last day of the HFI. RESULTS: From April 2010 to November 2011, 32 subjects were enrolled with 18 subjects completing all study visits. There were no statistically significant differences in either day 12-16 (p=.54) or last hormone-free day (p=.33) cervical mucus NET concentrations between the regimens. On the last day of the HFI, median serum progesterone levels did not differ significantly; however, users of NETA/EE-24 had higher levels of serum NET (p<.001) and users of NETA/EE-21 had higher levels of serum estradiol (p=.01). CONCLUSION: This data supports the fact that inhibition of the pituitary-ovarian axis occurs during oral contraceptive use and during the HFI. We demonstrated that a reduced HFI of 4 days resulted in better suppression of the ovarian hormone production, thereby reducing the risk of ovulation and potential contraceptive failure.

Antibiotics and oral contraceptives: new considerations for dental practice.

The aim of this paper is to highlight a change in guidance relating to possible interactions between antibiotics and oral contraceptives. Until recently, dentists have been advised to warn women taking the combined oral contraceptive pill of the routine need to use additional contraceptive measures while taking courses of broad spectrum antibiotics. Recent guidance relating to this issue has changed and dentists may not be aware of this. This paper reminds dentists of the previous guidelines and related evidence, reviews the pharmacokinetics of hormonal contraception and presents them with the latest evidence-based guidance. This should change their clinical practice.

Assessment of the activity of an oral contraceptive on the levels of oxidative stress and changes in oxidative stress after co-treatment with two different types of physiological modulators with antioxidant action.

BACKGROUND: The aims of this research were to document the nature of oxidative stress (OS) while taking an estrogen/progestagen-combined oral contraceptive (OC) and to evaluate the action of two different products composed of a combination of antioxidant, vitamins and natural products in physiological quantity and classified as antioxidant/food supplement. For this reason, the two products are classified as physiological modulators (PM), able to restore the balance between antioxidants and reactive oxygen species in the organism. STUDY DESIGN: The Reactive Oxygen Metabolites-derived compound test, a photometric assay that measures the hydroperoxides levels in biological fluids, was used to determine the OS. OS was analyzed every 3 days (from t(1) to t(27)) for 28 days on 10 healthy volunteers during three successive OC treatment cycles with a contraceptive (Microgynon®: ethinylestradiol 50 mcg plus levonorgestrel 125 mcg). In the first cycle, the OC was administered by itself; in the successive two cycles, the OC was administered in association in an open crossover study with two different types of PMs with antioxidant action. The main difference in the composition of the two products is the presence/absence of catechins from green tea. RESULTS: With just OC treatment, all the volunteers showed an increase in the OS values from 240±22.3 (mean±SD) Carratelli Units. (normal value) up to values >400 Carratelli Units (severe OS), then returned to normal when the OC therapy was suspended. The concomitant use of the two PMs showed that only the product containing green tea catechins was able to reduce the OS values, on average, by approximately 50% (t test p<.05). CONCLUSION: We conclude that to control the OS generated by OC, specific types of physiological modulators are needed.

Metabolic and haemostatic effects of estradiol valerate/dienogest, a novel oral contraceptive: a randomized, open-label, single-centre study.

