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Contraception Headings

Notes on Estrogen/Progestin Ratio, colour coding & COC availability in Australia.

Combined Oral Contraceptives [COC] Table

      [Table explanation (the science).               }

       Progestins used in Current COCs.                   For medical practitioners 

       Rationale for Androgen Assessment.        }

       References].                                                }

COC Characteristics

Matching COC Pill

Estrogen Sensitive Women

Progestagenic Pills

Estrogenic Pills

COC PBS Australia

COC Private Prescription Australia

Progestin Only Pill

Tailor Made Oral Contraceptive Pill

Using the Pill Continuously

Other Situations

The Estrogen/Progestin [E/P] ratio of COCs guides users as to the suitability of a pill for a particular woman. For estrogen sensitive women a low E/P ratio pill should be used. See tables below detailing pill suitability according to the E/P ratio & Womens' hormonal sensitivity.

The tables below are colour coded :- Blue for Progestins, Pink for Estrogens, Orange for Anti- Androgens. The deeper the colour the greater the effect.

PBS [Pharmaceutical Benefit Scheme Australia]

PP   [private prescription Australia]

Combined Oral Contraceptive [COC]- Table

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Progestins used in Current COCs

Progestin binding to the following receptors is variable and in some cases there is no binding at all : - progesterone, androgen, estrogen, glucocorticoid and mineralocorticoid receptors [PR, AR, ER, GR & MR] respectively.


Increased progestogenicity affects the endometrium by helping to control break through bleeding in an estrogen primed uterus. In some cases excessive progestogenic effects cause endometrial atrophy and thinning. In these cases estrogenization is required first. Uterine ultra sound [U/S] can assist in assessing this situation.


Increased androgenicity may help libido (debateable), but causes acne, hirsuteness, male type baldness and aggressive mood. Androgenicity also tends to raise LDL cholesterol and changes the lipid profile in a negative way. The following progestins attach to the androgen receptor [AR] causing androgenic effects  - levonorgestrel, norethisterone, desogestrel and gestodene. The following act as competitive agonists to androgens on the AR: - cyproterone acetate, drospirenone, nomegestrel and dienogest (diminishing effect respectively) and can assist in reversing these symptoms. Binding to Serum Hormone Binding Globulin [SHBG] is a crucial feature of a progstin’s influence on the degree of free serum androgen. Progestins such as levonorgestrel (48% bound) and norethisterone (36%) increase the level of free androgens, increasing these progestins’ androgenicity. [1 – 10, 28, 29]


Estrogens are associated with protecting the intima [inner most part of the lining] of the arteries and preventing bone loss but they stimulate the breast causing mastalgia [breast pain] and increase the thrombogenic [clotting] profile. Desogestrel and gestodene in conjunction with EE increase thrombotic risk two fold compared to EE with other progestins. Nomegestrel is cited as being beneficial. Progestins that are more likely to contribute to breast symptoms and hyperplasia are : - norethisterone, dienogest, desogestrel, gestogene and levonorgestrel. Progestins more protective of breast changes are :- cyproterone acetate, drospirenone and nomegestrol. [11 - 21] Progesterone is highly protective of the breast but is not incorporated into COCs.


Increased mineralocorticoid activity causes weight gain, hypertension and fluid retention. These symptoms are most likely to be secondary to estrogen, as progestins generally do not have significant fluid retention effects. Norethisterone or possibly levonorgestrel may minimally influence this. Drospirenone has antimineralocorticoid activity and reduces these symptoms. Gestodene has very mild antialdosterone effects i.e. opposes fluid retention. [22, 23, 29]

Rationale for Androgenicity Score

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 &


      [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.



1. Davis SR1, Bitzer JGiraldi APalacios SParke SSerrani MMellinger UNappi RE. Change to either a non androgenic or androgenic progestin-containing oral contraceptive      preparation is associated with improved sexual function in women with oral contraceptive-associated sexual dysfunction. J Sex Med. 2013 Dec;10(12):3069-79. doi: 10.1111/jsm.12310 Epub 2013 Sep 12.

