Pharmacology and Toxicology of Ethinyl Estradiol and Norethindrone Acetate in Experimental Animals

Maier, William C.; Herman, James R.

doi:10.1006/rtph.2001.1483

Cited by 24 publications

(19 citation statements)

References 62 publications

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“…EE 2 is a synthetic estrogen used in many oral contraceptive formulations and hormone replacement therapies (Maier & Herman, 2001). The presence of these estrogens in Canadian STPs has been documented with median concentrations of 9 ng/L for EE 2 and 6 ng/L for E 2 (Ternes et al, 1999).…”

mentioning

confidence: 99%

Exposures to Estradiol, Ethinylestradiol and Octylphenol Affect Survival and Growth ofRana pipiens and Rana sylvaticaTadpoles

Hogan

Lean

Trudeau

2006

Journal of Toxicology and Environmental Health, Part A

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Endocrine disrupting compounds (EDCs) are often detected in the aquatic environment and can negatively affect the health of wildlife populations. However, little is known about the sensitivity of native amphibians to EDCs. Wood frogs (Rana sylvatica) and Northern leopard frogs (Rana pipiens) were exposed to three estrogenic EDCs: estradiol (E2), ethinylestradiol (EE2), and 4-tert-octylphenol (OP). In addition, R. pipiens were exposed during two developmental stages (Gosner stages 26 and 36) to examine life-stage differences in sensitivity. Tadpoles were exposed for 2 wk to 8 nominal concentrations (0.25 microM-10 microM) of each compound. Individual mortality was recorded during the exposure period, while body weight was measured at the end of 2 wk. LC50 values were calculated, and differences in body weight between vehicle control and exposed groups were assessed. Rank order toxicity of the compounds for both R. pipiens stages and both species was OP > EE2 > E2. Gosner stage 26 tadpoles were more sensitive (LC50: E2 [5.57 microM], EE2 [3.01 microM], OP [1.36 microM]) to all three compounds when compared to stage 36 tadpoles (LC50: E2 [>10 microM], EE2 [4.17 microM], OP [2.80 microM]). Interspecies comparisons revealed R. sylvatica tadpoles (LC50: E2 [2.50 microM], EE2 [1.89 microM], OP [0.74 microM]) as being more sensitive to the three compounds than R. pipiens (LC50: E2 [4.56 microM], EE2 [2.75 microM], OP [1.42 microM]). Xenoestrogen exposure also affected tadpole body weight which may have long-term adverse effects on the rate of metamorphosis. These results provide toxicological data needed for assessing sublethal effects of estrogenic compounds on amphibian development and suggest that environmental levels of OP may pose a serious risk to the health of amphibian populations.

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confidence: 99%

Exposures to Estradiol, Ethinylestradiol and Octylphenol Affect Survival and Growth ofRana pipiens and Rana sylvaticaTadpoles

Hogan

Lean

Trudeau

2006

Journal of Toxicology and Environmental Health, Part A

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“…Dogs are more sensitive to estrogen and progestins than humans. The optimal estrogen : progesterone ratio for dogs is approximately 1 : 1,000–1 : 3,000 17 . Bone marrow toxicity is the most common side effect of estrogen administration in the dog.…”