BACKGROUND AND OBJECTIVE: The hormonal components of combined oral contraceptives (COCs) have various metabolic and haemostatic effects. The objective of this study was to compare the metabolic and haemostatic effects of a novel COC comprising estradiol valerate/dienogest (E(2)V/DNG) with ethinylestradiol/levonorgestrel (EE/LNG). METHODS: In a randomized, open-label study conducted in Germany over seven cycles, healthy women aged 18-50 years received E(2)V/DNG (E(2)V 3 mg on days 1-2, E(2)V 2 mg/DNG 2 mg on days 3-7, E(2)V 2 mg/DNG 3 mg on days 8-24, E(2)V 1 mg on days 25-26, placebo on days 27-28; n = 30) or EE/LNG (EE 0.03 mg/LNG 0.05 mg on days 1-6, EE 0.04 mg/LNG 0.075 mg on days 7-11, EE 0.03 mg/LNG 0.125 mg on days 12-21, placebo on days 22-28; n = 28). The primary variables were the mean intraindividual relative changes from baseline to cycle 7 in high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol levels. Changes in other lipid parameters, haemostatic parameters, sex hormone-binding globulin (SHBG), cortisol-binding globulin (CBG), carbohydrate metabolism parameters, blood pressure and body weight were also assessed. RESULTS: Mean ± SD HDL cholesterol increased by 7.9% ± 21.8% with E(2)V/DNG and decreased by 2.3% ± 14.4% with EE/LNG. Mean ± SD LDL cholesterol decreased by 6.5% ± 15.9% with E(2)V/DNG and by 3.0% ± 17.4% with EE/LNG. Mean ± SD prothrombin fragment 1 + 2 and D-dimer levels remained essentially unchanged in the E(2)V/DNG group (-0.6% ± 30.3% and -2.1% ± 43.5%, respectively), but increased in the EE/LNG group (by 117.3% ± 358.0% and 62.9% ± 99.5%, respectively). Changes in other hepatic-induced parameters (SHBG, CBG) and carbohydrate metabolism were generally less pronounced with E(2)V/DNG versus EE/LNG. Body weight and blood pressure remained stable throughout the study in both treatment groups. Both formulations were well tolerated, with no serious adverse events reported. CONCLUSION: E(2)V/DNG had a minimal impact on metabolic and haemostatic parameters, and a more favourable effect than EE/LNG on lipid markers. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00185224.

Efectos beneficiosos no anticonceptivos de la píldora anticonceptiva / No disponible

El primer objetivo del uso de un anticonceptivo oral combinado (AOC) es el de evitar un embarazo. En ocasiones el AOC se asocia a efectos secundarios, pero cada día se conocen mejor los efectos beneficiosos no anticonceptivos del mismo. Existe evidencia de una buena calidad que asocia el uso de AOC con la mejoría de la dismenorrea, la disminución del sangrado menstrual y la mejoría del síndrome premenstrual. También se sabe que el uso de AOC protege frente a la enfermedad inflamatoria pélvica (EIP) y el embarazo ectópico, reduce la pérdida mineral ósea y es eficaz en el tratamiento del acné leve y moderado. Además, la AOC disminuye la incidencia de cáncer de ovario y cáncer de endometrio. Conocer estos efectos beneficiosos resulta de interés tanto para los profesionales sanitarios como para las mujeres (AU)

The first objective of using a combined oral contraceptive(COC) is that of avoiding pregnancy. COC is sometimes associated to side effects, but its non-contraceptive beneficial effects are becoming known day by day. There is evidence of the good quality associated to the use of COC with the improvement of dysmenorrhea, decrease of menstrual bleeding and improvement of premenstrual syndrome. It is also known that the use of COC protects against pelvic inflammatory disease (PID), and ectopic pregnancy, reduces bone mineral loss and is effective in the treatment of mild and moderate acne. Furthermore, COC decreases the incidence of ovarian cancer and endometrial cancer. Knowing these beneficial effects is of interest, both for the health care professionals and for women (AU)

St John's wort extract (Ze 117) does not alter the pharmacokinetics of a low-dose oral contraceptive.

PURPOSE: St John's wort (Hypericum perforatum) is an herbal remedy that is widely used in the treatment of depression. Recent clinical data have demonstrated that St John's wort extracts interfere with the action of various drugs and possibly also with combined oral contraceptives. Therefore, we investigated the effects of a St John's wort extract (Ze 117) with low hyperforin content on the pharmacokinetics of ethinylestradiol and 3-ketodesogestrel. METHOD: Sixteen healthy female volunteers, who had taken a low-dose oral contraceptive (Lovelle contains 0.02 mg ethinylestradiol + 0.15 mg desogestrel) for at least 3 months, participated in the study. Pharmacokinetic data (AUC, C(max), t(max)) were determined the day before (reference) and after (test) a 14-day period of Ze 117 intake (250 mg twice daily). RESULTS: Before the co-administration of Ze 117 on day 7, the geometric mean (geometric coefficient of variation) for the AUC(0-24) of ethinylestradiol was 152.53 pg.h/ml (87.39%) and after co-administration on day 21 it was 196.57 pg.h/ml (78.14%). The respective values for ketodesogestrel were 36.37 pg.h/ml (34.18%) and 41.12 pg.h/ml (34.36%). The mean of individual ratios (reference-to-test) of log-transformed AUC values (90% confidence interval) were 0.951 (0.915-0.986) for ethinylestradiol and 0.968 (0.944-0.992) for ketodesogestrel indicating a small gain [corrected] in bioavilability, but bioequivalence nevertheless. CONCLUSION: These results indicate that the recommended dose of the hypericum extract Ze117, which has a low hyperforin content, does not interact with the pharmacokinetics of the hormonal components of the low-dose oral contraceptive.

