Combined oral contraceptives and mental health: Are adolescence and the gut-brain axis the missing links?

Combined oral contraceptives (containing synthetic forms of estradiol and progestins) are one of the most commonly used drugs among females. However, their effects on the gut-brain axis have not been investigated to a great extent despite clear evidence that suggest bi-directional interactions between the gut microbiome and endogenous sex hormones. Moreover, oral contraceptives are prescribed during adolescence, a critical period of development during which several brain structures and systems, such as hypothalamic-pituitary-gonadal axis, undergo maturation. Considering that oral contraceptives could impact the developing adolescent brain and that these effects may be mediated by the gut-brain axis, further research investigating the effects of oral contraceptives on the gut-brain axis is imperative. This article briefly reviews evidence from animal and human studies on the effects of combined oral contraceptives on the brain and the gut microbiota particularly during adolescence.

Analysis on the therapeutic effect of Cangfu Daotan Decoction combined with drospirenone and ethinylestradiol tablets (II) on patients with polycystic ovary syndrome.

OBJECTIVE: This study was designed to investigate the therapeutic effect of Cangfu Daotan Decoction (CDD) combined with drospirenone and ethinylestradiol tablets (II) on patients with polycystic ovary syndrome (PCOS). METHODS: Patients with PCOS were gathered from September 2020 to September 2022 and divided into the experimental group (n = 36), treated with CDD combined with drospirenone and ethinylestradiol tablets (II), and the control group (n = 41), received only drospirenone and ethinylestradiol tablets (II). Levels of sex hormone, obesity, blood glucose, blood lipid were detected and compared between the two groups pre- and post-treatment. The treatment efficacy, Traditional Chinese Medicine (TCM) syndrome score, adverse drug reactions, and pregnancy rate were compared as well. RESULTS: After treatment, the experimental group had a higher treatment efficacy (94.44% vs 73.17%, P < 0.05) and a higher pregnancy rate (44.44% vs 21.95%, P < 0.05) than the control group, but the difference in the incidence of adverse drug reactions was not statistically significant (P > 0.05). Compared with control group, TCM syndrome score and levels of fasting blood glucose, fasting insulin, homeostasis model assessment of insulin resistance (HOMA-IR), and waist circumference of the experimental group after treatment displayed remarkable reduction (P < 0.05), while the levels of estradiol (E2) and high-density lipoprotein cholesterol (HDL-C) showed a remarkable increase (P < 0.05). CONCLUSION: CDD in combination with drospirenone and ethinylestradiol tablets (II) may be effective in treating PCOS by improving obesity, glucose metabolism and lipid metabolism with no serious adverse events, making it a feasible clinical practice option.

The drospirenone only pill as a contraceptive option for breastfeeding women: First data on users' acceptability and newborn development.

BACKGROUND: Progestin-only pills (POPs) have been used for contraception in breastfeeding women for years. The existing guidelines allow the use of these contraceptives. METHODS: Multicenter study with a single visit and retrospective data review. The study involved 100 women who used a drospirenone-only pill (DRSP) for contraception for at least 5 months during breastfeeding. The study aimed to analyze for those successful users the impact on new-born development, the bleeding profile and evaluate user satisfaction. RESULTS: Analysis of the newborns showed that their growth parameters length and weight, were within the expected range of standard development. The mean birth weight was 3368 g, with the lowest recorded weight being 2860 g and the highest 5040 g. The median length of the newborns was 55 cm, ranging from 35 to 65 cm. All new-borns demonstrated appropriate growth within the established percentiles. Acceptability with the bleeding profile was rated with a VAS score: the mean acceptability rating was 82.8. Women aged 35 years or older reported significantly higher acceptability compared to younger women (≥35 years: mean = 88.4, SD = 16.5; <35 years: mean = 80.3, SD = 20.2) (p = 0.02). Sixty-one patients (N = 61; 61.0%; 95% CI: 50.7 - 70.4%) expressed willingness to continue using DRSP after breastfeeding. CONCLUSION: Among those patients who continued the use of the DRSP only-pill for 5 months, this study shows no negative impact for new-borns, with no clinical influence observed on their growth. Additionally, those users expressed high satisfaction with the bleeding profile of the pill.Clinical trial registration number: DRKS00028438 .

