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Objective To compare medroxyprogesterone acetate (MPA) concentrations between HIV-positive women on antiretroviral therapy (ART) and HIV-negative women initiating depot medroxyprogesterone (DMPA) injectable. Study design Secondary analysis of 28 HIV-positive women on non-nucleoside reverse transcriptase inhibitor-containing ART regimens and 10 HIV-negative women randomized to initiate DMPA in a clinical trial of progestin contraception in Malawi. Results MPA concentrations were significantly lower among HIV-positive women on ART, compared with HIV-negative women, at week 4 and week 13 (p=.03 for both), but not at day 3 or week 26 post-DMPA initiation. Conclusions Antiretroviral medications may affect MPA metabolism in HIV-positive African women.

OBJECTIVE: To assess the pharmacokinetics (PK) of levonorgestrel after 1.5 mg oral doses (LNGEC) in women with normal, obese and extremely obese body mass index (BMI). STUDY DESIGN: The 1.5 mg LNG dose was given to healthy, reproductive-age, ovulatory women with normal BMI (mean 22.0), obese (mean 34.4), and extremely obese (mean 46.6 kg/m(2)) BMI. Total serum LNG was measured over 0 to 96 hours by radioimmunoassay while free and bioavailable LNG were calculated. The maximum concentration (Cmax), time to maximum concentration (Tmax), and area under the curve (AUC) of LNG were assessed. Pharmacokinetic parameters calculated included half-life (t1/2), clearance (CL) and volume of distribution (Vss). RESULTS: Ten normal-BMI, 11 obese-BMI, 5 extremely obese-BMI women were studied. After LNG-EC, mean total LNG metrics were lower in the obese and extremely obese groups compared to normal (Cmax 10.5 and 10.5 versus 16.2 ng/mL, both p

Objective The objective was to assess the extent of concordance between self-reported contraceptive use and the presence of contraceptive progestins in serum. Study design We evaluated self-reported contraceptive use by using radioimmunoassay to examine baseline serum levels of medroxyprogesterone acetate (MPA) and levonorgestrel (LNG) among 97 Malawian women enrolling in a contraceptive trial. Results Twelve percent (12/97) of study participants who reported no hormonal contraceptive use in the previous 6 months had either MPA or LNG detected in their serum. Conclusions The observed discordance between self-report and detection of exogenous hormones in serum indicates that caution is warranted when drawing conclusions based on self-reported contraceptive use.

Objective To assess the pharmacokinetics of combined oral contraceptive (COC) components and prevalence of ovulation in HIV-positive women using ritonavir-containing antiretroviral regimens compared to those using regimens previously found not to interact with COCs or not using any antiretrovirals. Study design We conducted a prospective cohort pharmacokinetic pilot study comparing the pharmacokinetics of levonorgestrel (LNG) and ethinyl estradiol (EE) in HIV-positive women taking ritonavir-containing antiretroviral regimens to those in women using non-ritonavir-containing regimens or no antiretrovirals. Participants received COCs containing LNG/EE 150/30 mcg for 21 days. Beginning day 21, we collected serial blood samples over 72 h. The primary outcome was area under the curve (AUC) of LNG, with secondary outcomes including other LNG pharmacokinetic measures, EE pharmacokinetics and ovulation as measured by serum progesterone. Results Pharmacokinetic parameters of LNG showed a trend toward increased exposure in women on ritonavir. LNG AUClast increased by 32.6% (312±60.9 vs. 243±82.6 ng/mL*h, p=.033, n=5) in women taking ritonavir compared to the control group (n=10). The Cmax (9.68±1.81 vs. 7.62±2.29 ng/mL) and Cmin (4.97±1.15 vs. 3.70±1.29 ng/mL) were also higher in the ritonavir arm. After excluding the inconsistent users (n=2), CL of LNG was reduced in the ritonavir arm (p=.032). EE pharmacokinetic profiles were not different between groups. The progesterone concentrations were similar in women of both groups, and none were consistent with ovulation during the treatment cycle. Conclusion Women on ritonavir showed an approximately 30% increase in LNG exposure but no difference in EE exposure. Implications The current data suggest that ritonavir does not have a clinically significant impact on oral contraceptive pharmacokinetics.

