Combination Of Ethinylestradiol Research Articles

Emergency Contraception

There have been numerous attempts to control fertility after unprotected sexual intercourse (UPSI). From very bizarre methods like the vaginal application of Coca Cola to the more serious attempts using calcium antagonists influencing fertility parameters in sperm to hormonal methods or intrauterine devices. So far, hormonal methods preventing or delaying ovulation have proved to be the most popular starting with the combination of ethinyl estradiol and levonorgestrel (LNG), known as the Yuzpe regimen. The first dose had to be taken within 72 hours of UPSI, a second one 12 hours later. Later on, LNG alone, at first in a regimen similar to the Yuzpe method (2 × 0.75 mg 12 hours apart) showed to be more successful, eventually resulting in the development of a 1.5 mg LNG pill that combined good efficacy with a high ease of use. Several efficacious and easy to use methods for emergency contraception (EC) are available on the market today with the most widely spread being LNG in a single dose of 1.5 mg (given as one tablet of 1.5 mg or 2 tablets of 0.75 mg each) for administration up to 3 days (according to WHO up to 5 days) after UPSI. Its limitations are the non-optimal efficacy which is decreasing the later the drug is taken and the fact that it is only approved for up to 72 hours after UPSI. This regimen has no effect on the endometrium, corpus luteum function and implantation, is not abortive and don't harm the fetus if accidentally taken in early pregnancy. It has no impact on the rate of ectopic pregnancies. It has become the standard method used up to this day in most countries. Since the mid 1970s copper IUDs have been used for EC, which show a high efficacy. Their disadvantages lie in the fact that EC is considered an off label use for most IUDs (not for the GynFix copper IUD in the European Union) and that they might not be acceptable for every patient. Furthermore IUD-insertion is an invasive procedure and it is required trained providers and sterilized facilities. Mifepristone in the dosages of 10 or 25 mg is used with good results as an emergency contraceptive in China for up to 120 hours after UPSI, but has never received any significant consideration in Western countries. While high doses of mifepristone has an effect on endometrial receptivity and will inhibit ovulation if given in the follicular phase and prevent implantation if given in the early luteal phase, low doses such as 10 mg has no impact on the endometrium. Mifepristone does not increase the rate of ectopic pregnancies. The most recent development is the approval of the selective progesterone receptor modulator ulipristal acetate (UPA) in the dosage of 30 mg for EC up to 5 days after UPSI, combining the safe and easy application of the single dose LNG pill with an even higher efficacy. It has shown to be more efficacious than LNG and can be used for up to 120 hours after UPSI; the difference in efficacy is highest for 0–24 hours, followed by 0–72 hours following UPSI. No VTE has been reported following UPA-administration or any progesterone receptor modulator. No effect on endometrium, corpus luteum function and implantation has been observed with doses used for EC. Independent of the substance it should be noted that, if there is a choice, the intake of an oral emergency contraceptive pill should happen as soon as possible after the risk situation. A preexsisting pregnancy must be excluded. Possible contraindications and drug interactions must be considered according to the individual special product informations.

Combination of injectable ethinyl estradiol and drospirenone drug-delivery systems and characterization of their in vitro release

Our aim was to investigate the in vitro release and combination of ethinyl estradiol (EE) and drospirenone (DRSP) drug-delivery systems. DRSP poly(lactic-co-glycolic acid) (PLGA) microparticles and organogels containing DRSP microcrystals were prepared and characterized with regard to properties influencing drug release. The morphology and release kinetics of DRSP PLGA microparticles indicated that DRSP is dispersed in the polymer. The in vitro release profiles correlated well with in vivo data. Although DRSP degradation is known to be acid-catalyzed, DRSP was relatively stable in the PLGA matrix. Aqueous DRSP PLGA microparticle suspensions were combinable with EE PLGA microparticles and EE poly(butylcyanoacrylate) (PBCA) microcapsules without interacting. EE release from PLGA microparticles was faster than DRSP release; EE release is assumed to be primarily controlled by drug diffusion. Liquid-filled EE PBCA microcapsules were shown to be more robust than air-filled EE PBCA microcapsules; the bursting of microcapsules accelerating the drug delivery was therefore delayed. The drug release profile for DRSP organogels was fairly linear with the square root of time. The system was not combinable with EE PBCA microcapsules. In contrast, incorporation of EE PLGA microparticles in organogels resulted in prolonged EE release. The drug release of EE and DRSP was thus approximated.