A phase I/II study evaluating the pharmacokinetics, pharmacodynamics, and safety of drospirenone as an oral contraceptive in Japanese women.

AIM: Drospirenone (DRSP) is a synthetic progestogen approved as a progestin-only pill for contraception in both the United States and Europe. Herein, we conducted a phase I/II study to evaluate the pharmacokinetics, pharmacodynamics, and safety of DRSP in Japanese women. METHODS: Single and multiple doses of 4 mg of DRSP were orally administered to healthy premenopausal Japanese women. In the multiple-dose period, 4 mg of DRSP was administered once daily for 24 days. Pharmacokinetics, hormone levels, and adverse events (AEs) were investigated. RESULTS: Twelve Japanese women participated in this study. The single- and multiple-dose pharmacokinetics of DRSP was similar to that reported in previous studies in Caucasians. In the multiple-dose period, no subject displayed a progesterone level of more than 5.03 ng/mL. AEs were observed in 11 (91.7%) subjects. The most common AE was genital hemorrhage, which was observed in six (50.0%) subjects, followed by diarrhea and acne in four (33.3%) subjects each. All AEs resolved or improved at the end of the study, and complete recovery was confirmed in all subjects at follow-up. CONCLUSIONS: The pharmacokinetics of DRSP in Japanese women was similar to that of previous studies performed in Caucasian women. Repeated administration of DRSP maintained low plasma progesterone levels indicating effective inhibition of ovulation. No notable safety concerns were observed. In this phase I/II study, DRSP had no obvious pharmacokinetic, pharmacodynamic, or safety issues to consider in Japanese women.

The efficacy of levonorgestrelintrauterine system, drospirenone & ethinylestradiol tablets (II) and dydrogesterone in preventing the recurrence of endometrial polyps.

OBJECTIVE: To analyze the efficacy of levonorgestrelintrauterine system, Drospirenone & ethinylestradiol tablets (II), and dydrogesterone in preventing the recurrence of endometrial polyps after hysteroscopic endometrial polypectomy. METHODS: One hundred seventy patients who underwent hysteroscopic endometrial polypectomy in the Gynecology Department of Tianmen First People's Hospital in Hubei Province from January 2022 to June 2023 were randomly divided into the levonorgestrelintrauterine system group, Drospirenone & ethinylestradiol tablets (II) group, dydrogesterone group, and a control group. The recurrence rates, endometrial thickness, and menstrual volume changes at 6 and 12 months post-operation were compared among these four groups. RESULTS: The recurrence rates in the levonorgestrelintrauterine system group, Drospirenone & ethinylestradiol tablets (II) group, and dydrogesterone group were lower than the control group, with statistical significance (P < 0.01), with the levonorgestrelintrauterine system group having the lowest recurrence rate. The endometrial thickness at 6 and 12 months post-operation in the levonorgestrelintrauterine system group, Drospirenone & ethinylestradiol tablets (II) group, and dydrogesterone group was thinner than that of the control group and thinner than pre-operation, with statistical significance (P < 0.01). The menstrual volume at 3 months post-operation in the levonorgestrelintrauterine system group, Drospirenone & ethinylestradiol tablets (II) group, and dydrogesterone group was significantly less than the control group, and less than the pre-operation volume. CONCLUSION: Dydrogesterone, drospirenone & ethinylestradiol tablets (II), and levonorgestrelintrauterine system all play a role in preventing the recurrence of endometrial polyps, but levonorgestrelintrauterine system is significantly better than dydrogesterone and Drospirenone & ethinylestradiol tablets (II) in terms of postoperative recurrence rate, endometrial thickness, menstrual changes, and compliance, and is worth promoting in clinical application.

Drospirenone 4 mg in a 24 + 4 regimen in women with contraindications to oestrogen use for contraception: bleeding patterns according to previous menstrual characteristics.