Objective This study examines the effect of a progestogen (depot-medroxyprogesterone acetate, DMPA) on resting metabolic rate (RMR) in a cohort of young, normal-weight healthy women. We hypothesize an increase in RMR and nonshivering thermogenesis (NST) resulting in increased body temperature by DMPA. Study design We performed a prospective cohort study in 13 subjects tested at baseline, 3 weeks and 9 weeks after 150 mg intramuscular DMPA administration. RMR was determined with indirect calorimetry. Secondary endpoints included changes in body mass index (BMI), body composition, temperature and serum levels of estradiol (E2), luteinizing hormone (LH), progesterone and MPA. Results The percent change in RMR from baseline to week 3 (9%) was significantly higher than the percent change from baseline to week 9 (1.6%) (p = .045). The greatest percent change from baseline to week 3 compared to baseline to week 9 was seen in women initiating DMPA in the luteal phase of the cycle. Hypothalamic-pituitary-ovarian axis was evident by decreases in E2, LH and progesterone. DMPA resulted in increased body temperature with a significant correlation between the change in body temperature and the change in RMR. No change in body composition was seen. Conclusions RMR and NST increased in young healthy women with normal BMI 3 weeks after receiving the initial dose of 150 mg DMPA for contraception. The effect was augmented when the drug was administered during the luteal phase of the menstrual cycle. Implication DMPA increases RMR and thermogenesis independent of changes in body mass. An increase in weight with chronic DMPA may result from a combination of hyperphagia and abnormal NST in predisposed individuals.

Objective To measure breast tissue and serum LNG concentrations in women using a LNG-IUS. Study design This pilot study was performed in 25 healthy women undergoing breast surgery at the Ghent University hospital. LNG concentrations were measured in serum and microdissected breast tissue samples using a validated ultra-performance liquid chromatography/tandem mass spectrometry assay. Result(s) The mean LNG concentration in the 18 LNG-IUS users was 0.18±0.16 ng/mL in serum and 0.26±0.28 ng/g in breast tissue. For four women without any form of hormonal contraceptive (the negative controls), the mean concentrations were below the limit of quantification, i.e., 0.15 ng/mL and 0.20 ng/g, for serum and breast tissue, respectively. For the three positive controls the concentrations in the serum (20.5 and 3.4 ng/ml) and the breast (3.74 and 1.24 ng/g) were respectively for the 20 μg EE/100 μg users and 315 pg/ml in the serum and 1.17 ng/g in the breast for the minipill user. The intracellular free fraction of LNG may be as low as 0.008 ng/g. Conclusion(s) The concentration of LNG in breast epithelium cells in women using the LNG-IUS is very low. Implications The relationship between the serum and breast tissue levels of LNG was studied in women using a LNG-IUS or oral LNG-containing contraception. Compared to oral contraception, the tissue levels of LNG in LNG-IUS users are much lower in the breast. It is not known what level of LNG exposure in the breast would stimulate RANKL and WNT4 expression; such information is needed.

OBJECTIVES: To evaluate the pharmacokinetics (PK) of levonorgestrel-containing combined oral contraceptives (COCs) in obese women. STUDY DESIGN: We pooled and reanalyzed data from 89 women with different BMI categories from four clinical studies. The levonorgestrel (LNG) and ethinyl estradiol (EE) PK were analyzed utilizing a zero-order absorption (K(0)), two-compartment PK model to evaluate key PK parameters in relation to a range of weights, body mass index (BMI), and body surface area (BSA). RESULTS: Increasing of body habitus metrics are correlated with decreasing C(max) (p