Renal infarction due to oral contraceptive pills.

A previously healthy, 35-year-old woman, mother of two children, presented with a 3-day history of abdominal discomfort, vomiting and anuria for 2 days. She had no history of diabetes or hypertension. She had been using a combination of ethinylestradiol and drospirenone as a contraceptive for the previous 3 years. Her investigations at presentation were: serum creatinine: 7.9 mg/dL (698 μmol/L), blood urea nitrogen: 185 mg/dL (66 mmol/L), serum proteins: 8.2 g/dL, serum albumin: 4.5 g/dL, serum homocysteine: 4.2 μmol/L (0.56 mg/L), haemoglobin: 11.2 g/dL, total leucocyte count: 4800/mm3, platelet count: 340 × 109/L, prothrombin time: 15.0 sec (control: 13.0 sec), activated partial thromboplastin time: 28.0 sec (control: 30.0 sec), thrombin time: 10.0 sec (control: 8.0 sec), bleeding time: 4.0 min (reference range: 2.0–7.0 min), clotting time: 5.0 min (reference range: 5.0–7.0 min), serum fibrinogen: 444 mg/dL (range: 150–400 mg/dL) and D-dimer: 1.7 μg/mL (range: 0.5 μg/mL). Kidney sizes on ultrasound were right: 12.4 × 4.6 cm and left: 11.5 × 4.4 cm. Doppler of the renal arteries revealed severe decrease and pruning of the segmental, inter-lobar and arcuate vessels and absence of the cortical blush in both of the kidneys. Urine dipstick examination for proteins was negative. A renal biopsy was done after a session of haemodialysis. It revealed coagulative necrosis (infarct) of the cortex of the kidney, and the artery included in the biopsy was obstructed by fibrin thrombus (Figure 1). She was not pregnant and had no congenital heart disease. There was no history of acute gastroenteritis, trauma or snakebite. There was no history or clinical features suggestive of haemolytic uraemic syndrome. There were no schistocytes on peripheral smear. Electrocardiogram showed normal sinus rhythm with no ischaemic or chamber enlargement changes. Echocardiography revealed normal cardiac chambers and normal valves. The reports of anti-thrombin III: 0.25 g/L (range: 0.19–0.31 g/L), protein C: 90% (range: 70–160%) and protein S: 80% (range: 60–150%). Prothrombin time and partial thromboplastin times were not prolonged in order to investigate for factor V Leiden mutation. Flow cytometry did not find a reduction in CD 55 and CD 59 on red blood cells, thus excluding paroxysmal nocturnal haemoglobinuria. Anti-phospholipid antibodies, lupus antibody, anti-nuclear antibodies and anti-double-stranded DNA were negative. Fig. 1. Renal biopsy showing cortical necrosis and the artery occluded by fresh fibrin thrombus (arrow) in an artery (SMPASX40). The patient did not regain renal function. She was initiated on continuous ambulatory peritoneal dialysis. One of the adverse effects of oral contraceptive pills is arterial thrombosis. There are experimental reports of acute cortical necrosis in rats induced by oestrone and vasopressin administration [1]. There are a few reports of acute cortical necrosis in patients who used oral contraceptives, but these patients had other features like factor V Leiden mutation [2] and smoking [3].

Reciprocal coordination of a combination oral contraceptive containing desogestrel+ethinyl estradiol on the expression of LOX-1 and LDLR in placental trophoblast cells

Background The aim of this study was to assess the consistency of antiatherosclerotic potential of a combination oral contraceptive steroid (ethinyl estradiol+desogestrel) by rating its effect on the differential expression of the low-density lipoprotein receptor (LDLR) and lectin-like oxidized LDL (LOX-1) receptor. Study Design Cells from placental trophoblast cell line (JAR) and differentiated primary placental trophoblast cells isolated from term human placentae were used for this study. Expressions of LOX-1 and LDLR were assessed by immunoblot and immunocytochemistry assays. Differential effects of the constituent steroids in the combination of ethinyl estradiol and desogestrel were verified on the expression profile of the receptors. Results Desogestrel opposed the effect of ethinyl estradiol on LOX-1 expression, and when used in combination, the combination oral contraceptive reduced the expression of LOX-1 in contrast to LDLR. The characteristic change in the expressions of LOX-1 and LDLR showed an antiatherosclerotic improvisation at the unique combination of ethinyl estradiol (10 ng/mL) and desogestrel (20 ng/mL). Conclusion The aforesaid combination of ethinyl estradiol and desogestrel keeps LOX-1 and LDLR reciprocally expressed in antiatherosclerotic mode.