PURPOSE: A new POP consisting of 4 mg drospirenone (DRSP) for 24 days with a 4-day hormone-free interval was developed to improve bleeding predictability during POP use. The aim of this study was to evaluate the effect on bleeding patterns during use of this oral contraceptive (OC) in comparison with previous menstrual cycles before the start of OC use. METHODS: This is a pilot, prospective trial. A diary was used to collect information about daily bleeding and pelvic pain before and during treatment. During OC use, women were categorised as having (1) unscheduled bleeding or spotting days (UB), (2) scheduled bleeding or spotting days (SB) and (3) absence of bleeding/spotting (AB). SF-36 and FSFI questionnaires were used to quantify health-related quality of life and the quality of sexual life in sexually active participants. RESULTS: Eighteen out of twenty-five (72%) women completed the entire follow-up. Women with UB (44.4%) were older at inclusion (p < 0.001) and had higher BMIs (p = 0.02) than those with AB (22.2%) or SB (33.4%). Women recorded a significant reduction of menstrual flow intensity during OC use (p < 0.0001). Those with UB also experienced a significant reduction of menstrual pain intensity (p = 0.006). Women with SB during OC use had a longer baseline cycle than those who reported UB during OC use (p = 0.008). Satisfaction with this OC was very high (8.4 ± 2.2 points) with no modification in SF-36 and FSFI values. CONCLUSION: A DRSP-only pill is a good OC option for women with contraindications to oestrogen use. Features of the menstrual cycle before the start of OC use may be used to predict associated changes in bleeding patterns.

Ultrasound-Assisted Extraction, Followed by Gas Chromatography-Mass Spectrometry for the Simultaneous Quantification of Ethinyl Estradiol and Drospirenone in Contraceptive Formulations.

Contraceptive tablets typically contain a combination of two synthetic versions of an estrogen and a progestogen, which work together to inhibit the ovulation process. An accurate and precise quantification of these components is essential for contraceptive producers. In this study, we have developed the first gas chromatography-mass spectrometry (GC-MS) method for the simultaneous quantification of 17α-ethinyl estradiol (EE) and drospirenone (DP) in contraceptive formulations. Under the final working conditions, analytes were extracted from the solid by ultrasound-assisted extraction (15 min) in methanol. The resulting suspension was diluted in ethyl acetate, subjected to centrifugation and, finally, the supernatant was directly injected into the GC-MS system. No derivatization reagents were utilized. To correct for instrumental variations, calibration was performed using the internal standard method, with cholesterol as the internal standard. A good linearity was achieved throughout the calibration range for both EE (3-12 µg mL-1) and DP (300-1200 µg mL-1), with R2 values exceeding 0.99. Trueness, assessed in terms of percentages of recovery, was also found to be satisfactory for both analytes, with recovery rates of 106 ± 8% for EE and 93 ± 9% for DP. Furthermore, intra-day and inter-day precision studies yielded relative standard deviation values below 6% for both analytes. In terms of sensitivity, the instrumental limits of detection were 0.25 µg mL-1 for EE and 6.6 µg mL-1 for DP, and the instrumental limits of quantification 0.82 µg mL-1 for EE and 22 µg mL-1 for DP. The method was successfully applied to the analysis of contraceptive tablets from three different pharmaceutical companies. No differences were observed between the measured and the declared amount of active principle per tablet, demonstrating the applicability of the procedure. In addition, a stability study conducted on both the standards and sample extracts demonstrated that they can be stored at room temperature for a minimum period of seven days.

The drospirenone (DRSP)-only pill: clinical implications in the daily use.

OBJECTIVES: Progestins used in contraception are either components of combined hormonal contraceptives or are used as a single active ingredient. Progestins are highly effective in long-term contraception and have a very good safety profile with very few contraindications. METHODS: An oestrogen-free ovulation inhibitor POP has been authorised in the USA and the EU. It contains 4 mg of drospirenone (DRSP). The hormone administration regimen of 24 days followed by a 4-day hormone-free period was chosen to improve bleeding control and to maintain oestradiol concentrations at early follicular- phase levels, preventing oestrogen deficiency. RESULTS: Clinical trials have demonstrated high contraceptive effectiveness, a very low risk of cardiovascular risk events and a favourable bleeding pattern. Due to the long half-life of DRSP (30-34 h), the effectiveness is maintained even in case of a forgotten pill on a single occasion. Studies involving deliberate 4 days in one cycle 24-hour delays in taking a pill have demonstrated that ovulation inhibition is maintained if a single pill is missed. CONCLUSIONS: This review article will describe the clinical impact in the daily use of the 4 mg DRSP only pill and the resulting data on the effectiveness and safety of this hormonal contraceptive.