Pharmacokinetics of norethindrone in combination oral contraceptive regimen are well described among HIV+ women treated with ritonavir-boosted protease inhibitor therapies; however, such characterization is lacking in women using progestin-only contraception. Our objective is to characterize pharmacokinetics of norethindrone in HIV+ women using ritonavir-boosted atazanavir treatment during progestin-only contraceptive regimens.An open-label, prospective, nonrandomized trial to characterize the pharmacokinetics of norethindrone in HIV+ women receiving ritonavir-boosted atazanavir (n=10; treatment group) and other antiretroviral therapy known to not alter norethindrone levels (n=17; control group) was conducted. Following informed consent, women were instructed to take a single daily fixed oral dose of 0.35 mg norethindrone and 300 mg/100 mg atazanavir/ritonavir for 22 days. On day 22, serial blood samples were collected by venous catheter at 0, 1, 2, 3, 4, 6, 8, 12, 24, 48 and 72 h. Whole blood was processed to collect serum and stored at -20°C until later analysis using radioimmunoassay. Pharmacokinetic parameters were estimated using noncompartmental method.In the treatment group, compared to the control group, an increase in area under the curve₀₋₂₄ (16.69 h*ng/mL vs. 25.20 h*ng/mL; p.05) and maximum serum concentration (2.09 ng/mL vs. 3.19 ng/mL; p.05), decrease (25%-40%) in apparent volume of distribution and apparent clearance, and unaltered half-life were observed.Our findings suggest that progestin-only contraceptives, unlike combination oral contraceptives, benefit from drug-drug interaction and achieve higher levels of exposure. Further studies are needed to establish whether pharmacokinetic interaction leads to favorable clinical outcomes.Norethindrone-based progestin-only contraceptives, unlike combination oral contraceptives, exhibit greater drug exposure when co-administered with ritonavir-boosted atazanavir regimen and thus may not warrant a category 3 designation by the World Health Organization. Prospective studies are needed to confirm whether pharmacokinetic interaction results in favorable clinical outcomes.

To determine if increasing the hormone dose or eliminating the hormone-free interval improves key pharmacokinetic (PK) alterations caused by obesity during oral contraceptive (OC) use.Obese [body mass index (BMI)≥30 kg/m(2)], ovulatory, otherwise healthy, women received an OC containing 20 mcg ethinyl estradiol (EE)/100 mcg levonorgestrel (LNG) dosed cyclically (21 days active pills with 7-day placebo week) for two cycles and then were randomized for two additional cycles to the following: continuous cycling (CC, a dose neutral arm using the same OC with no hormone-free interval) or increased dose (ID, a dose escalation arm using an OC containing 30 mcg EE/150 mcg LNG cyclically). During Cycles 2, 3 and 4, outpatient visits were performed to assess maximum serum concentration (Cmax), area under the curve (AUC0-∞) and time to steady state as well as pharmacodynamics. These key PK parameters were calculated and compared within groups between baseline and treatment cycles.A total of 31 women enrolled and completed the study (CC group, n=16; ID group, n=15). Demographics were similar between groups [mean BMI: CC, 38 kg/m(2) (S.D. 5.1); ID, 41 kg/m(2) (S.D. 7.6)]. At baseline, the key LNG PK parameters were no different between groups; average time to reach steady state was 12 days in both groups; Cmax were CC: 3.82±1.28 ng/mL and ID: 3.13±0.87 ng/mL; and AUC0-∞ were CC: 267±115 h ng/mL and ID: 199±75 h ng/mL. Following randomization, the CC group maintained steady-state serum levels whereas the ID group had a significantly higher Cmax (p.001) but again required 12 days to achieve steady state. However, AUC was not significantly different between CC (412±255 h ng/mL) and ID (283±130 h ng/mL). Forty-five percent (14/31) of the study population had evidence of an active follicle-like structure prior to randomization and afterwards this decreased to 9% (3/31).Both increasing the OC dose and continuous dosing appear to counteract the impact of obesity on key OC PK parameters.Obesity adversely affects the pharmacokinetics of very low dose OC pills. Although the impact of these changes on OC efficacy is still under debate, PK parameters can be normalized in obese users by continuous dosing or increasing to a low-dose pill.