Development and evaluation of matrix type transdermal patch of ethinylestradiol and medroxyprogesterone acetate for anti-implantation activity in female Wistar rats

Background Medroxyprogesterone acetate (MPA), which increases high-density lipoprotein level, has not been used as a progestin in combination with estrogen in a transdermal patch to date. The aim of the research was to develop and evaluate a matrix-type transdermal drug delivery (TDD) system of a combination of ethinylestradiol (EE) and MPA for interception. Study Design The transdermal patch of EE and MPA was prepared using various film-forming polymers with and without n-dibutyl phthalate as plasticizer and with glycerol and sodium lauryl sulphate as penetration enhancer. All formulations were assayed using UV spectrophotometer by Vierordt's equation for EE and MPA. Results The percentage cumulative release of F6 (optimized formulation) named as ‘AGARPRU’ was found to be 99.94%±1.25% and 69.99%±1.02% (mean±SD) through rat skin and 92.69%±2.22% and 53.51%±2.11% (mean±SD) through cadaver skin for EE and MPA, respectively. Pharmacodynamic studies of ‘AGARPRU’ in female Wistar rats showed 100% anti-implantation activity. The in vivo results showed prolonged T max of 36 h for both EE and MPA after transdermal administration compared to oral route (2 h). Moreover, the area under the curve of EE and MPA revealed an increase in bioavailability after transdermal administration as compared to oral route. Conclusion These findings suggested that TDD formulation aimed for postcoital antifertility activity has been successfully developed in female Wistar rats.

Effect of a combination oral contraceptive (desogestrel+ethinyl estradiol) on the expression of low-density lipoprotein receptor and its transcription factor (SREBP2) in placental trophoblast cells

Background This in vitro study deals with the effect of a combination oral contraceptive steroid — desogestrel and ethinyl estradiol — on the expression of low-density lipoprotein receptor (LDLR) and its transcription factor (SREBP2) in assessing the functional effectiveness of the LDLR. Study design Differentiated primary placental trophoblast cells isolated from term human placentae and cells from Jar cell line were used for the study. Low-density lipoprotein receptor and SREBP2 expressions were assessed by immunocytochemistry and immunoblot assays with and without combination contraceptive steroid challenge. Functional activity of LDLR was studied by rating the profile of cellular uptake of fluorescent Dil-LDL (1,1′-dioctadecyl-3,3,3′,3′-tetramethylindocarbocyanin perchlorate-LDL). Quantitation of Dil-LDL was done spectrofluorometrically. Results Variation of concentration(s) of either of the components of a combination preparation (desogestrel and ethinyl estradiol) showed a comparable change in the expressions of LDLR and SREBP2 to attain their optimal levels. Maximum expression and a significant functional effectiveness were observed at a unique combination of desogestrel (20 ng/mL) and ethinyl estradiol (10 ng/mL). Conclusion The stimulatory effect of a combination contraceptive steroid on LDLR expression is an associated phenomenon of the contraceptive-mediated stimulation of SREBP2 expression.

Drospirenone/Ethinylestradiol: A Review on Efficacy and Noncontraceptive Benefits

Considerable advances have been made in the field of combined oral contraceptives since their introduction 50 years ago. This ongoing evolution has been focused on reducing the estrogen dose and synthesizing new progestogens. A recently launched combination of ethinylestradiol 20 µg and drospirenone 3 mg demonstrates the advantages of a lower estrogen dose with the antimineralocorticoid activity of drospirenone that is responsible for the drug's significant antiandrogenic and antimineralocorticoid effects, reflected clinically in lower rates of adverse events including less fluid retention. In addition to the drug's contraceptive efficacy, its effects on the skin and other classic noncontraceptive benefits, the ethinylestradiol 20 µg and drospirenone 3 mg combination has demonstrated highly satisfactory results in women with premenstrual dysphoric syndrome.