The 4 mg drospirenone-only pill improves the bleeding profile in comparison to 0.075 mg desogestrel and achieves high contraceptive efficacy even with a 24 h missed pill window.

A new progestin-only pill (POP): the impact of drospirenone-only pill 4 mg 24 + 4 on coagulation markers and bleeding patterns.

PURPOSE: Progestin-only pills (POPs), compared to combined, are not associated with an increased risk of venous thromboembolism, but are associated with a poor cycle control. The aim of this study was to evaluate the impact of a new POP [4 mg drospirenone (DRSP) for 24 days with a 4-day hormone-free interval] on some coagulation markers (both procoagulant and fibrinolytic) and to describe its impact on bleeding patterns. MATERIALS AND METHODS: This is a prospective trial, based on serum evaluation of following coagulation markers and tests: Factor (F) X, F VIII, F V, INR, aPTT, Protein S and antithrombin III. A 'bleeding diary' was used to categorise women as having (1) unscheduled bleeding, (2) scheduled bleeding and (3) amenorrhoea. Thirty patients were followed for six 28-day intake cycles, with a follow-up at the end of the 3rd and 6th cycles. RESULTS: There was a significant decrease of F X (p = 0.03) (-5.7% at cycle 6). No significant changes have been observed for F VII, F V and INR. A significant increase in aPTT (p = 0.01 at 3 cycles), Protein S (p = 0.0006 at 3 cycles) and antithrombin III (p < 0.0001 at 3 cycles) was recorded. This non-deteriorating coagulation impact was associated with a significant and progressive reduction of days of scheduled and unscheduled bleeding in users between cycles 4 and 6 (from 1.3 ± 0.2 days at cycle 4 to 0.8 ± 0.1 days at cycle 6 and from 2.6 ± 0.4 days at cycle 4 to 0.6 ± 0.2 days at cycle 6, respectively, p < 0.0001). CONCLUSIONS: DRSP 24 + 4 use was associated with a non-deteriorating effect on coagulation markers and a significant progressive reduction of days of scheduled and unscheduled bleeding.

Contraception with DRSP 24 + 4 was associated with a non-deteriorating effect on coagulation markers and a significant progressive reduction of days of scheduled and unscheduled bleeding.

Abiotic transformation of synthetic progestins in representative soil mineral suspensions.

Altrenogest (ALT), drospirenone (DRO), and melengestrol acetate (MLA) are three highly potent synthetic progestins that can be released into agricultural soils, while their fate in soil minerals remains unclear. This study explored the transformation of these progestins in MnO2, SiO2, and ferrihydrite suspensions and identified their transformation products (TPs) via high resolution mass spectrometry and density functional theory calculations. Transformations were only observed for DRO and MLA in SiO2 suspension and ALT in MnO2 suspension (half-lives = 0.86 min - 9.90 day). ALT transformation was facilitated at higher MnO2 loadings, while DRO and MLA transformations were inhibited at higher SiO2 loadings. These data indicated that hydrophobic partitioning interaction was dominant at higher SiO2 loadings rather than specific interaction, which limited subsequent surface-catalyzed transformation. ALT transformation rate decreased with increasing pH because MnO2 reduction requires proton participation. In contrast, relatively high pH facilitated MLA and DRO transformation, indicating that base-catalyzed hydrolysis occurred in SiO2 suspension. The clustermap demonstrated the formation of abundant TPs. Lactone ring and acetoxy group hydrolysis was the major transformation pathway for DRO and MLA, with estimated yields of 57.7% and 173.2% at 6 day, respectively. ALT experienced C12 hydroxylation and formed the major TP 326g (yield of 15.4% at 8 hr). ALT also experienced allyl group oxidation and subsequent C5 hydroxylation, forming the major TP 344a (yield of 14.1% at 8 hr). This study demonstrates that TPs of metastable progestins are likely the main species in soils and that TP identification is a particular priority for risk assessment.

Estetrol-Drospirenone combination oral contraceptive: a clinical study of contraceptive efficacy, bleeding pattern and safety in Europe and Russia.