Background The metabolic effects of progestin-only long-acting reversible contraception [levonorgestrel-releasing intrauterine system (LNG-IUS) and etonogestrel implant (ENG-I)] have been studied in normal-weight women but not in obese [body mass index≥30kg/m2] women. Study Design A nonrandomized open-label prospective trial of healthy obese, reproductive-age women desiring to use long-acting reversible contraception (LARC) or nonhormonal contraception (NHC). At baseline, 3 months and 6 months, homeostasis model assessment insulin resistant (HOMA-IR) score, insulin sensitivity (HOMA-%S) and β-cell function (HOMA-%B) were calculated based on fasting insulin and glucose values. In addition, components of metabolic syndrome [fasting glucose (FG), high density lipoprotein cholesterol and triglycerides, systolic and diastolic blood pressure, abdominal circumference] were measured. Twenty-four subjects total (8 in each arm) were needed to detect a 1.0 difference in HOMA-IR with 80% power and a two-sided alpha of 0.05. Results We present data on eight NHC, eight ENG-I and nine levonorgestrel intrauterine system (LNG-IUS) users. FG increased, and insulin sensitivity decreased over time among ENG-I users to a greater extent than among LNG-IUS users when compared to women using a nonhormonal method [FG change over 6 months=9.4mg/dL, 4.6mg/dL and − 2.1mg/dL, respectively; p=.01); (HOMA-%S change over 6 months=−29.9%, − 14.8% and 19.3%, respectively; p=.02)], while β-cell function and insulin resistance did not change significantly (p>.05). Conclusion While changes in FG and insulin sensitivity were seen in the present study among obese progestin-only contraceptive users, either progestin-only LARC method may be safely used clinically.

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.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.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).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.

Background The effect of obesity on ovarian follicular suppression in women using low-estrogen dose contraceptive patches has not been determined. Study Design A Phase II, parallel-group, multicenter, three-cycle study evaluated three patches containing different ethinyl estradiol (EE) and levonorgestrel (LNG) doses. Serum levels of EE, LNG, sex hormone-binding globulin and progesterone were compared in 41 obese [body mass index (BMI) ≥ 30] and 75 nonobese (BMI Results Suppression of ovulation during the luteal phase was dose dependent, with the highest dose (AG200-15) preventing progesterone increases in all women (cycles 2–3). In the follicular phase, the lowest-dose patch had the highest rate of increased progesterone in nonobese subjects. Progesterone levels ≥ 3.0 ng/mL in the follicular phase were more common in obese than nonobese women. Conclusions AG200-15 suppresses ovulation in obese and nonobese women. All three patches found increased progesterone in the follicular phase, albeit more in obese versus nonobese women.

Background This study compares the pharmacokinetic profile, adhesion and safety of the AG200-15 Agile Patch (AP), a novel contraceptive patch releasing low-dose ethinyl estradiol (EE) and levonorgestrel (LNG), during wear under external conditions of heat, humidity and exercise versus normal activities. Study Design This open-label, three-period, five-treatment, crossover study randomized 24 healthy women to one of six external condition sequences. Each sequence included one normal wear and two external conditions periods. Participants wore the AP for 7 days under normal conditions or conditions of daily sauna, treadmill, whirlpool or cool water immersion, with a 7-day washout between treatments. Blood samples were collected for pharmacokinetic evaluations. Results Twenty-four subjects completed the study. For EE, the mean maximum concentration level ( C max ), area under the plasma concentration���time curve from time 0 to 168 h (AUC 0���168 ) and area under the plasma concentration���time curve from time 0 to infinity (AUC 0���inf ) were higher during normal conditions compared with all external conditions (geometric means ratio range: 80%���93%), except cool water. Mean steady-state concentrations ( C ss ) of EE were highest under normal conditions, followed by cool water, sauna, whirlpool and treadmill. The LNG mean C max , AUC 0���168 , AUC 0���inf and C ss were higher under normal wear versus all other conditions (geometric means ratios: 75%���82%), with the exception of AUC 0���168 , AUC 0���inf and C ss for cold water. Median times to maximum concentration ( T max ) for EE and LNG were comparable across conditions. Patch adhesion was excellent under all conditions. Adverse events were mild, with none serious or leading to discontinuation. Conclusions Although slightly lower mean drug concentration levels were observed for whirlpool, treadmill and sauna, drug concentrations under all conditions were well within therapeutic ranges established for the AP during normal wear and within ranges reported for low-dose combination oral contraceptives. Patch adhesion was excellent; the AP was safe and well tolerated under all conditions.

