Maturitas 46S1 (2003) S7–S16
Classification and pharmacology of progestins
"Norethisterone is also named norethindrone and is
often used as norethisterone acetate (NETA). Both
compounds are rapidly absorbed from the gastrointestinal
tract. The bioavailability is about 64%, 36%
are bound to SHBG, 61% to serum albumin and 3%
are free in the circulation. The principal metabolite
is 5-alpha dihydro-norethisterone"
"19-Nortestosterone derivatives (estranes) Norethisterone = norethindrone, norethisterone acetate, lynestrenol, ethinodiol acetate, norethinodrel"
"The most significant upregulation of ERalpha-activity was found with norethisterone, norethinodrel and desogestrel. In contrast, ERbeta was markedly activated only by norgestrel and to a lesser extent
by norethisterone, norethinodrel and levonorgestrel."
"the estrogen activity of norethisterone, norgestrel and levonorgestrel is at least in part a consequence of their metabolism into the 3(alpha, beta) 5-alpha reduced derivatives by 5-beta reductase activity"
According to the above review, norethindrone acetate is not only estrogenic but also androgenic.
CLIMACTERIC 2005;8(Suppl 1):3–63
Pharmacology of estrogens and progestogens: influence of different routes of administration
"The effect on the serum levels of SHBG is negligible,
whereas the oral therapy with estradiol or CEE
causes a dose-dependent, pronounced increase.
The effect may be attenuated by the addition of
progestins with androgenic activity, e.g. norethisterone
(NET)"
"The 5alpha-dihydro-NET has a relatively high binding affinity to the androgen
receptor and may play a role in the androgenic activity of NET."
"A small proportion of the NET dose (0.35%) is aromatized to EE, and the concentration–time curve of EE suggest that is formed in the liver205,268. Using a (lower dose), the levels of EE are low and, in the presence of a natural estrogen, probably without clinical relevance268. Using (higher) doses, the EE peak levels are similar to those after ingestion of EE (Figure 14)"
EE= Ethinyl Estradiol, the estrogen contained in birth control pills and that increases risk of thrombosis far more than bio-identical estradiol.
"NET has no glucocorticoid or antimineralocorticoid activity, but a weak androgenic effect."
Contraception. 1998 Sep;58(3 Suppl):23S-27S; quiz 67S.
Uniqueness of oral contraceptive progestins.
Carr BR.
Department of Obstetrics and Gynecology, University of Texas
"classification of oral contraceptives according to their level of androgenicity. Under such a system, norgestimate, desogestrel, and norethindrone would fall into the low category. (...)while norgestrel, norethindrone acetate, and levonorgestrel would fall into the high androgenicity category."
While progesterone is devoid of any androgenic and estrogenic effects, norethindrone acetate appears to have both. Because its estrogenic effects seem to partly come from its conversion to EE, an estrogen that is known to increase health risks, this is not a good thing. Its androgenic actions are, at best, weak and may be stronger, probably depending on dose used. Overall, not a good progestogen, in my opinion. I don't know why your doctor is so persistent on prescribing you progestins with androgenic activity and adverse effects on the cardiovascular system when there are progestogens that are much better for you, like bio-identical progesterone, dydrogesterone or 17alpha hydroxyprogesterone caproate.