OBJECTIVES: To assess the contraceptive efficacy, bleeding pattern and safety of a combined oral contraceptive containing estetrol (E4) 15 mg and drospirenone (DRSP) 3 mg. DESIGN: Multicenter, open-label, phase 3 trial. SETTING: Sixty-nine sites in Europe and Russia. POPULATION: Sexually active women aged 18-50 years with regular menstrual cycles and body mass index ≤35 kg/m2 . METHODS: E4/DRSP was administered in a 24 active/4 placebo regimen for up to 13 cycles. Visits were scheduled during Cycles 2, 4, 7 and 10 and after completing treatment during which adverse events (AEs) were collected. Participants recorded medication intake, vaginal bleeding/spotting, use of other contraceptive methods and sexual intercourse on a daily diary. MAIN OUTCOME MEASURES: Pearl Index (PI) for women 18-35 years (overall and method-failure), bleeding pattern and AEs. RESULTS: A total of 1553 women aged 18-50 years, including 1353 from 18 to 35 years old, received the study medication. PI was 0.47 pregnancies/100 woman-years (95% CI 0.15-1.11); method failure PI was 0.29 pregnancies/100 woman-years (95% CI 0.06-0.83). Scheduled bleeding/spotting occurred in 91.9-94.4% of women over Cycles 1 to 12 and lasted a median of 4-5 days per cycle. The percentage of women with unscheduled bleeding/spotting episodes decreased from 23.5% in Cycle 1 to <16% from Cycle 6 onwards. The most common AEs were headache (7.7%), metrorrhagia (5.5%), vaginal haemorrhage (4.8%) and acne (4.2%). One treatment-related serious AE was reported, a lower extremity venous thromboembolism. One-hundred and forty-one (9.1%) women discontinued study participation because of treatment-related adverse events. CONCLUSION: E4/DRSP provides effective contraception, a predictable bleeding pattern and a favourable safety profile. TWEETABLE ABSTRACT: A phase 3 trial with E4/DRSP shows high contraceptive efficacy, a predictable bleeding pattern and favourable safety profile.

Evaluation of the food effect on a drospirenone only contraceptive containing 4 mg administered with and without high-fat breakfast in a randomised trial.

BACKGROUND: The objective of the present trial was to assess the difference in pharmacokinetics (PK) of an oral test preparation containing 4 mg drospirenone (DRSP) under fasting conditions compared to PK upon food intake after single dose administration. METHODS: Open label, single centre, two-treatment, two-sequence, crossover study in 24 healthy female volunteers, with duration of 1 day per sequence and with a real wash-out period of 14 days to investigate the relative bioavailability of DRSP with both forms of administration. The 90% confidence intervals (CI) were calculated for the intra-individual ratio (test with food vs. without food) of the PK endpoints Area under the curve; 0-72 h [AUC(0-72 h)] and maximal plasma concentration [Cmax] of DRSP. RESULTS: The 90% CI calculated by analysis of variance using logistic transformation (ANOVA-log) for the endpoint, intra-individual ratio (Test 'A' = with food intake) vs. Test 'B' = without food intake) of AUC(0-72 h) of drospirenone was between 104.72 and 111.36%. The 90% CI calculated by means of ANOVA- log for the endpoint intra-individual ratio (Test 'A' vs. Test 'B') of Cmax of DRSP was between 118.58 and 141.10%. The mean relative bioavailability of the test with food 'A' compared to the Test without food 'B' after single dose administration based on the endpoints AUC(0-72 h) was 107.99%; for the endpoint Cmax it was 129.35%. CONCLUSIONS: The rate of absorption, based on the endpoint Cmax of DRSP was increased by about 30% under fed conditions. With respect to consumer habits, this may represent a relevant benefit for contraceptive safety, as the time span between food consumption and pill intake does not play a role. IMPLICATIONS: Our results suggest that the food intake has no impact on the absorption of 4 mg DRSP in the management of contraception. This increases the contraceptive efficacy as no interference with food is expected when consuming the oral formulation under real life conditions. TRAIL REGISTRATION: Trial registration number: EudraCT-No: 2012-004,309-28.

Bleeding profile of women with cardiovascular risk factors using a drospirenone only pill with 4 mg over nine cycles compared to desogestrel 0.075 mg.

