What does Diane 35 do? - Text Dump

Diane 35 is commonly prescribed for PCOS. It contains two ingredients

1. cyproterone 
2. ethinyl estradiol

Cyproterone  

Suppresses the actions of testosterone (and its metabolite dihydrotestosterone or DHT) on tissues. It acts by blocking androgen receptors which prevents androgens from binding to them and suppresses luteinizing hormone (which in turn reduces testosterone levels).

In addition, cyproterone acetate has weak progestational activity (i.e., it acts like progesterone) and can be used to treat hot flashes. As part of some combined oral contraceptive pills (Dianette in UK and Diane-35 in other countries) it decreases acne and hirsutism (male-pattern hair growth).


Pharmacology

Cyproterone acetate is a synthetic derivative of 17-hydroxyprogesterone, and acts as anandrogen receptor antagonist with weak progestational and glucocorticoid activity. Some portion is metabolized by hydrolysis to cyproterone and acetic acid.^[1] However, unlike many other steroid esters, cyproterone acetate is not extensively hydrolyzed, and much of its pharmacological activity is attributed to its acetate form.^[2] Cyproterone acetate has approximately three times the anti-androgenic activity of cyproterone.^[3]

Cyproterone acetate inhibits the steroidogenic enzyme 21-hydroxylase and to a lesser extent 3beta-hydroxysteroid dehydrogenase, both of which are needed to synthesize cortisol.^[4] The blockade of 21-hydroxylase can also result in reduced production of aldosterone, the primarymineralcorticoid hormone. Mutations in the gene encoding 21-hydroxylase are fairly common in the human population, therefore some patients may be affected more than others. Although cyproterone has some glucocorticoid activity,^[5] this is offset by the fact that cyproterone acetate inhibits cortisol production and can act as a competitive inhibitor of cortisol at the glucocorticoid receptor,^[6] thus its adrenosuppressive effects are usually fairly minor.^[7] However, since the glucocorticoid effects appear to be due to metabolites, rather than cyproterone acetate itself, the net effect may vary depending on the rate at which cyproterone acetate is metabolized.^[8] The progestational and glucocorticoid effects reduce production of gonadotropins, which usually results in lower testosterone levels, however the blockade of adrenal 21-hydroxylase results in the accumulation of androgen precursors which may be converted to testosterone, reducing the efficacy of the antiandrogen treatment. Due to the possibility of increased adrenal androgens, cyproterone acetate is sometimes combined with the 5-alpha-reductase inhibitor finasteride, and studies of hirsutism treatment show increased efficacy of this combination over cyproterone acetate alone.^[9] Some in vitro studies have suggested that cyproterone or cyproterone acetate may have a slight inhibitory effect on 5-alpha-reductase, however no significant reduction in DHT production has been observed in vivo.^[10]

Cyproterone acetate is metabolized by the CYP3A4 enzyme, forming the active metabolite 15β-hydroxycyproterone acetate, which retains its antiandrogen activity, but has reduced progestational activity.^[11][12][13] Therefore, use of cyproterone acetate in combination with substances which inhibit CYP3A4 may increase the progestational effects. Cyproterone acetate increases production of CYP3A4 by activating thepregnane x receptor.^[14]

^{Side Effects}

The most serious potential side effect is liver toxicity, and patients should be monitored for changes in liver enzymes, especially if taking a high dose (200–300 mg/day).^[2] Toxicity is dose-dependent and the low doses used in birth control pills (2 mg) do not appear to represent a significant risk.^[15]

Suppression of adrenal function and reduced response to ACTH have been reported. Low cortisol levels may impair carbohydrate metabolism, and patients with diabetes mellitus may require adjustments in insulin dosage. Low aldosterone levels may lead to salt loss andhyperkalemia (excess potassium). Patients taking cyproterone should have their cortisol levels and electrolytes monitored, and if hyperkalemia develops, reduce the consumption of food having a high potassium content.

Used alone, cyproterone acetate does not appear to have a significant effect on blood clotting factors, but in combination with ethinylestradiol(as in combined oral contraceptive pills) presents an increased risk of deep vein thrombosis.^[16] Women who take contraceptive pills containing cyproterone acetate have a six- to sevenfold risk of developing thromboembolism compared to women who do not take any contraceptive pill, and twice the risk of women who take a contraceptive pill containing levonorgestrel.^[17]

Cyproterone acetate is also associated with striae (stretch mark) formation, due to its glucocorticoid activity and drying of the skin.^[18]

Cyproterone has been associated with depressive mood changes in some patients, presumably due to androgen deprivation. However, others have reported significant antidepressant effects.^[19] This may be due to its effect on adrenal hormones, as similar antidepressant effects have been observed with other adrenal suppressants, such as metyrapone.^[20]

Cyproterone acetate suppresses production of estrogen due to its antigonadotrophic effect, and long-term use without estrogen replacement may result in osteoporosis.

Side-effects in men which directly result from its antiandrogenic action include gynecomastia (breast growth), galactorrhea (milk outflow), anderectile dysfunction.

Source:wikipedia