Drospirenone/ethinyl estradiol.

Drospirenone 3 mg/ethinyl estradiol 20 microg (24/4) is a new unique oral contraceptive formulation that combines in a novel dosing regimen the lowest dosage of ethinyl estradiol commonly used today with drospirenone, an innovative progestin. Drospirenone is a compound closely resembling progesterone, but with the antimineralocorticoid and antiandrogenic properties of a related therapeutic agent, the diuretic, antihypertensive and androgen receptor antagonist, 17alpha-spironolactone. The prolongation of hormonally active pills in the monthly drospirenone/ethinyl estradiol cycle from 21 days to 24 days, followed by 4 days of inactive pills, is an interesting variant of the recently developed extended pill regimens (1). Recent contraceptive research has focused on improving side effect profiles and providing noncontraceptive health and lifestyle advantages. Many of these benefits are now supported with evidence-based medicine (2). Most available oral contraceptives improve cycle regularity, menstrual pain, excessive menstrual flow and acne. However, weight gain, bloating, food cravings, breast tenderness and mood alterations (especially irritability and depression and the complex of affective, behavioral and somatic symptoms of premenstrual syndrome [PMS] and the severe form of PMS, premenstrual dysphoric disorder [PMDD]) are not generally improved with the traditional oral contraceptive formulations (3). Drospirenone/ethinyl estradiol 24/4 is currently the only hormonally based contraceptive regimen with large, randomized, controlled trials demonstrating efficacy for PMDD. It has received U.S. Food and Drug Administration (FDA) indications not only for the prevention of pregnancy but also for PMDD and for moderate acne vulgaris in women who choose oral contraception for birth control (4, 5).

Delivery of ethinylestradiol from film forming polymeric solutions across human epidermis in vitro and in vivo in pigs.

Film forming polymeric solutions may present an alternative to the common transdermal dosage forms such as patches or gels. To evaluate the potential of these systems for transdermal drug delivery the permeation of ethinylestradiol from four formulations with different polymers was tested across heat separated human epidermis. The formulation with the best results was then modified by incorporating chemical enhancers to further increase the efficiency of the delivery system. Finally, drug delivery from the developed film forming systems was compared to a commercially available transdermal patch in vitro as well as in vivo in pigs. Among the tested preparations the formulation with polyurethane-14-AMP-acrylates copolymer (DynamX) showed the highest ethinylestradiol permeation. The drug transport was further increased with the incorporation of oleic acid as penetration enhancer, especially when used in combination with propylene glycol. The enhancing effect of oleic acid/propylene glycol was concentration-dependent and increased disproportionately with rising enhancer content. The film forming solution showed a higher ethinylestradiol permeation through heat separated human epidermis than the commercial EVRA patch in vitro and achieved measurable plasma concentrations of ethinylestradiol in vivo in pigs. These promising results encourage the further development of film forming polymeric solutions as novel transdermal dosage form.

Alcohol elimination at low blood concentrations among women taking combined oral contraceptives.