OBJECTIVE: Progestin-only pills are associated with irregular bleeding patterns, including amenorrhea. Desogestrel (DSG) 75 mcg, a pill that inhibits ovulation, shows poor cycle control that may harm acceptability and compliance. A Drospirenone (DRSP)-only pill was developed with 24 & 4 days of active & placebo days every 28-day cycle to improve cycle control. STUDY DESIGN: A phase III study in healthy women aged 18 to 45 years was performed to compare the bleeding profile of women taking a DRSP versus DSG over nine cycles. 249 women were older > 35 years: 173 using DRSP and 73 DSG. 259 women had a BMI > 25 kg/m2: 189 using DRSP and 70 DSG and 340 women were smokers: 237 using DRSP and 103 DSG. The amount of unscheduled bleeding/spotting days was analyzed in each of these sub-groups and compared statistically. RESULTS: Age: During cycles 2-4, the mean number of unscheduled bleeding days and spotting was 8.1 (SD10.53) for DRSP and 20.1 (19.41) for DSG; p = .0089. BMI > 25 kg/m2: During cycles 2-4 the mean number of unscheduled bleeding days and spotting was 7.8 (SD 12.18) for DRSP and 17.7 for DSG (SD 19.39); p = .0001. Smokers: During cycles 2-4, the mean number of unscheduled bleeding days and spotting was 9.6 (SD 11.69) for DRSP and 17.4 for DSG (SD 17.47); p = .0016. CONCLUSIONS: These analyses show the improvement in the bleeding profile of women with specific cardiovascular risk factors using the DRSP only oral contraceptive product compared to DSG.ImplicationsAn improvement in the bleeding profile of women with specific cardiovascular risk factors like age > 35 years, BMI > 25kg/m2, and smokers using the DRSP only oral contraceptive product is described.Herby a higher contraceptive efficacy in these patients that additionally benefit from estrogen-free contraceptive methods is expected.

The progestin-only pills drospirenone 4 mg and desogestrel 0.075 mg as an option for the management of dysmenorrhea and mastodynia.

INTRODUCTION: Dysmenorrhea and mastodynia are the most common gynecologic pain causes in women of all ages and races during their reproductive life. The following study aimed to show the influence of two POP´s in the development of dysmenorrhea and mastodynia after nine months of use. MATERIAL AND METHODS: A total of 858 women with 6691 drospirenone (DRSP) cycles and 332 women with 2487 desogestrel (DSG) cycles were analyzed. Women included in this study were all child-bearing potentials, at risk of pregnancy, agreeing to use only the study medication for contraception for the duration of the study medication treatment, aged 18 to 45. RESULTS: At screening, 168 (19.6%) of the 858 patients using DRSP and 64 (19,3%) of the DSG patients reported that they had suffered from dysmenorrhea within six cycles prior to the first visit before starting with the medication. 20,2% of the DRSP and 10,9% of the DSG group had a sever dysmenorrhea. After 9 cycles this was reduced to 0,6% and 3,1% respectively. In total, 96 women (11.2%) in the DRSP and 49 (14,8%) experienced mastodynia within six cycles before the screening. Of these 91.6% in the DRSP group and 91,8% in the DSG group had no or mild mastodynoa at follow-up. DISCUSSION: The progestins 4 mg and desogestrel 0,075 mg showed a marked effect in the non-contraceptive aspects of dysmenorrhea and mastodynia so that new possibilities are opened for these two benign gynecological diseases. Future studies must reaffirm these first data.

Effect on the cardiovascular independent risk factor lipoprotein(a) in overweight or obese PCOS patients with ethinyl-estradiol/drospirenone alone or plus orlistat.

OBJECTIVE: This study aimed to assess the effect on the cardiovascular independent risk factor Lipoprotein(a) [Lp(a)] in overweight or obese polycystic ovary syndrome (PCOS) patients with ethinyl-estradiol/drospirenone (EE/DRSP) alone or plus orlistat. METHODS: In this randomized controlled prospective study, 66 PCOS patients with overweight or obesity were matched according to age and BMI. All participants were randomly divided into two groups to receive EE/DRSP plus Orlistat (n = 33) or EE/DRSP alone (n = 33) for 3 months. Changes in cardiovascular risk factors including Lp(a), CRP, LDL-C, anthropometric assessments, variations in sex hormones related parameters, and in glucolipid metabolic index were evaluated after the intervention. RESULTS: Lp(a) and CRP were significantly decreased at 3 months only in the EE/DRSP plus Orlistat group. There were significant reductions in LDL-C, weight, BMI, waist circumference (WC), body fat percentage (BFP), FT in both groups compared to baseline. However, these reductions were significantly greater in EE/DRSP plus Orlistat group. The levels of HDL-C, TG, and SHBG significantly increased, while TT and LH significantly decreased in both groups over time. TC, FINS, FPG were not significantly changed in both groups after the intervention. CONCLUSIONS: This is the first study found that EE/DRSP plus Orlistat could significantly decrease Lp(a) in overweight or obese PCOS patients. This result can be assessed as particularly important, because Lp(a) is well-known as an independent risk factor predicting an increased risk of cardiovascular diseases (CVDs).