2. Haspells, A. A. & Rolland, R. Benefits & Risks of Hormonal Contraception. MTP Press Ltd 1982

3. Kovacs, G T Pharmacology of progestogens used in oral contraceptives: An historical review to contemporary prescribing. Australian and New Zealand Journal of Obstetrics and Gynaecology, 43, Number 1, February 2003 , pp. 4-9(6)

4. Goodman and Gillman -  The Pharmacologic Basis of Therapeutics 2006 p 1566                                                              5. Arowojolu AO1, Gallo MFLopez LMGrimes DA. Combined oral contraceptive pills for treatment of acne. Cochrane Database Syst Rev. 2012 Jun 13;6:CD004425. doi:             10.1002/14651858.CD004425.pub5.                          6. Batukan C1, Muderris IIOzcelik BOzturk A. Comparison of two oral contraceptives containing either drospirenone or cyproterone acetate in the treatment of hirsutism. Gynecol Endocrinol. 2007 Jan;23(1):38-44.

7.  Muhn P, Fuhrmann U, Fritzemeier KH, Krattenmacher R, Schillinger E (1995). "Drospirenone: a novel progestogen with antimineralocorticoid and antiandrogenic activity".Ann. N. Y.

Acad. Sci. 761: 311–35. doi:10.1111/j.1749-6632.1995.tb31386.x.PMID 7625729.

8. Daniel Raudrant.  Progestogens with Antiandrogenic Properties. Drugs, March 2003, 63, Issue 5, pp 463-492 17 September 2012

9. Oettel M1, Carol WGräser TKlinger GMellinger UMoore CSchindler AEWinkler UH. Effect of ethinyl estradiol-dienogest combination on serum androgen concentrations.

Zentralbl Gynakol. 1997;119(12):597-606.

10. Merck Sharp and Dohme. Nomegestrol/oestradiol, Zoely. Aust Prescr 2011;34:194

11. Chez RA. Clinical aspects of three new progestogens: desogestrel, gestodene, and norgestimate. Am J Obstet Gynecol. 1989 May;160(5 Pt 2):1296–1300. [PubMed]

12. Christie T. A clinical overview of a new triphasic contraceptive containing gestodene. Int J Fertil.1989 Sep;34 (Suppl):40–49. [PubMed]

13. Rebar RW, Zeserson K. Characteristics of the new progestogens in combination oral contraceptives. Contraception. 1991 Jul;44(1):1–10. [PubMed]

14. Stefano Lello. Nomegestrol Acetate, Pharmacology, Safety Profile and Therapeutic Efficacy   Drugs, March 2010, 70, Issue 5, pp 541-559

15. Ruan X, Seeger H, Mueck AO. The pharmacology of nomegestrol acetate. Maturitas. 2012 Apr;71(4):345-53. Epub 2012 Feb 24.

16. Druckmann R. Progestins and their effects on the breast. Maturitas. 2003 Dec 10;46 Suppl 1:S59-69.

17. Campagnoli C, Abbà C, Ambroggio S, Lotano MR, Peris C. Differential effects of various progestogens on metabolic risk factors for breast cancer. Gynecol Endocrinol. 2007 Oct;23        Suppl 1:22-31.

18. Formby B, Wiley TS. Progesterone inhibits growth and induces apoptosis in breast cancer cells: inverse effects on Bcl-2 and p53. Ann Clin Lab Sci. 1998 Nov-Dec;28(6):360-9.                          19. André G. Actions of a 19-norprogesterone derivative on mammary gland: nomegestrol acetate. J Gynecol Obstet Biol Reprod (Paris). 2005 Feb;34(1 Pt 1):69-84.                                                  

20. Mueck AO, Sitruk-Ware R. Nomegestrol acetate, a novel progestogen for oral contraception. Steroids. 2011 Feb       21. Wiegratz I1, Lee JHKutschera EWinkler UHKuhl H. Effect of four oral contraceptives on hemostatic parameters. Contraception. 2004 Aug;70(2):97-106.                                                          

22. R W Kistner. Use of Progestins in Obstetrics & Gynaecology.  June 1970 pp 64, 75 & 92                                                   23. Epub 2010 Apr 6. Sehovic N, Smith KP. Risk of venous thromboembolism with drospirenone in combined oral contraceptive products. Ann Pharmacother. 2010 May;44(5):898-903.                