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confidence: 99%

Hormone Therapy for Treatment of Colonic Vascular Ectasia in 2 Dogs

Goldman

Parnell

Holland

2008

Veterinary Internal Medicne

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ase History 1: A 10-year-old sexually intact male mixed breed dog was examined because of a 5-year history of intermittent melena, hematochezia, and a chronic microcytic anemia. In the 5 months before examination, the hemorrhagic episodes had increased in frequency and intensity, requiring 3 whole blood transfusions for stabilization. On physical exam, a grade III/ VI left apical systolic murmur was ausculted. Physical examination also revealed tachycardia, tachypnea, and pale mucous membranes. Rectal examination revealed evidence of melena and hematochezia. CBC results revealed a severe microcytic (MCV 59 fl; reference range 60-75 fl), normochromic (MCHC 33 g/ dL; reference range 32-36 g/dL) anemia (HCT, 12.5%; reference range 37-55%) with poor evidence of regeneration (reticulocyte count 54,000; reference range 460,000) and a total protein of 4.5 g/dL (reference range; 6.0-8.0 g/dL). Red blood cell (RBC) morphology was characterized by a 1 1 anisocytosis, polychromasia, and Howell Jolly bodies. The remainder of the clinicopathologic results was unremarkable as were results of diagnostic imaging.A crossmatch was performed and a packed-RBC transfusion (12 mL/kg [5.6 mL/lb]) was administered. PCV and total solids improved after the transfusion to 22% and 8.0 g/dL, respectively. The tachypnea, tachycardia, and murmur resolved after administration of the transfusion.Endoscopic evaluation revealed a small gastric ulcer and a friable, hyperemic duodenal mucosa. Colonoscopy revealed multiple bundles of tortuous, dilated vessels, which were found diffusely throughout the length of the colon.A diagnosis of colonic vascular ectasia was made from the characteristic gross morphologic abnormalities visualized during endoscopy. The diffuse distribution and number of vascular lesions made laser coagulation or electrocautery an inappropriate method of treatment. Subtotal colectomy was considered as an option for treatment, but hormone therapy alone was eventually chosen because of the owner's desire to avoid the potential morbidity associated with surgery. The prednisone and azathioprine therapy was tapered and discontinued and hormone therapy was initiated.Diethylstilbestrol (DES) was instituted at 0.33 mg/kg (0.15 mg/lb), PO q24h, then tapered to twice weekly after a 5-day loading period. The bleeding episodes decreased in severity over the next 3 weeks, but did not resolve, and the dog was administered an additional transfusion of packed-RBCs (12 mL/kg [5.6 mL/lb]). Altrenogest a (a synthetic progestin) was added to the twice weekly estrogen therapy at 0.04 mg/kg (0.02 mg/lb), PO q24h, for 7 days, and then increased to 0.08 mg/kg (0.04 mg/lb), PO q24h. Once the combination estrogen-progesterone therapy had been initiated, the dog improved clinically. Any significant hemorrhage subsided in approximately 1 week and the PCV stabilized between 35 and 40%. Over the next several weeks the microcytosis resolved. One episode of melena and hematochezia occurred 7 months later, after Dog 1 was treated with prednisone and carprofen by...

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“…Most studies of LNG-EC are concerned with conception efficiency and side effects and include only limited data regarding the outcome of the infants. LNG-EC is considered to have no effects on the developing fetus, if the contraceptive fails and pregnancy occurs [1,[8][9][10][11][12][13][14], and the only retrospective cohort study specifically examining the effects of LNG-EC on the fetus in cases of contraceptive failure found no differences in neonatal outcomes between 36 women who were exposed to LNG and 80 control women [17]. In China, however, many gynecologists have doubts about the safety of EC in the event of a subsequent pregnancy.…”

Section: Discussionmentioning

confidence: 99%

“…Although LNG-EC is considered to have no effects on the developing fetus if the contraceptive fails and pregnancy occurs [2,[8][9][10][11][12][13][14], there have been a few studies specifically examining this issue. Some animal studies have indicated a dose-dependent virilization of female fetuses related to LNG's androgenic characteristics [15,16], and human studies have indicated that progestins can exert masculinizing effects on female fetuses, but exposure during the eighth to 10th weeks of gestation and high doses are required [8].…”

Section: Introductionmentioning

confidence: 99%

Physical and Mental Development of Children after Levonorgestrel Emergency Contraception Exposure: A Follow-Up Prospective Cohort Study1

Zhang

Wen

et al. 2014

Biology of Reproduction

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Levonorgestrel (LNG), a dedicated emergency contraception (EC) product, has been available over-the-counter in China for more than 14 yr. Although LNG-EC is considered to have no effects on the developing fetus if the contraceptive fails and pregnancy occurs, there have been a few studies specifically examining this issue. The purpose of this study was to compare the physical and mental development of children born after LNG-EC failure with that of a cohort of children born to mothers with no history of exposure to LNG or any teratogenic substances. A group of 195 children who were exposed to LNG-EC during their mothers' conception cycle (study group) were matched to a group of 214 children without exposure to LNG (control group). The physical and mental development of the children were evaluated and compared over a 2-yr period. There were four congenital malformations in the study group and three in the control group (2.1% vs. 1.4%, respectively, P > 0.05). Over the 2-yr follow-up period, there were no statistically significant differences between the two groups with respect to children's weight, height, head circumference, and intelligence scores, and the values of all parameters of both groups were similar to those of the national standards. In summary, LNG-EC has no effect on the physical growth, mental development, or occurrence of birth defects in children born from pregnancies in which EC failed.

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Pharmacology and Toxicology of Ethinyl Estradiol and Norethindrone Acetate in Experimental Animals

Cited by 24 publications

References 62 publications

Exposures to Estradiol, Ethinylestradiol and Octylphenol Affect Survival and Growth ofRana pipiens and Rana sylvaticaTadpoles

Exposures to Estradiol, Ethinylestradiol and Octylphenol Affect Survival and Growth ofRana pipiens and Rana sylvaticaTadpoles

Hormone Therapy for Treatment of Colonic Vascular Ectasia in 2 Dogs

Physical and Mental Development of Children after Levonorgestrel Emergency Contraception Exposure: A Follow-Up Prospective Cohort Study1

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