Effect of orlistat during individualized comprehensive life-style intervention on visceral fat in overweight or obese PCOS patients.

ObjectiveTo investigate the effect of orlistat combined with drospirenone/ethinylestradiol tablets (DRSP/EE) on the visceral fat area (VFA) compared to DRSP/EE-alone in overweight or obese patients with polycystic ovary syndrome (PCOS).Methods90 PCOS patients [body mass index (BMI) ≥24kg/m2] were recruited for a prospective, open-label, 1:2 paired 3-monthly study. All were included during the per-protocol defined recruitment time and numbered according to the entry-order: group-1: No.1-60, orlistat plus DRSP/EE; group-2: No.61-90, DRSP/EE-alone. Both groups received the same comprehensive intervention in terms of individualized, standardized management and lifestyle monitoring such as diet and exercise. Primary study-endpoint was VFA, secondary endpoints were anthropometric indices, sex hormones and glucolipid metabolism. Within- and between-group analyses were performed.ResultsVFA [cm2] in group-1 after treatment decreased significantly (p = 0.001), and the between-group comparison was highly significant (p = 0.001). Body weight, hip circumference (HC), BMI, body fat (BF), free testosterone (FT) and low-density lipoprotein-cholesterol (LDL-C) significantly decreased in both groups (within-group analysis); the decrease in group-1 was significantly greater than in group-2 (p < 0.05). Systolic and diastolic blood pressure (SBP/DBP) and fasting plasma glucose (FPG) in group-1 were significantly decreased, significantly more in group-1 than in group-2 (p < 0.05).ConclusionThis study is the first to investigate the effect of orlistat combined with DRSP/EE in overweight or obese PCOS patients compared with using DRSP/EE-alone. Orlistat combined with DRSP/EE was better than using DRSP/EE-alone in reducing VFA, body weight, FT, BP and FPG, which provides evidence for the choice of rational drug use in clinical practice.

A novel estetrol-containing combined oral contraceptive: European expert panel review.

PURPOSE: Despite considerable advances in recently developed combined oral contraceptives (COCs), resulting in lower rates of adverse events while maintaining contraceptive efficacy, there is interest in further innovation. MATERIALS AND METHODS: Estetrol (E4), a native oestrogen, and progestin drospirenone (DRSP) were combined in a new COC. A European expert panel reviewed the pharmacology, efficacy, and safety and tolerability of this combination. Their findings are presented as a narrative review. RESULTS: E4 15 mg/DRSP 3 mg in a 24/4 regimen provided effective contraception with good cycle control, characterised by a predictable regular bleeding pattern and minimal unscheduled bleeding, together with a good safety profile. The combination was associated with high user satisfaction, well-being, and minimal changes in body weight. The effects on endocrine and metabolic parameters were limited, and the combination was found to have a limited impact on liver function and lipid and carbohydrate metabolism. Moreover, its effect on several haemostatic parameters was lower than that of comparators containing ethinyl oestradiol (EE) 20 µg/DRSP 3 mg and EE 30 µg/levonorgestrel 150 µg. CONCLUSION: E4 15 mg/DRSP 3 mg provides safe and effective contraception, with high user satisfaction and predictable bleeding. Further research will evaluate the long-term safety of the COC.

A novel estetrol-containing combined oral contraceptive: European expert panel review.