Background Pharmacokinetic (PK) parameters based on short sampling times (48 h or less) may contain inaccuracies due to their dependency on extrapolated values. This study was designed to measure PK parameters with greater accuracy in obese users of a low-dose oral contraceptive (OC) and to correlate drug levels with assessments of end-organ activity. Study Design Obese [body mass index (BMI) ���30 kg/m 2 ], ovulatory, otherwise healthy women ( n =32) received an OC containing 20 mcg ethinyl estradiol (EE)/100 mcg levonorgestrel (LNG) for two cycles. EE and LNG PK parameters were characterized for 168 h at the end of Cycle 1. During Cycle 2, biweekly outpatient visits were performed to assess cervical mucus, monitor ovarian activity with transvaginal ultrasound and obtain serum samples to measure EE, LNG, estradiol and progesterone levels. PK parameters were calculated and correlated with end-organ activity and compared against control samples obtained from normal and obese women sampled up to 48 h in a previous study. Standard determination of PK accuracy was performed, defined by the dependency on extrapolated values (���excess��� area under the curve of 25% or less). Results The mean BMI was 39.4 kg/m 2 (SD 6.6) with a range of 30���64 kg/m 2 . Key LNG PK parameters were as follows: clearance, 0.52 L/h (SD 0.24); half-life, 65 h (SD 40); area under the curve (AUC), 232 h*ng/mL (SD 102); and time to reach steady state, 13.6 days (SD 8.4). The majority of subjects had increased ovarian activity with diameter of follicles ���8 mm ( n =25), but only seven women had follicles ���10 mm plus cervical mucus scores ���5. Evidence of poor end-organ suppression did not correlate with the severity of the alterations in PK. As compared to historical normal and obese controls (48-h PK sampling), clearance, half-life, AUC and time to reach steady state were found to be significantly different (p���.05) in obese women undergoing a longer duration of PK sampling (168 h). Longer sampling also improved PK accuracy for obese women (excess AUC 20%) as compared to both normal and obese controls undergoing shorter sampling times (48 h) with excess AUCs of 25% and 50%, respectively. Conclusions Obesity results in significant alterations in OC steroid PK parameters, but the severity of these alterations did not correlate with end-organ suppression. A longer PK sampling interval (168 h vs. 48 h) improved the accuracy of PK testing.

Background: The effects of subcutaneous depo-medroxyprogesterone acetate (DMPA-SC) injection on androgenic markers in obese women have not previously been studied. Study Design: Five normal-weight [body mass index (BMI)=18.5–24.9 kg/m 2 ], five obese (BMI=30–39.9 kg/m 2 ) and five extremely obese (BMI≥40 kg/m 2 ) women were recruited for this prospective experimental study in which 104 mg DMPA-SC was administered at baseline and 12 weeks later. Serum levels of total testosterone (T), androstenedione (A), dehydroepiandrosterone sulfate (DHEAS), 3α-androstanediol glucuronide and sex hormone-binding globulin (SHBG) were quantified by immunoassay methods at baseline and at 13 and 26 weeks following the first injection; free T was calculated. Results: At baseline, obese women had lower levels of A and SHBG and higher total and free T levels than normal-weight women. There were a statistically significant decrease in the levels from baseline to week 26 among all three BMI classes for A, total T and SHBG (p≤.03) and an increase from baseline to week 26 in weight (p=.02). In addition, there was a statistically significant decrease in DHEAS from baseline to week 13 among all three BMI classes (p=.01), which was not sustained at week 26 (pN.1). Overall, the three groups responded similarly to all changes at week 13, and there were no statistically significant differences between groups at any time point (p≥.06). Conclusion: DMPA-SC use in normal-weight, obese and extremely obese women can decrease serum androgen markers.

