"Researchers say a hormone contraceptive injection for men is effective at preventing pregnancy â€“ but stopped their trial because of too many side effects.
Contraception for women was revolutionised with the Pill and other hormone base"...
Combination oral contraceptives act by suppression of gonadotropins. Although the primary mechanism of this action is inhibition of ovulation, other alterations include changes in the cervical mucus (which increase the difficulty of sperm entry into the uterus) and the endometrium (which reduce the likelihood of implantation).
The pharmacokinetics of norethindrone acetate and ethinyl estradiol tablets have not been characterized; however, the following pharmacokinetic information regarding norethindrone acetate and ethinyl estradiol is taken from the literature.
Norethindrone acetate appears to be completely and rapidly deacetylated to norethindrone after oral administration, since the disposition of norethindrone acetate is indistinguishable from that of orally administered norethindrone (1). Norethindrone acetate and ethinyl estradiol are subject to first-pass metabolism after oral dosing, resulting in an absolute bioavailability of approximately 64% for norethindrone and 43% for ethinyl estradiol (1-3).
Volume of distribution of norethindrone and ethinyl estradiol ranges from 2 to 4 L/kg (1-3). Plasma protein binding of both steroids is extensive ( > 95%); norethindrone binds to both albumin and sex hormone binding globulin, whereas ethinyl estradiol binds only to albumin (4).
Norethindrone undergoes extensive biotransformation, primarily via reduction, followed by sulfate and glucuronide conjugation. The majority of metabolites in the circulation are sulfates, with glucuronides accounting for most of the urinary metabolites (5). A small amount of norethindrone acetate is metabolically converted to ethinyl estradiol. Ethinyl estradiol is also extensively metabolized, both by oxidation and by conjugation with sulfate and glucuronide. Sulfates are the major circulating conjugates of ethinyl estradiol and glucuronides predominate in urine.
The primary oxidative metabolite is 2-hydroxy ethinyl estradiol, formed by the CYP3A4 isoform of cytochrome P450. Part of the first-pass metabolism of ethinyl estradiol is believed to occur in gastrointestinal mucosa. Ethinyl estradiol may undergo enterohepatic circulation (6).
Norethindrone and ethinyl estradiol are excreted in both urine and feces, primarily as metabolites (5,6). Plasma clearance values for norethindrone and ethinyl estradiol are similar (approximately 0.4 L/hr/kg) (1-3).
The effect of race on the disposition of norethindrone acetate and ethinyl estradiol tablets has not been evaluated.
The effect of renal disease on the disposition of norethindrone acetate and ethinyl estradiol tablets has not been evaluated. In premenopausal women with chronic renal failure undergoing peritoneal dialysis who received multiple doses of an oral contraceptive containing ethinyl estradiol and norethindrone, plasma ethinyl estradiol concentrations were higher and norethindrone concentrations were unchanged compared to concentrations in premenopausal women with normal renal function.
The effect of hepatic disease on the disposition of norethindrone acetate and ethinyl estradiol tablets has not been evaluated. However, ethinyl estradiol and norethindrone may be poorly metabolized in patients with impaired liver function.
Numerous drug-drug interactions have been reported for oral contraceptives. A summary of these is found under PRECAUTIONS, Drug Interactions.
2. Humpel M, Nieuwober B, Wendt H and Speck U: Investigations of pharmacokinetics of ethinyl estradiol to specific consideration of a possible first pass effect in women. Contraception 1979;19:421-432.
3. Back DJ, Breckenridge AM, Crawford FE, Maclver M, Orme MLâ€™E, Rowe PH and Watts MJ. An investigation of the pharmacokinetics of ethynylestradiol in women using radioimmunoassay. Contraception 1979;20:263-273.
4. Hammond GL, Lahteenmaki PLA, Lahteenmaki P and Luukkainen T. Distribution and percentages of non-protein bound contraceptive steroids in human serum. J Steriod Biochem 1982;17:375-380.
5. Fotherby K. Pharmacokinetics and metabolism of progestins in humans, in Pharmacology of the contraceptive steroids, Goldzieher JW, Fotherby K (eds), Raven Press, Ltd., New York, 1994, 99- 126.
6. Goldzieher JW. Pharmacokinetics and metabolism of ethynyl estrogens, in Pharmacology of the contraceptive steroids, Goldzieher JW, Fotherby K (eds), Raven Press Ltd., New York, 1994: 127- 151.
Last reviewed on RxList: 9/19/2016
This monograph has been modified to include the generic and brand name in many instances.
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