Effects of vitamin E and folic acid on some antioxidant enzymes activities of female Wistar rats administered combined oral contraceptives

In this study, the effects of vitamin E and folic acid on the superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA) production and glutathione-S-transferase (GST) activities in female wistar rats treated with combined oral contraceptives (COC) containing ethinyl estradiol in combination with levonorgestrel were determined. Twenty female rats were divided into four groups: group A (control) received distilled water; group B received combined oral contraceptives (COC) for 15 days with a dosage of 0.667 mg/kg body weight/day; group C received combined oral contraceptive and vitamin E (0.667 mg/kg body weight COC + 15 mg/kg body weight of vitamin E/day) for 15 days and group D received combined oral contraceptives and folic acid (0.667 mg/kg body weight of COC + 1 mg/kg body weight/day) for 15 days. Administration of vitamin E and folic acid caused significant decrease (P 0.05) in catalase level. In addition, administration of vitamin E and folic acid caused significant decrease (P < 0.05) in malondialdehyde (MDA) concentration by 21 and 11% respectively. Administration of vitamin E and folic acid caused significant decrease (P < 0.05) in glutathione-S-transferase by 39 and 23%, respectively. Key words: Combined oral contraceptives, vitamin E, folic acid, antioxidant enzymes.

Clinical Study on the Low-Dose Norgestrel Ethinyl Estradiol Combination as An oral Contraceptive.

A low dose of oral contraceptive, containing 0.5 mg norgestrel and 0.05 mg ethinyl estradiol, was given daily tc 303 women for a total of 5,159 cycles in order to study its efficacy and acceptability as an oral contraceptive agent. Only one pregnancy occurred. The cycle length was markedly stabilized, and the duration of bleeding was shortened and 88.5% of the treated cycles were 3 to 5 davs. Breadthrough bleeding and amenorrhea occurred rarely during the cycles under medication. Main side effects observed were gastro-intestinal symptoms and weight gain. The gastro-intestinal symptoms were more frequent in the first 3 cycles, but gradually decreased in later cycles, showing good tolerance of the drug, while the weight gain occurred in 4.2% of 303 women. In the liver function tests employed, abnormalities in BSP retention, serum transaminase values or TTT were recorded in a limited number of cases. However, neither jaundice nor thrombophlebitis was observed in any cases treated, while hypertension occurred in 4 cases. The drug investigated can be evaluated as acceptable to most women seeking contraception.

Ethinylestradiol/Dienogest in Oral Contraception

The low-dose combined oral contraceptive of ethinylestradiol 30 microg and dienogest 2 mg was launched in Germany in 1995, and is now the most commonly prescribed oral contraceptive in this country. Dienogest is a novel 19-nortestosterone-derived progestin with a unique pharmacokinetic and pharmacological profile, including antiandrogenic properties. Clinical studies have demonstrated that ethinylestradiol/dienogest is a reliable ovulation inhibitor with high contraceptive efficacy that is comparable with other combined oral contraceptives. It also provides effective cycle control, with reduced intensity and duration of menstrual bleeding, and improves dysmenorrhoea. The combination of ethinylestradiol and dienogest reduces serum androgen levels, and increases the levels of thyroid hormones; however, although thyroid hormone levels increase, there is no increased activity due to increases in transporter protein. Like other low-dose oral contraceptives, ethinylestradiol/dienogest has only minor influences on lipid and carbohydrate metabolism, adrenal hormones and blood pressure parameters, and appears to have a balanced effect on the haemostatic system. Ethinylestradiol/dienogest also has beneficial effects on hair and skin; a number of studies have reported decreased hair and skin greasiness, and improvements in acne vulgaris following treatment with ethinylestradiol/dienogest. After discontinuation of ethinylestradiol/dienogest, there may be a small delay in conception during the first three cycles, but there is no subsequent impairment of fertility. Furthermore, the duration of use of ethinylestradiol/dienogest does not seem to influence the rate of conception or time to conception. Ethinylestradiol/dienogest is well tolerated; adverse reactions associated with treatment include breast pain, headache and nausea/vomiting. These adverse reactions are rare and decrease in incidence over time.