Background This study evaluated the ethinyl estradiol (EE) and levonorgestrel (LNG) pharmacokinetic profiles of AG200-15, a transdermal contraceptive delivery system, compared with a combination oral contraceptive (COC) containing EE 35 mcg and norgestimate 250 mcg. Study design A Phase 1, open-label, single-center study in 36 healthy women was conducted over three cycles with a randomized crossover design. After a run-in cycle of 21 days on and 7 days off with AG200-15, participants were randomized to receive one of two treatments: a 21/7-day cycle of AG200-15 either followed or preceded by one cycle of the COC. This trial is registered on ClinicalTrials.gov under the identifier NCT01243580. Results During the third week of AG200-15 use, mean (��standard deviation) maximum serum concentration ( C max ), area under the curve 0���168 h and steady-state concentration ( C ss48���168 h ) for EE were 51.3��17.3 pg/mL, 6.26��2.46 ng h/mL and 35.7��14.5 pg/mL, respectively; for LNG, the corresponding values were 2400��1140 pg/mL, 317��159 ng h/mL and 1847��930 pg/mL, respectively. The AG200-15 EE C max was approximately 60% lower and the EE C ss was 15%���20% lower than those obtained with the COC. The calculated daily dose of AG200-15 was equivalent to a 30-mcg EE COC. The most common adverse events (AEs; >10%) in the AG200-15 group were headache, nausea and application-site irritation. All drug-related AEs were mild, and no serious AEs were reported. Conclusions EE and LNG daily exposure during AG200-15 treatment was within the range reported for a low-dose COC. The daily EE dose with AG 200-15 was equivalent to a 30-mcg COC and was safe and well tolerated.

Objective The objective was to investigate changes in luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol (E 2 ) and progesterone (P) during the hormone-free interval (HFI) of 6 combined oral contraceptives (COCs). Design Blood samples were obtained from 62 women. Results When COCs were grouped by ethinyl estradiol (EE) dose, there was a significant positive mean slope for LH and FSH during the HFI for the 30- and 35 mcg-EE doses, whereas 20 showed a gradual nonsignificant slope. All E 2 slopes were significant. P remained suppressed with all doses. Conclusion A more rapid rebound of gonadotropin levels is found with higher doses of EE during the HFI. Implications This study showed a more rapid rebound of pituitary hormone levels among women using higher-EE-dosage formulations, which was demonstrated by the statistically significant slope for mean LH and FSH from day 1 to day 7 of the HFI. The degree of suppression did not vary across progestin generations. It remains to be established whether women who experience side effects during their HFI may benefit from using a COC with a lower EE dose to minimize changes in endogenous pituitary hormone levels.

This study was conducted to compare oral contraceptive (OC) pharmacokinetics (PK) in normal-weight [body mass index (BMI) 19.0-24.9] and obese (BMI 30.0-39.9) women.During the third week of the third cycle of OC use, we admitted 15 normal-weight and 15 obese women for collection of 12 venous specimens over 24 h. Using radioimmunoassay techniques, we measured levels of ethinyl estradiol (EE) and levonorgestrel (LNG). During the same cycle, women underwent twice-weekly sonography to assess ovarian follicular development and blood draws to measure endogenous estradiol (E2) and progesterone levels.Obese women had a lower area under the curve (AUC; 1077.2 vs. 1413.7 pg*h/mL) and lower maximum values (85.7 vs. 129.5 pg/mL) for EE than normal-weight women (p=.04 and0.01, respectively); EE trough levels were similar between BMI groups. The similar, but smaller, differences in their LNG levels for AUC and maximum values (C(max)) were not statistically significant. While peak values differed somewhat, the LNG trough levels were similar for obese and normal-weight women (2.6 and 2.5 ng/mL, respectively). Women with greater EE AUC had smaller follicular diameters (p=.05) and lower E2 levels (p=.04). While follicular diameters tended to be larger among obese women, these differences were not statistically significant.OC hormone peak levels are lower among obese women compared to normal-weight women, but their trough levels are similar. In this small study, the observed PK differences did not translate into more ovarian follicular activity among obese OC users.

