Combined Oral Contraceptive [COC]- Table

Rationale for Androgenicity Score

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These are arbitrary numbers based on assessments described in the literature of androgenicity from animal and clinical studies. The notes below explain how these scores have been developed. It is to be used as a guide to the relative androgenic effects of the formulations listed. Some studies give numbers for the relative androgenic effects of some of the “pills” but there are significant disparities in some of these figures when other studies and the hormonal pharmacodynamics are considered.

 

 ß   Desogestrel [2, 3, 25, 26, 27] Competitive agonist on the Androgen Receptor [AR] with higher receptor affinity

        than levonorgestrel. It inhibits ovulation at a lower dose than levonorgestrel but the formulation  

      [Femoden] contains four times the LN equivalent to Levlen and has a low E/P ratio making Marvelon

      theoretically much more androgenic.

      Desogestrel [Marvelon] has similar androgenicity to gestodene [Femoden & Minulet] but as Marvelon’s E/P ratio

     is much lower it is more androgenic giving this formulation a higher androgen score.

     Desogestrel does not bind to SHBG and therefore does not displace testosterone from this globulin unlike

     levonorgestrel and norethisterone. This helps counteract its androgenic tendencies.

 

 †  Dienogest [1]  Ovulation inhibition is by direct action on the ovary & not centrally on the hypothalamus &

      pituitary.

      [Valette]  With EE the serum hormone binding globulin (SHBG) is raised and is the mechanism for reducing free

      testosterone and reducing these formulations’ androgenicity.

      [Qlaira]  The relative androgenicity of COCs containing dienogest depend on the dosage of estrogen in the

      particular formulation making Qlaira less androgenic. Pharmacologically it has no androgenic effects.

 

 ††  Cyproterone Acetate (CPA) [5]         

      [Brenda] Is a potent competitive agonist of the Androgen Receptor (AR) and selectively blocks both testosterone        (T) and dihydrotestosterone (DHT).

      It stimulates SHBG and is potent in suppressing progesterone, estrogen, T, DHT, LH & FSH. It therefore has a              triple mechanism in reducing the effects of androgens. It reduces the production of androgens from the                      adrenals and ovaries; competes with their attachment to the AR; and decreases circulating free androgens by            increasing serum androgen binding to SHBG.

 

 ¥   Drospirenone [6, 7, 24A] less potent competitive agonist than CPA but also has direct action on the AR.

            [Yaz]                   In clinical studies drospirenone has an equal effect on hirsutness to CPA.

            [Yasmine]          It is less effective than CPA in treating acne.

            [Isabelle]           The relative androgenicity of COC containing drospirenone depends on the dosage of                                                       estrogen in the particular formulation.

 

 ¶   Nomegestrol acetate [10, 14, 15] Does not attach to the AR so is not a competitive androgenic agonist.

            [Zoley]              In high doses acts centrally on the progesterone receptor (PR) and thereby may suppress T                                               production from the ovary and adrenal.

            It is less effective than CPA & drospirenone but more so than desogestrel and levonorgestrel in treating acne.

            Estriol has a substantially shorter half life than EE and may affect Zoley’s ability to raise SHBG levels and the                resultant lowering of free T. [10, 14, 15]

 

 Ω        Gestodene [3, 26, 29] It is a competitive agonist on the AR with higher receptor affinity than levonorgestrel                 and is less masculinizing than levonorgestrel in laboratory animals.

             Gestodene inhibits ovulation at a lower dose than levonorgestrel but the formulation Femoden contains                     double the LN  equivalent to Levlen and has a lower E/P ratio.                                   

             [Minulet] This makes Feoden/Minulet theoretically more androgenic.

             Gestodene has a low binding affinity to the SHBG, which reduces its androgenicity.

             It has a similar androgenicity to desogestrel but Femoden and Minulet have a higher E/P ratio which                             explains the lower androgen score on this chart verses Marvelon.

                                                           

 l          Levonorgestrel [2, 8, 29] Competitive agonist on the AR with 7% of the activity of testosterone.

            [Microgynon etc.] Lowers SHBG within the first month and by six months is down to 41%. This increases the                 availability of free androgens.

            Levonorgestrel combinations with higher E/P ratios will have lower androgenicity.

            [Logynon etc.]    

                                   

 ñ        Norethisterone [28, 29] Competitive agonist on the AR with about 1.6% of the activity of testosterone.

            [Brevinors etc.]   Lowers SHBG in dose dependant manner so that higher norethisterone doses have higher                androgenicity.

            [Norinyl-1]] Because norethisterone needs 10x the dose of levonorgestrel to inhibit ovulation they have                       similar androgenic profiles in COC agents.