Hormonelle Antiandrogene in der Aknetherapie

An enhanced sebaceous gland activity with production of proinflammtory sebaceous lipids belongs to the major pathogenetic factors of acne. Hormonal antiandrogen treatment targets the androgen-metabolizing cells of the pilosebaceous unit, i. e. follicular kertinocytes and sebocytes, and leads to sebostasis, with a reduction of the sebum secretion rate of 12.5 to 65 %. Concerning their mechanism of action, hormonal antiandrogens are classified in androgen receptor blockers, inhibitors of circulating androgens by affecting the ovarial function (oral contraceptives), inhibitors of circulating androgens by affecting the pituitary (gonadotrophin-releasing hormone agonists and dopamin agonists in hyperprolactinemia), inhibitors of the adrenal function, and inhibitors of peripheral androgen metabolism (5-reductase inhibitors, inhibitors of other enzymes). In this study, all original and review publications on hormonal antiandrogen treatment of acne as monotherapy or in combination included in MEDLINE, EMBASE and COCHRANE libraries were extracted by using the terms "acne", "seborrhea", "polycystic ovary syndrome", "hyperandrog*" and "treatment" and classified according to their level of evidence. Antiandrogen treatment is overall active on acne lesions. The combinations of ethinyl estradiol with cyproterone acetate chlormadinone acetate, dienogest desogestrel and drospirenone have shown the strongest antiacne activity. Gestagens or estrogens as monotherapy, spironolactone, flutamide, gonadotrophin-releasing hormone agonists and inhibitors of peripheral androgen metabolism are not recommended according to the current stand of knowledge. Low dose prednisolone is to only be administered at late onset congenital adrenal hyperplasia and dopamine agonists at hyperprolactinemia. Treatment with hormonal antiandrogens requires missing of any contraindications. Hormonal antiandrogen treatment is limited to female patients who present additional signs of peripheral hyperandrogenism or hyperandrogenemia. In addition, females with acne tarda, persistent acne recalcitrant to treatment, with parallel wish of contraception, and as a requirement for a systemic isotretinoin treatment can be treated with hormonal antiandrogens. Hormonal antiandrogen treatment is not a primary monotherapy for uncomplicated acne.

Bleeding patterns and menstrual-related symptoms with the continuous use of a contraceptive combination of ethinylestradiol and drospirenone: a randomized study

Background The objective of this study was to compare bleeding patterns of women using a contraceptive combination of 30 mcg ethinylestradiol (EE) and 3 mg drospirenone (DRSP) continuously or cyclically. Menstrual-related symptoms were also evaluated. Study Design This open, prospective, randomized study evaluated 78 women using the EE/DRSP combination continuously for 168 days or for six 28-day cycles, each followed by a 7-day hormone-free interval. A diary with pre-established scales was used to assess the frequency and intensity of bleeding and menstrual-related symptoms. Results Amenorrhea increased with continuous use; 62.2% of women with continuous use were amenorrheic at the end of treatment (95% CI: 46.6–77.8%). Dysmenorrhea, headache, acne, nausea, edema and increased appetite improved significantly in the continuous-use group, and mastalgia and edema in the cyclic-use group (p<.05). Six subjects in the continuous-use group (15.4%) and three in the cyclic-use group (7.7%) discontinued due to adverse events. Conclusions Continuous use was associated with amenorrhea and fewer menstrual-related symptoms compared to cyclic use.

Epidemiological and clinical aspects of migraine in users of combined oral contraceptives

Background Migraine was assessed in users of combined oral contraceptives (COCs). Study Design This study had a cross-sectional design. Women with headaches were evaluated according to International Headache Society criteria and subsequently allocated to a “migraine” or “non-migraine” group. Results Migraine was detected in 80/480 women (16.6%), while other types of headache not classified as migraine were observed in 400 women (83.4%). Following COC use, headaches worsened in 32.5% and 19.3% [odds ratio (OR)=3.02; 95% confidence interval (CI)=1.68–5.4] and improved in 30% and 13.8% (OR=3.9; 95% CI=2.12–7.18) of the “migraine” and “non-migraine” groups, respectively. In the migraine group only, headache episodes occurred predominantly during or around the hormone-free interval (OR=2.05; 95% CI=1.26–3.35). The combination of ethinylestradiol (EE) and drospirenone (DRS) was significantly associated with an improvement in the frequency and/or intensity of migraine-type headaches, compared with other types of COCs. Conclusions The prevalence of migraine in COC users appears similar to that found in the general population. Migraines, but not other types of headache, were significantly affected by COCs. The EE/DRS combination was associated with a greater likelihood of improvement in migraine compared with other types of COCs.

