This record contains information specific to ethinyl estradiol used alone. Users with an interest in an oral contraceptive should consult the record entitled, "Contraceptives, Oral, Combined." There is little information available on the use of ethinyl estradiol alone during breastfeeding. Levels in milk appear to be low. Based on studies on oral contraceptives that contain ethinyl estradiol, immediate side effects such as breast enlargement appear to occur rarely. It seems likely that doses of 30 mcg daily or greater can suppress lactation. The magnitude of the effect on lactation likely depends on the dose and the time of introduction postpartum, but data are not adequate to accurately define these doses and times.

This record contains information specific to oral levonorgestrel used alone for contraception. Those with an interest in a combination oral contraceptive should consult the record entitled, Contraceptives, Oral, Combined. Although nonhormonal methods are preferred during breastfeeding, progestin-only contraceptives such as levonorgestrel are considered the hormonal contraceptives of choice during lactation. Fair quality evidence indicates that levonorgestrel does not adversely affect the composition of milk, the growth and development of the infant or the milk supply. Expert opinion holds that the risks of progestin-only contraceptive products usually are acceptable for nursing mothers at any time postpartum.[1,2] Some evidence indicates that progestin-only contraceptives may offer protection against bone mineral density loss during lactation, or at least do not exacerbate it.[3-5] A large percentage of women who planned to breastfeed discontinued oral progestin-only contraceptives by 3 months postpartum[6] and progestin-only contraceptives often result in rapid repeat pregnancy in the absence of breastfeeding.[7] Postcoital levonorgestrel appears to have no long-term adverse effects on breastfeeding or the infant.[8-11]

The objective of the study was to evaluate the sexual function and quality of life (QoL) of healthy women on a new contraceptive vaginal ring (CVR) containing ethinylestradiol (EE) 3.47 mg and etonogestrel (ENG) 11.00 mg (study group) manufactured with a new polymer composition compared to EE 2.7 mg/ENG11.7 mg CVR (control group). Fifty-eight women were randomly allocated to the study group and the control group. The Female Sexual Function Index (FSFI), the Female Sexual Distress Scale (FSDS) and the Short Form-36, were used to assess sexual function, sexual distress and QoL, respectively. The study included two follow-ups, at 90 days and at 180 days. The control group reported more adverse events, mainly breakthrough bleeding, than the study group. The sexual function scores in the women in the study group improved with respect to those of the control group both at the 1st (FSFI, p = .009; FSDS, p = .001) and at the 2nd (FSFI, p = .001; FSDS, p = .002) follow-up. QoL of the study group improved at the 1st follow-up (p < .05) and 2nd (p < .01) follow-up. The control group improved their QoL at the 2nd follow-up (p < .01). The more gradual EE release of the new polymer composition could justify the behavioral differences of the women of the two groups.

Combined oral contraceptive (COC) use is associated with increased risk of developing hypertension. Activation of the intrarenal renin-angiotensin system (RAS) and endothelial dysfunction play an important role in the development of hypertension. We tested the hypothesis that COC causes hypertension that is associated with endothelial dysfunction and upregulation of intrarenal angiotensin-converting enzyme 1 (Ace1) and angiotensin II type 1 receptor (At1r). Female Sprague-Dawley rats aged 12 weeks received (p.o.) olive oil (control) and a combination of 0.1 μg ethinylestradiol and 1.0 μg norgestrel (low COC) or 1.0 μg ethinylestradiol and 10.0 μg norgestrel (high COC) daily for 6 weeks. Blood pressure was recorded by tail cuff plethysmography. Expression of genes in kidney cortex was determined by quantitative real-time polymerase chain reaction. COC treatment led to increased blood pressure, circulating uric acid, C-reactive protein and plasminogen activator inhibitor-1, renal uric acid, and expression of renal Ace1 and At1r. COC treatment resulted in increased contractile responses to phenylephrine in endothelium-denuded aortic rings. Endothelium-dependent relaxation responses to acetylcholine, but not endothelium-independent relaxation responses to nitric oxide (NO) donation by sodium nitroprusside, were attenuated in COC-exposed rings. Impaired relaxation responses to acetylcholine were masked by the presence of NO synthase inhibitor (L-NAME) in the COC-exposed rings, whereas the responses to acetylcholine in the presence of selective cyclooxygenase-2 inhibitor (NS-398) were enhanced. These findings indicate that COC induces hypertension that is accompanied by endothelial dysfunction, upregulated intrarenal Ace1 and At1r expression, and elevated proinflammatory biomarkers.

Thrombotic microangiopathy (TMA) after kidney transplantation has various aetiologies, including acute antibody-mediated rejection, bacterial or viral infection and immunosuppressive drugs, particularly calcineurin inhibitors. We present the case of a 28-year-old woman who developed TMA 30 months after the transplantation of an ABO-incompatible kidney from a living unrelated donor. The patient developed a sudden onset of allograft renal dysfunction and became uremic. She was transferred to our institution from a community hospital with strongly suspected acute allograft rejection. Intensive treatments for both T- and B-cell mediated acute rejection, including steroid pulse therapy, double-filtration plasmapheresis, antithymocyte globulin (1.5 mg/kg × 14 days) and rituximab (100 mg), were initiated during haemodialysis. However, her renal allograft function did not improve. Histopathological analysis 8 days after the treatment indicated TMA, despite the absence of apparent acute T-cell- or acute antibody-mediated rejection. There were no symptoms of infectious diseases, such as intestinal haemorrhagic colitis or viral infection. We concluded that the use of oral contraceptives, which had been initiated 3 weeks before TMA onset for the treatment of irregular vaginal bleeding, was the aetiologic agent.