PURPOSE: Despite considerable advances in recently developed combined oral contraceptives (COCs), resulting in lower rates of adverse events while maintaining contraceptive efficacy, there is interest in further innovation. MATERIALS AND METHODS: Estetrol (E4), a native oestrogen, and progestin drospirenone (DRSP) were combined in a new COC. A European expert panel reviewed the pharmacology, efficacy, and safety and tolerability of this combination. Their findings are presented as a narrative review. RESULTS: E4 15mg/DRSP 3 mg in a 24/4 regimen provided effective contraception with good cycle control, characterised by a predictable regular bleeding pattern and minimal unscheduled bleeding, together with a good safety profile. The combination was associated with high user satisfaction, wellbeing, and minimal changes in body weight. The effects on endocrine and metabolic parameters were limited, and the combination was found to have a limited impact on liver function and lipid and carbohydrate metabolism. Moreover, its effect on several haemostatic parameters was lower than that of comparators containing ethinyl oestradiol (EE) 20mg/DRSP 3 mg and EE 30mg/levonorgestrel 150mg. CONCLUSION: E4 15 mg/DRSP 3 mg provides safe and effective contraception, with high user satisfaction and predictable bleeding. Further research will evaluate the long-term safety of the COC.

The effect of combined oral contraceptives containing drospirenone and ethinylestradiol on serum levels of amino acids and acylcarnitines.

INTRODUCTION: Metabolome variations have long been associated with normal hormonal fluctuations, and similar effects, related to the use of early generation synthetic hormones as a means of contraception, have also been identified. OBJECTIVE: We investigated the serum amino acid and acylcarnitine profiles induced by the use of combined oral contraceptives (COCs) consisting of Ethinylestradiol (EE) and a 4th generation progestin, Drospirenone (DRSP). METHOD: Gas chromatography mass spectrometry and liquid chromatography with tandem mass spectrometry was used to identify and quantify the serum amino acids and acyl carnitine levels in 24 controls, 25 DRSP/20EE users and 26 DRSP/30EE users. RESULTS: Of the 26 amino acid compounds measured, 13 showed significant variations in abundance between the control and COC user groups. Although none of the 21 acylcarnitine compounds detected were statistically significant with regards to group variations, a trend, related the EE concentration, was observed. The detected metabolome disparities corresponded to that identified for earlier generation COCs, all pointing toward increased oxidative stress levels in the user groups. CONCLUSION: These findings suggest that the clinical complications associated with these COCs could, to some extent, be alleviated by the simultaneous use of antioxidants. The study also highlights the role that targeted metabolomics could play in the elucidation of the underlying mechanisms of drug-induced severe effects.

Risk of sexual dysfunction with progestin-based contraceptives in women of child-bearing age.

PURPOSE: To examine whether there is a positive association between sexual dysfunction (SD) and different types of progestin-based contraceptives. METHODS: Nested case-control study in women of child-bearing age (15-45 years) from the IQVIA® Ambulatory electronic medical record database from 2008 to 2018. Cases defined by diagnosis of sexual dysfunction identified by international classification for disease clinical modification code 9th and 10th. Each case was matched to four controls and rates of prescriptions of the following were compared: levonorgestrel intra-uterine device (IUD), progestin, and ethinyl estradiol (EE) combined oral contraceptive (COC) formulations including levonorgestrel, norgestimate, drospirenone, desogestrel, norethindrone, and norgestrel; etonogestrel vaginal ring; and medroxyprogesterone injection. RESULTS: Overall, 6689 cases of patients with SD were matched to 26,756 matched controls. Compared with matched controls, more subjects with SD used levonorgestrel IUD (OR 1.24, 95% CI 1.08-1.44), EE-levonorgestrel COC (OR 1.18, 95% CI 1.00-1.41), EE-drospirenone (OR 1.28, 95% CI 1.00-1.67), and medroxyprogesterone (OR 1.38, 95% CI 1.12-1.70). The use of norgestrel exhibited a protective effect (OR 0.83, 95% CI 0.73-0.95). When using the EE-levonorgestrel COC as a comparator, norgestrel users exhibited a protective effect (OR 0.70, 95% CI 0.57-0.87) while no other contraceptives showed a statistically significant difference in association with SD. CONCLUSION: Our study found an increase in the use of levonorgestrel (COC and IUD), drospirenone, and medroxyprogesterone in subjects with SD. The risk of contraceptives did not differ when compared with oral levonorgestrel. The small association size and lack of difference between drug formulations suggest a minimal impact of progestin-based contraceptives on sexual dysfunction.