The realities of the EE and progestin pharmacokinetics described in this commentary imply that there should be less fixation on using the lowest dose oral contraceptive available and more flexibility in adjusting the OC regimen. These pharmacokinetic phenomena of individual variability (and individual response) are equally relevant to the issue of postmenopausal hormone replacement therapy since the same classes of drugs are involved. (excerpt)

The primary objective is to examine activation of food motivation centers in the brain before and 8 weeks after depo medroxyprogesterone acetate (DMPA) administration.This prospective experimental pilot study examined the effects of DMPA on food motivation centers utilizing functional magnetic resonance imaging (fMRI) in eight nonobese, ovulatory subjects. fMRI blood oxygen level dependent (BOLD) signal was measured using a 3-Tesla Scanner while participants viewed images of high-calorie foods, low-calorie foods and nonfood objects. fMRI scans were performed at baseline and 8 weeks after participants received one intramuscular dose of DMPA 150 mg. fMRI data were analyzed using the FMRIB Software Library. Changes in adiposity and circulating leptin and ghrelin levels were also measured.There was a greater BOLD signal response to food cues in brain regions associated with food motivation (anterior cingulate gyrus, orbitofrontal cortex) 8 weeks after DMPA administration compared to baseline (z2.3, p.05 whole-brain analysis clustered corrected). No statistically significant change was detected in circulating leptin or ghrelin levels or fat mass 8 weeks after DMPA administration.Analysis of differences in food motivation may guide the development of interventions to prevent weight gain in DMPA users.These data support a neural origin as one of the mechanisms underlying weight gain in DMPA users and may guide future research examining weight gain and contraception.

Background St. John's wort (SJW), a commonly used herbal remedy, has been shown to compromise the efficacy of drugs, including oral contraceptive pills (OCPs), by inducing cytochrome P-450. We investigated whether the simultaneous use of SJW with OCPs resulted in elevated serum androgen levels with implications of impaired OCP treatment of hirsutism and acne. Materials and Methods Fifteen healthy women were treated with the low-dose OC Loestrin 1/20™ for 2 months and then additionally with SJW for 2 months. Androgen and sex hormone-binding globulin (SHBG) levels were measured in serum by immunoassay methods; free testosterone (fT) was calculated. Results were analyzed using the Wilcoxon signed-rank test. Results There were no statistically significant differences in androgen levels after the addition of SJW in women using Loestrin 1/20™. However, there were decreases in total testosterone and fT levels (10.7% and 15.8%, respectively) along with a small increase in SHBG levels (7.0%). Conclusions In women using OCPs and SJW simultaneously, it appears that SJW does not interfere with the antiandrogenic properties of OCPs.

