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Fetal programming
Published in Hung N. Winn, Frank A. Chervenak, Roberto Romero, Clinical Maternal-Fetal Medicine Online, 2021
Katherine E. Pelch, Jana L. Allison, Susan C. Nagel
Ethinyl estradiol is an orally active form of estradiol, and it is a component of OCPs. While ethinyl estradiol is not considered a teratogen, evidence from laboratory studies suggest that it is an endocrine disruptor. Millions of women use OCP, and approximately 2% to 5% will conceive while taking them due to noncompliance (116). Some of these women deliver infants exposed to 0.2 to 0.5 μg/kg of this potent estrogen during the critical window of sexual differentiation in the first trimester of pregnancy. This dose has been shown to alter mouse development (105,117). Additionally, ethinyl estradiol has been measured in waste water influent and effluent and may be a source of human exposure (118).
Endocrine Therapies
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
Diethylstilbestrol (DES) and ethinylestradiol are the main estrogenic agents in use for prostate cancer, and are described in detail below. However, it should be noted that they are not first-line treatments, and tend to be used in a palliative care setting when all other treatment strategies have failed. Both agents are associated with problematic side effects in men which are common and dose-related (e.g., venous and arterial thrombosis, nausea, fluid retention, feminization, impotency, and gynecomastia). In the past diethylstilbestrol has also been used to treat breast cancer in postmenopausal women but withdrawal bleeding, hypercalcemia and bone pain side effects can occur, and it is rarely used now for this purpose given the many more targeted therapies available. Ethinylestradiol is the most potent estrogenic agent available. Unlike other estrogens, it is metabolized slowly in the liver and so has a longer half-life.
Hidradenitis Suppurativa
Published in Peter Sagar, Andrew G. Hill, Charles H. Knowles, Stefan Post, Willem A. Bemelman, Patricia L. Roberts, Susan Galandiuk, John R.T. Monson, Michael R.B. Keighley, Norman S. Williams, Keighley & Williams’ Surgery of the Anus, Rectum and Colon, 2019
A significant percentage of women affected by HS have premenstrual flares, which suggests a role for hormone therapy in treating HS. Mortimer et al.9 conducted a randomised controlled trial of ethinyl estradiol and cyproterone acetate compared to ethinyl estradiol and norgestrel. Both treatments significantly reduced disease severity in affected patients. However, the rate of recurrence was high, long-term disease control was only achieved in 7 of 24 patients (29%) and there was significant dropout due to side effects or perceived lack of effect.9 Currently, there is no convincing evidence that hormonal therapy is efficacious in the long-term treatment of HS.
The influence of hormonal contraception on depression and female sexuality: a narrative review of the literature
Published in Gynecological Endocrinology, 2022
Laura Buggio, Giussy Barbara, Federica Facchin, Laura Ghezzi, Dhouha Dridi, Paolo Vercellini
Estrogens regulate synapse formation in multiple brain regions, including the hippocampus, prefrontal cortex and primary sensory-motor cortex [43]. Four natural estrogens exist in humans: estrone (E1), estradiol (E2), estriol (E3), and estetrol (E4). E2 is the most biologically active of the natural estrogens and the primary estrogen of the reproductive years. E1, the primary estrogen of menopause, results primarily from the conversion of adrenal androstenedione by aromatase in peripheral fat. Ethinyl estradiol (EE), the form of synthetic estrogen used in combined hormonal contraceptives, undergoes hepatic conjugation following oral administration, but unlike estradiol, it remains highly potent. EE is more biologically active compared to E2 and cannot be converted in E1 or other weaker estrogens [44].
The ins and outs of drug-releasing vaginal rings: a literature review of expulsions and removals
Published in Expert Opinion on Drug Delivery, 2020
Peter Boyd, Ruth Merkatz, Bruce Variano, R. Karl Malcolm
Planned temporary removal of a contraceptive ring releasing norethindrone and ethinyl estradiol has been investigated as part of a study to evaluate the effect of different initial insertion regimens on side effects (primarily transient post-insertion nausea and vomiting related to the initial high burst of ethinyl estradiol from the ring) [173]. In Regimen 1, subjects inserted the ring between 5 and 7 pm on the first day, removed it at bedtime, and then reinserted it the next morning. In Regimen 2, the ring was inserted between 5 and 7 pm and then left in place. In Regimen 3, the ring was inserted at bedtime between 10 pm and midnight. Thereafter, for all regimens, women left the ring in place for 3 weeks, removed it for 7 days, and reinserted it for a further three weeks according to the regimen to which they had been assigned. A new ring was used for each 2-month period. Differences in the incidence of side effects were not observed. Voluntary removals of the ring outside the initial insertion regiment were also reported, although this was mostly due to the different instructions given at the two centers regarding the removal of the ring for intercourse [174].
A technology evaluation of Annovera: a segesterone acetate and ethinyl estradiol vaginal ring used to prevent pregnancy for up to one year
Published in Expert Opinion on Drug Delivery, 2020
Elizabeth A. Micks, Jeffrey T. Jensen
Participants in the U.S. open-label Phase III trial were recruited at two sites for the Hepatic Factors Substudy [47]. Ethinyl estradiol is known to be a potent inducer of hepatic protein synthesis, including coagulation factors, which may be associated with the increased risk of VTE observed in users of combined hormonal contraceptives. Thrombotic biomarkers are often assessed in studies of hormonal contraceptives as indicators for VTE risk, but no studies have validated any biomarker as an actual surrogate for true VTE risk [48]. Over 13 cycles of use in 129 women enrolled in the sub-study, the SA/EE ring was associated with increased levels of SHBG, factor VIII, and fibrinogen, and decreased levels of protein S [47]. SHBG increased from 89.9 nmol/L at baseline to 187.2 nmol/L in cycle 13. In an analysis of only women switching from a different method of contraception containing EE (who had expected baseline elevations in hepatic proteins), only SHBG was noted to increase (mean increase of 28.4 nmol/L), and small declines in factor VIII and fibrinogen were noted with CVR use.