Hidradenitis suppurativa (HS) is a chronic, inflammatory, recurrent, debilitating skin disease. Several treatment modalities are available, but most of them lack high-quality evidence. A systematic search was performed to identify all randomized controlled trials for the treatment of HS in order to review and evaluate the evidence. Recommendations for future randomized controlled trials include using validated scores, inclusion of patient rated outcomes, and thorough report of side effects. Evidence for long-term treatment and benefit/risk ratio of available treatment modalities is needed in order to enhance evidence-based treatment in daily clinical practice. Combining surgery with antiinflammatory treatment warrants further investigation.

To evaluate the effect of feeding thermally oxidized vegetable oils and animal fats on growth performance, liver gene expression, and liver and serum fatty acid and cholesterol concentration in young pigs, 102 barrows (6.67 ± 0.03 kg BW) were divided into 3 groups and randomly assigned to dietary treatments in a 4 × 3 factorial arrangement. The main factors were lipid source (n = 4; corn oil [CN], canola oil [CA], poultry fat [PF], and tallow [TL]) and lipid peroxidation level (n = 3; original lipids [OL], slow oxidation [SO] through heating at 95°C for 72 h, or rapid oxidation [RO] through heating at 185°C for 7 h). Pigs were provided ad libitum access to diets in group pens for 28 d followed by controlled feed intake in metabolism crates for 10 d. On d 39, all pigs were euthanized for liver samples to determine liver weight, lipid profile, and gene expression patterns. Lipid oxidation analysis indicated that compared with the OL, SO and RO of lipids had a markedly increased concentrations of primary and secondary peroxidation products, and the increased lipid peroxidation products in CN and CA were greater than those in PF and TL. After a 28-d ad libitum feeding period, pigs fed RO lipids tended to have reduced ADFI (P = 0.09) and ADG (P < 0.05) compared with pigs fed OL, and pigs fed CA had reduced G:F (P < 0.05) compared with pigs fed all other lipids. Pigs fed RO lipids tended to have increased relative liver weight (P = 0.09) compared with pigs fed OL. Liver triglyceride concentration (LTG) in pigs fed OL was greater (P < 0.05) than in pigs fed SO lipids and tended to be greater (P < 0.07) than in pigs fed SO. The reduced LTG were consistent with increased (P < 0.05) mRNA expression of PPARα factor target genes (acyl-CoA oxidase, carnitine palmitoyltransferase 1, and mitochondrial 3-hydroxy-3-methylglutary-CoA synthase) in pigs fed SO and RO lipids compared with pigs fed OL. Pigs fed CN or CA tended to have increased LTG (P = 0.09) compared with pigs fed TL. Liver cholesterol concentration in pigs fed CN was less (P < 0.05) than in pigs fed PF and tended to be less (P = 0.06) than in pigs fed TL, whereas pigs fed CA had a reduced (P < 0.05) liver cholesterol compared with pigs fed PF or TL. In conclusion, feeding thermally oxidized lipids negatively affected growth performance and LTG of young pigs, which was associated with an upregulation of fatty acid catabolism pathways.

Oral contraceptives (OC) may cause intrahepatic cholestasis or increase a pre-established liver damage. OC effects on hepatic injury biochemical markers remain contradictory and the role of cytokines in those processes is fairly unknown. Two doses, simple or double, of the OC combination ethinylestradiol/norgestrel were administered during 14 or 28 days to normal and cholestatic female rats. Liver damage markers and the cytokines tumor necrosis factor-α (TNF-α), interleukin-10 (IL-10) and transforming growth factor-β (TGF-β) were determined in plasma and liver. OC caused ambiguous results on cholestasis indicators, even more in cholestatic rats. Necrosis rose during cholestasis while OC lowered it in normal rats. Fibrosis was induced by cholestasis but OC double dose or intake time diminished that. Cholestasis depleted glycogen while OC did not alter it. Double dose or time of administration of OC significantly elevated the lipid peroxidation. Cholestasis modified plasma and liver cytokines but OC remarkably altered them in normal and cholestatic animals. TNF-α as well as IL-10 were increased in both tissues by OC, such rise was higher in normal rats. TGF-β was augmented by OC and more in cholestatic rats receiving double dose. Thus, OC modified most liver injury markers in normal rats although more pronouncedly in cholestatic ones, as well as increased hepatic oxidative stress. Liver fibrosis was decreased and corroborated by histological analysis even when TGF-β is elevated by OC. OC strongly immunomodulate cytokines that mediate liver damage or worsen a prior hepatopathy; those processes are influenced by dose, administration time and OC formulation.

Quartette (levonorgestrel [LNG]/ethinyl estradiol [EE] and EE) is an ascending-dose, extended-regimen combined oral contraceptive (COC) that consists of a constant dose of LNG 150 µg on days 1 to 84 with EE 20 µg on days 1 to 42, 25 µg on days 43 to 63, 30 µg on days 64 to 84, and 10 µg of EE monotherapy on days 85 to 91. A population pharmacokinetic (PK) model for EE was developed using nonlinear mixed-effects modeling to characterize the PK profile of EE administered in Quartette and other extended-regimen LNG/EE COCs. Model-predicted plasma concentration-time profiles demonstrated a stepwise increase in systemic exposure to EE during the first 84 days of the cycle following each EE dose change. Lower concentrations of EE were noted during the final 7-day period of EE 10 µg. Gradual increases in EE seen with Quartette may decrease the incidence of unscheduled bleeding frequently observed during early cycles of extended-regimen COCs.