Oral contraceptives (OC) suppress excess androgen production; however, different progestins in combination with low-dose estrogens produce divergent effects on sex hormone-binding globulin (SHBG) and testosterone that may influence clinical outcomes. This multicenter, open-label, randomized study compared biochemical androgen profiles and clinical outcomes associated with two OC containing the same amounts of ethinyl estradiol (EE, 20 micrograms) but different progestins, levonorgestrel (LNG, 100 micrograms), and norethindrone acetate (NETA, 1000 micrograms). Fifty-eight healthy women (18-28 years old) received three cycles of treatment with LNG/EE (n = 30) or NETA/EE (n = 28). The results showed that LNG reduced androgen levels in three compartments--adrenal, ovarian, and peripheral. NETA reduced only adrenal and peripheral androgens. Despite a 2.2-fold greater relative increase in SHBG with NETA than LNG, bioavailable testosterone (T) was reduced by the same amount with LNG and NETA. Both treatments improved acne and were well tolerated. Low-dose OC (EE, 20 micrograms) are effective in reducing circulating androgens and acne lesions without causing weight gain. Although LNG and NETA affected secondary markers differently, both OC formulations produced an equivalent decrease in bioavailable.Oral contraceptives (OCs) suppress excess androgen production; however, different progestins in combination with low-dose estrogens produce divergent effects on sex hormone-binding globulin (SHBG) and testosterone that may influence clinical outcomes. This multicenter, open-label, randomized study compared biochemical androgen profiles and clinical outcomes associated with 2 OCs containing the same amounts of ethinyl estradiol (EE, 20 mcg) but different progestins, levonorgestrel (LNG, 100 mcg), and norethindrone acetate (NETA, 1000 mcg). 58 healthy women aged 18-28 years received 3 cycles of treatment with LNG/EE (n = 30) or NETA/EE (n = 28). The results showed that LNG reduced androgen levels in 3 compartments-adrenal, ovarian, and peripheral. NETA reduced only adrenal and peripheral androgens. Despite a 2.2-fold greater relative increase in SHBG with NETA than LNG, bioavailable testosterone (T) was reduced by the same amount with LNG and NETA. Both treatments improved acne and were well tolerated. Low-dose OC (EE, 20 mcg) are effective in reducing circulating androgens and acne lesions without causing weight gain. Although LNG and NETA affected secondary markers differently, both OC formulations produced an equivalent decrease in bioavailable T.

The interaction between smoking and oral contraceptive (OC) use with respect to thrombogenesis was investigated by studying the effects of OC and smoking on urinary prostacyclin (PGI 2 ) and thromboxane A 2 (TxA 2 ) metabolite levels in smokers and nonsmokers. Sixty healthy women, aged 19–32 years, who were not taking any hormonal treatment for at least 3 months before initiating the study, were divided into three equal groups: OC users who smoked (N = 20), OC users who did not smoke (N = 20), and a control group of 10 smokers and 10 nonsmokers. Each OC treatment group was randomized to receive either norethindrone (NET) acetate (1 mg)/ethinyl estradiol (EE 2 ) (35 μg) (N = 10) or NET acetate (1 mg)/EE 2 (20 μg) (N = 10) daily for 3 months. Overnight urine collections and fasting blood samples were obtained at baseline and at the end of the 3-month study. Serum levels of NET and EE 2 , as well as urinary levels of cotinine and the stable metabolites of PGI 2 and TxA 2 , namely 6-keto-prostaglandin F 1α (6-keto-PGF 1α ) and thromboxane (TxB 2 ), respectively, were measured by specific immunoassays. Analysis of pre- to posttreatment changes in mean urinary 6-keto-PGF 1α and TxB 2 levels for each subgroup, as determined by smoking status and EE 2 dose, showed no statistically significant differences. Also, no significant differences were found in each subgroup with respect to changes in the 6-keto-PGF 1α /TxB 2 ratios. Large intersubject variability in urinary 6-keto-PGF 1α and TxB 2 levels were observed in all subgroups. The results of this study indicate that both low-estrogen–dose compounds, when used by smokers or nonsmokers, did not significantly alter the ratio of PGI 2 to TXA 2 metabolites, compared with pretreatment. However, the small number of subjects and the large intersubject variability in this study make it difficult to determine if there is a significant difference between the 20- and 30-μg EE 2 doses.

The purpose of the present report is to summarize the most important pharmacokinetic features of the new progestogens. In addition, the question of whether or not gestodene, in comparison to desogestrel, has an influence on the pharmacokinetics of ethinylestradiol (EE2) will be addressed.

Combined progestin–estrogen pills are an established and reliable contraceptive option used by women worldwide. Combined oral contraceptives (COCs) containing the progestins – gestodene, desogestrel or norgestimate – were developed to minimize androgenic side effects and are considered an effective, well-tolerated contraceptive option. Gestodene achieves contraceptive efficacy with the lowest dose of any progestin in a COC, and has an established and favorable short- and long-term tolerability profile. In this review we present an overview of the pharmacology, potency and tolerability of gestodene.