OBJECTIVE: Evidence implicating a role of natural and synthetic estrogens and/or progestin on ethanol pharmacokinetics can be traced back to the mid-1970s when reports of large metabolic differences were found suggesting that sex hormones interfered with the efficient clearance of alcohol at the liver microsomal level. Research teams in this area manipulate sex hormone levels by either examining natural-cycling women at different phases of their menstrual cycle or others taking oral contraceptives that synthetically regulate the hormonal fluctuations. These collective studies (over a dozen to date involving over 200 participants) have all been similar in focus and outcome. With one important exception, the published laboratory research since 1976 has failed to replicate the earliest research suggesting sex hormone effects. One well-controlled study in 1987 did generate renewed interest in the area with the paradoxical finding that progesterone actually enhanced alcohol elimination at low blood concentrations (<.025%). The present study represented the most direct attempt to replicate this particular finding using 5-minute breath alcohol readings that extended below blood alcohol concentrations of .025%. METHOD: A total of 17 women taking combined oral contraceptives were tested during both menstruation and the luteal phase (Days 16-22) of their cycle in counterbalanced sequence. RESULTS: Pharmacokinetics differences were not found. CONCLUSION: These results contribute further to a literature base demonstrating the limited effects of both natural and synthetic sex hormones on alcohol metabolism in women.

The interaction between St John's wort and an oral contraceptive.

OBJECTIVES: The popular herbal remedy St John's wort is an inducer of cytochrome P450 (CYP) 3A enzymes and may reduce the efficacy of oral contraceptives. Therefore we evaluated the effect of St John's wort on the disposition and efficacy of Ortho-Novum 1/35 (Ortho-McNeil Pharmaceutical, Inc, Raritan, NJ), a popular combination oral contraceptive pill containing ethinyl estradiol (INN, ethinylestradiol) and norethindrone (INN, norethisterone). METHODS: Twelve healthy premenopausal women who were using oral contraception (>3 months) received a combination oral contraceptive pill (Ortho-Novum 1/35) for 3 consecutive 28-day menstrual cycles. During the second and third cycles, the participants received 300 mg St John's wort 3 times a day. The serum concentrations of ethinyl estradiol (day 7), norethindrone (day 7), follicle-stimulating hormone (days 12-16), luteinizing hormone (days 12-16), progesterone (day 21), and intravenous and oral midazolam (days 22 and 23) were determined in serial blood samples. The incidence of breakthrough bleeding was quantified during the first and third cycles. RESULTS: Concomitant use of St John's wort was associated with a significant (P <.05) increase in the oral clearance of norethindrone (8.2 +/- 2.7 L/h to 9.5 +/- 3.4 L/h, P =.042) and a significant reduction in the half-life of ethinyl estradiol (23.4 +/- 19.5 hours to 12.2 +/- 7.1 hours, P =.023). The oral clearance of midazolam was significantly increased (109.2 +/- 47.9 L/h to 166.7 +/- 81.3 L/h, P =.007) during St John's wort administration, but the systemic clearance of midazolam was unchanged (37.7 +/- 11.3 L/h to 39.0 +/- 10.3 L/h, P =.567). Serum concentrations of follicle-stimulating hormone, luteinizing hormone, and progesterone were not significantly affected by St John's wort dosing (P >.05). Breakthrough bleeding occurred in 2 of 12 women in the control phase compared with 7 of 12 women in the St John's wort phase. The oral clearance of midazolam after St John's wort dosing was greater in women who had breakthrough bleeding (215.9 +/- 66.5 L/h) than in those who did not (97.5 +/- 37.2 L/h) (P =.005). CONCLUSION: St John's wort causes an induction of ethinyl estradiol-norethindrone metabolism consistent with increased CYP3A activity. Women taking oral contraceptive pills should be counseled to expect breakthrough bleeding and should consider adding a barrier method of contraception when consuming St Johns wort.

Characterization of immunoglobulins and cytokines in human cervical mucus: influence of exogenous and endogenous hormones.

