Progesterone and all progestogens increase MAO activity which can affect libido Re: The pill and women’s sexuality
Richard Quinton’s response advises women with reduced libido on a COC to switch to one containing norethisterone acetate (NEA). He believes that NEA is not only of low thrombogenicity, but is also the most androgenic of progestogens and may have a favourable effect on libido in some women.1 Is this correct?
Richard Dickey’s book “Managing contraceptive pill patients” lists the androgenic activity for levonorgestrel as 8.3 but only 1.0 for norethindrone (norethisterone) 1.6 for norethindrone acetate.2 These results were obtained from a rat ventral prostate assay in which testosterone was 50.
Also, norethisterone has the same increased risk of thrombosis as levonorgestrel.
Any current use of combined OCs has a 3-fold increased risk of idiopathic venous thromboembolism compared with no use in the past year. Risks doubled for newer progestogens with desogestrel (x4.28), gestodene (x4.27), drospirenone (4.12) and cyproterone (4.27) compared with levonorgestrel (2.38), norethisterone (2.56) and norgestimate (2.53).3
It is important to realise that all effective hormonal contraceptives must be predominantly progestogenic to avoid pregnancy. Progesterone and progestogens increase the monoamine oxidase levels which is a major cause of depressive mood changes and loss of libido. In the London 1960s oral contraceptive trial the first-year incidence of depressive mood changes including loss of libido ranged from 10% to 30% with norethisterone acetate combinations containing higher doses of oestrogen than are used now. The enzyme monoamine oxidase inactivates, or stores, monoamines which control mood and behaviour and vascular reactivity and similar increases are found in the blood and brain.4,5
Some women did complain of increased libido and even violence; “ My husband was exhausted”, or, “ I wanted to sexually assault the bus driver”, or, “ I threw a frozen chicken at my husband”. One COC in particular had these effects and also induced most endometrial blood (arteriolar and sinusoid) vessel changes. These effects are similar to effects of the premenstrual syndrome - a time when MAO also increases and severe mental disturbances are more likely.
1 Quinton R. https://www.bmj.com/content/364/bmj.l335/rapid-responses
2 Dickey RP. Managing contraceptive pill patients. Eighth Edition 1977 EMS pp130-131.
3 Vinogradova Y, Coupland C, Hippisley-Cox J. Use of combined oral contraceptives and risk of venous thromboembolism: nested case-control studies using the QResearch and CPRD databases .Brit Med J 2015;350:h2135
4 Grant ECG, Pryse Davies J. Effect of oral contraceptives on depressive mood changes and on endometrial monoamine oxidase and phosphatases. Brit Med J 1968;3:777-780.
5 Southgate J, Grant ECG, Pollard W, Pryse Davies J, Sandler M. Cyclical variations in endometrial monoamine oxidase: Correlations of histochemical and quantitative bio chemical assays. Biochemical Pharmacology 1968; 17:21-26.
Competing interests: No competing interests