Effect of a continuous regimen of contraceptive combination of ethinylestradiol and drospirenone on lipid, carbohydrate and coagulation profiles

Background The objective of this study was to evaluate the effects of a contraceptive pill containing ethinylestradiol (30 mcg) and drospirenone (3 mg) in a continuous regimen on lipid, carbohydrate and coagulation parameters. Study Design This open, prospective, randomized study included 78 participants (mean age 27.8 years) who were randomized into two groups to use the pill continuously for 168 days or for six 28-day cycles with a 7-day hormone-free interval between cycles. Markers of lipid, carbohydrate and coagulation profiles were measured prior to initiation and after the 6 months of pill use. Results No statistically significant differences were found between the two contraceptive regimens with respect to carbohydrate or lipid profiles or in the parameters related to coagulation. Conclusions The contraceptive combination of ethinylestradiol and drospirenone used in a continuous regimen was associated with metabolic alterations similar to those found during the traditional cyclic regimen of oral contraceptive use.

Effects of oral contraception with ethinylestradiol and drospirenone on oxidative stress in women 18–35 years old

Background Oral contraceptives (OCs) with estrogens and progestins may affect oxidative stress (OS) status. Study design A group of 32 women using oral contraceptives (OCU) containing 0.03 mg ethinylestradiol and 3 mg drospirenone have been compared to a matched control group of 30 noncontraception users (NCU). Blood levels of antioxidants, trace elements and markers of lipid peroxidation were assessed by biochemical methods. A microarray analysis of whole blood mRNA levels of 200 genes involved in OS-dependant pathway was also performed. Results Levels of zinc, vitamin E and antibodies to oxidized low-density lipoproteins (LDLs) were not significantly different between the two groups. On the other hand, significant increases in the mean levels of lipid peroxides (+176%, p<.001), oxidized LDLs (+145%, p<.002), copper (+103%, p<.001), Cu/Zn ratio (+100%, p<.001) and a significant decrease in the mean level of β-carotene (−41%, p<.01) were observed in the OCU compared to NCU. There was a highly significant positive correlation between the lipid peroxide levels and the copper-to-zinc ratio. From the 200 genes tested by microarray, one coding for HSP70 was significantly up-regulated (log 2 fold change=+ 0.45, p<.02) and one coding for inducible nitric oxide synthase significantly down-regulated (log 2 fold change=−0.24, p<.05) in the OCU compared to the NCU. Conclusions The recently introduced combination of ethinylestradiol and drospirenone induced the heightening of lipid peroxidation correlated with high levels of copper, a situation that could be associated with increased cardiovascular risk.

Oral contraceptive administration aggravates nitric oxide synthesis inhibition-induced high blood pressure in female rats

The use of estrogen–progestogen oral contraceptive (OC) is associated with high blood pressure, although mechanisms responsible are still unclear. This study sought to investigate the effects of administration of OC on high blood pressure resulting from nitric oxide (NO) synthesis inhibition in female Sprague– Dawley rats. Rats were given ethinyl estradiol in combination with norgestrel and were treated with NO synthase inhibitor, N G-nitro- l-arginine methyl ester ( l-NAME) in the drinking water or drinking water alone for 6 weeks. OC treatment alone led to a significant increase in blood pressure and positive water balance. Treatment with l-NAME alone resulted in a significant elevation of blood pressure without significant positive water balance. Concomitant treatment with OC and l-NAME produced significant increases in blood pressure and water balance. These magnitudes of increases were significantly greater than those observed in rats treated with OC or l-NAME alone. Treatment with OC did not affect NO biosynthesis with or without concurrent l-NAME treatment. Treatment with OC and/or l-NAME did not significantly affect body weight, food intake, heart rate, cardiac weight/body weight ratio, plasma sodium, glomerular filtration rate and urinary sodium output. Conclusion: These data demonstrate that OC administration resulted in a modest increased blood pressure via enhanced water retention that was not associated with impaired NO synthesis. On the other hand, these results showed that increased blood pressure induced by inhibition of NO synthesis was not associated with water retention. The study also indicated that OC administration aggravated increase in blood pressure during NO synthesis inhibition, via enhanced water retention.