24. Elger W, Beier S, Pollow K, Garfield R, Shi SQ, Hillisch A (2003). "Conception and pharmacodynamic profile of drospirenone". Steroids. 68 (10-13): 891–      905.                                            

25. Schindler AE. Differential effects of progestins on hemostasis. Maturitas. 2003 Dec 10;46 Suppl 1:S31-7.                    26. Druckmann R. Progestins and their effects on the breast. Maturitas. 2003 Dec 10;46 Suppl 1:S59-69.                          27. Campagnoli C, Abbà C, Ambroggio S, Lotano MR, Peris C. Differential effects of various progestogens on metabolic risk factors for breast cancer. Gynecol Endocrinol. 2007 Oct;23           Suppl 1:22-31.                                           28. Nilsson B1, von Schoultz B. Binding of levonorgestrel, norethisterone and desogestrel to human sex hormone binding globulin and influence on free testosterone levels. Gynecol Obstet          Invest. 1989;27(3):151-4.                      29. A New M.Specific Progestogen for Low-Dose Oral Contraception. The Parthenon Publishing Group,1989. pp 11-29

Pill Characteristics

These women have the following characteristics : -

Long cycles >30 days

More excessive female sensitivity – Cry easily with sad or emotional   situations or sad TV shows

Nausea in early pregnancy

Nausea with estrogenic O/C


1.  Progestogenic pills -  Levlen [cheapest], Marvelon, Valette, Diane etc. Yaz, Yasmin or Femoden

2.  Reduce O/C dose Microgynon 20 etc.

3.  Progestin only O/C twice a day - Noriday, Micronor, Microlut, Microval

4.  “Tailor made pill”

     Reasons for Choice of Progestogenic Pills


         Patient Characteristics                                     Suggested Oral Contraception

         Break through Bleeding      [other causes excluded*]              Levlen [cheapest], Marvelon, Valette,

                            U/S – thick endometrium   > 10 mm.                            Diane etc. Yaz, Yasmin or Femoden

          Menorrhagia                                                                                             “ 

          Chloasma   [estrogenic effect].                                                         Low dose pills  - Loette, Levlen    

                                                                                                                               or progestin only pills :– 

                                                                                                                                Noriday, Micronor, Microlut, Microval

           Breast symptoms  [more likely an estrogenic effect]               More progestogenic COC, Marvelon,

                           or if Sx persist 3/12 after starting COC                               Valette, Diane etc., Yaz

                                                                                                                              or “Tailor made pill”. 

           * If bleeding persists it is important to exclude conditions such as poyps, endometrial infections or a                pre-cancerous uterine lining

Reasons for Choice of Estrogenic Pills


COC PBS Australia

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Taking the Pill Continuously


This is a good option for women who have painful periods.

Lower dose pills would be preferable. Over stimulation of the endometrium may cause breakthrough bleeding. If this happens occasionally, then cessation of the pill for a week would enable a period to occur. If breakthrough bleeding is more frequent perhaps every month or so then an alteration ­to a higher progestin dose may stop this bleeding. Alternatively it may indicate that this form of pill taking is unsuitable.


Most women who try this method have few problems if the appropriate pill is chosen following the guides listed above.


It should be considered that, if women are not wanting to conceive, there is no need to have periods. Having a period is only necessary if a fertile period fails to result in pregnancy. In such a situation the uterine lining is relatively thick and needs to be shed. However in women taking the pill the lining thins and does no need to be shed. Females in childhood, breast feeding or after menopause do not have periods. So it follows that women who do not wish to conceive when contracepting do not need to have periods.


Some women having menopausal hormone replacement may be prescribed cyclic therapy. This is not appropriate in view of the rationale described above and just detracts from one of the advantages of menopause, not having to deal with monthly bleeding!

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