Mucosal immunity in the female reproductive tract is influenced by immunoglobulins (Igs), cytokines, and reproductive hormones. Previous studies of reproductive-aged women demonstrated that IgA and IgG increases in cervical mucus corresponded to elevated levels of IL-1beta which occurred 1 day before the peak of endogenous estradiol production prior to ovulation. We sought to determine the effect of exogenous hormones on reproductive tract immunity in women on oral contraceptive pills (OCPs) and to compare the results with respect to naturally cycling women. Twelve women of reproductive age who had negative cervical cultures, a normal pap smear, and agreed to abstain from sexual intercourse during the study initiated OCPs. Cervical mucus and vaginal washes were collected at six intervals (2-3 days apart) throughout the treatment cycle. Fifteen naturally cycling women had similar samples collected prior to, during, and subsequent to ovulation. Cervical mucus samples were assayed for IgA, IgG, IL-1beta, IL-6, and IL-10 by enzyme-linked immunosorbent assay (ELISA). IgA, IgG and IL-1beta levels in women on OCPs paralleled increasing levels of norethindrone. Mean values of IgA increased from a low of 14.4+/-3.1 to 41.1+/-9.4 mg/dl and decreased significantly after the cessation of the pills (P < 0.001). In naturally cycling women, the largest quantities of Igs were detected prior to ovulation. By comparison, mean values of IgA in the cervical mucus of women on OCPs (24.4 mg/dl) exceeded peak levels of IgA in the cervical mucus of naturally cycling women (14.6 mg/dl). IgA was the predominant Ig detected in cervical mucus of women on OCPs. Both immunoglobulins in each group exhibited changes relative to their hormonal status. The increased levels of IgA in the cervical mucus of women on OCPs may explain the clinical observation of a lower incidence of sexually transmitted diseases.

Modification of plasma insulin-like growth factors and binding proteins during oral contraceptive use and the normal menstrual cycle.

OBJECTIVE: Sex steroid regulation of the insulin-like growth factor axis is a subject of contention. We examined the effect of combined oral contraceptives and investigated the cyclic variations in the insulin-like growth factor axis. STUDY DESIGN: Fasting blood samples were taken from 9 women receiving oral contraceptives, 10 women receiving no medication, and 10 male subjects. RESULTS: In women receiving oral contraceptives, insulin-like growth factor binding protein 1 remained highly phosphorylated and levels were acutely increased by sex steroid treatment (305 +/- 110 microg/L on day 14 of the cycle [medication phase] vs 118 +/- 70 microg/L during the medication-free period, P <.03). In women receiving no medication, insulin-like growth factor binding protein 1 levels were significantly lower (69 +/- 50 microg/L on day 14 of the menstrual cycle, P <.001) and varied cyclically, with a rise in the late-secretory phase that coincided with the appearance of nonphosphorylated and less phosphorylated insulin-like growth factor binding protein 1 isoforms. Compared with those in untreated women and in men, insulin-like growth factor I levels were decreased in women receiving oral contraceptives (405 +/- 104 ng/mL in untreated women and 330 +/- 28 ng/mL in men vs 287 +/- 73 ng/mL in women receiving oral contraceptives, P <.004). Oral contraceptive use had no effect on insulin-like growth factor II levels, and neither insulin-like growth factor I nor insulin-like growth factor II showed cyclic variation. CONCLUSION: The bioavailability of insulin-like growth factor I is reduced in users of oral contraceptives. This may contribute to the metabolic changes observed in such subjects.

New once-a-month injectable contraceptives, with particular reference to Cyclofem/Cyclo-Provera.

Once-a-month injectable contraceptives containing a progestogen and an estrogen have been developed that disrupt vaginal bleeding patterns less than the widely used progestogen-only preparations. Pharmacokinetic studies were undertaken of dosages and ratios of the progestogens and the respective estrogens. In Phase III clinical trials, annual pregnancy rates were below 0.4% for Mesigyna (norethisterone enanthate/estradiol valerate, Schering AG, Berlin, Germany) and below 0.2% for Cyclofem (MPA/E2C) (medroxyprogesterone acetate/estradiol cypionate, Aplicaciones Farmaceuticas, SA, Mexico and PT Tunggal, Indonesia). More than two-thirds of women had predictable, regular cycles, and discontinuation due to bleeding-related problems occurred less than half as often as with progestogen-only injectables. With MPA/E2C, return to fertility is similar to that observed with other hormonal or intrauterine methods, and both products have little effect on lipids or hemostasis. Introductory trials of MPA/E2C in 12000 women with 100000 woman-months of experience confirmed the high efficacy of the product in routine use. The use of MPA/E2C in a non-reusable injection device, Uniject (Becton Dickinson, Franklin Lakes, NJ) is discussed. Once-a-month hormonal contraceptives have been shown to provide a safe contraceptive option for all women and an alternative for women who wish to use injectable formulations that cause less disruption in vaginal bleeding and minimal side effects.