Novel ethinyl estradiol-beta-cyclodextrin clathrate formulation does not influence the relative bioavailability of ethinyl estradiol or coadministered drospirenone

Background A new combined oral contraceptive formulation has been developed consisting of a beta-cyclodextrin (betadex) clathrate formulation of ethinyl estradiol in combination with drospirenone (EE-betadex clathrate/drsp). In this novel EE-betadex clathrate/drsp preparation, betadex serves as an inert complexing agent to enhance stability and shelf-life. The study was conducted to investigate the relative bioavailability and pharmacokinetic parameters of EE and drsp after oral administration of EE-betadex clathrate/drsp. Methods This was an open-label, randomized, single-dose, three-period, three-treatment, crossover study conducted in 18 healthy postmenopausal women aged 45–75 years. The women received single oral doses of 40 mcg EE/6 mg drsp formulated as EE-betadex clathrate/drsp or EE/drsp (EE as a free steroid) tablets, or as a microcrystalline suspension on three separate occasions. Serum samples were collected for pharmacokinetic analyses. Results The relative bioavailability of EE and drsp after EE-betadex clathrate/drsp tablet administration was comparable with that achieved with the EE/drsp tablet (107% and 101%, respectively). In addition, the inclusion of EE in a betadex clathrate does not affect the pharmacokinetics of either EE or drsp. There were no safety concerns with any of the medications. Conclusion The betadex clathrate formulation of EE, when combined with DRSP, does not affect the pharmacokinetics and relative bioavailability of either EE or drsp.

Study of low-density lipoprotein receptor regulation by oral (steroid) contraceptives: desogestrel, levonorgestrel and ethinyl estradiol in JEG-3 cell line and placental tissue

Background The aim of this study was to compare in vitro the role of two oral contraceptives, desogestrel (a less androgenic derivative of levonorgestrel) and levonorgestrel — alone and in combination with ethinyl estradiol — on low-density lipoprotein (LDL) receptor regulation by assessing receptor protein expression and functional effectiveness. Study Design Placental tissue and cultured placental cells (JEG-3) were used to study the expression and endocytotic activity of LDL receptor protein. The expression of the receptor was assessed by immunocytochemistry and immunoblot assays with and without contraceptive challenge. Functioning activity of LDL receptor was studied by measuring the rate of uptake of LDL by placental cells. Quantification of LDL was based on the total cholesterol content of the lipoprotein. Results A combination of desogestrel (20 ng/mL of incubation medium) and ethinyl estradiol (10 ng/mL of incubation medium) maintained the LDL receptor at high level of expression and functioning mode. In contrast, the double-blind preparation of levonorgestrel (20 ng/mL) and ethinyl estradiol (10 ng/mL) had shown much lower expression as well as receptor-mediated LDL uptake. The concentration of contraceptives used in this study was similar to the prevailing concentration of oral contraceptives in clinical use. Conclusion Higher expression of LDL receptor and enhanced rate of LDL uptake by the receptor protein projects the possibility that there might be less atherosclerosis-related disorders from the combination of desogestrol and ethinyl estradiol.

Genes Linked to Mood Symptoms of Premenstrual Dysphoric Disorder

Genes Linked to Mood Symptoms of Premenstrual Dysphoric Disorder

Comparison of Somatic Embryogenesis in Medicago sativa and Medicago truncatula

In this study, the regeneration through embryogenesis of two species of Medicago were studied. Seeds of Medicago sativa cv. Rehnani and M. truncatula line A17 were grown on MS medium. After 4-6 weeks, segments of leaf and stem from two species were transferred to MS medium containing 2 mg L(-1) NAA, 2,4-D and Kinetin. The results indicated that callus formation from leaf explants of M. sativa was higher than M. trancatula. In the next stage, media with different combinations of auxin, cytokinin or ethinyl estradiol were provided for regeneration. Then in two stages, explants of leaf and stem of two species were transferred on these media. Results after 3-6 weeks showed that in medium containing NAA and TDZ, stem pieces ofM. sativa produced shoots while leaf pieces on NAA and ethinyl estradiol formed roots. Leaf explants of M. truncatula in the medium containing NAA and BAP, produced somatic embryos. Also in media with auxin and ethinyl estradiol, somatic embryos were formed on calli of two species. Ethinyl estradiol and auxin together can induce somatic embryogenesis and root production on calli and stem or leaf explants.