Maternal Death
Vol. 15 No 1 | Autumn 2013
Tibolone and libido

This article is 11 years old and may no longer reflect current clinical practice.

I would like to express concerns regarding the content of the article ‘Tibolone and libido: it’s not a trivial pursuit’ O&G Magazine Vol 14 No 4 Summer 2012. My concerns pertain to comments that have been made about hormone replacement therapy (HRT) in general, tibolone and testosterone therapy.

That ‘HRT may have the effect of improvement in cognitive information processing’ is a highly controversial and potentially misleading statement. As summarised by Maki in her recent review, the effects of HRT vary with the mode of administration and formulation of oestrogen used with the use of progestin and type of progestin being also a major determinant of any positive or negative cognitive effect.1

Observational data suggest micronised progesterone may be less harmful in terms of breast cancer risk than other progestins2, although this remains uncertain. In contrast, there is uncertainty as to whether the Mirena intrauterine device is or is not associated with breast cancer risk when used as HRT, with one large observational study indicating that it does carry a risk.3 Therefore, the information given in paragraph three of the article is not accurate.

The effects of tibolone on mood are not significantly greater than those seen with conventional oestrogen therapy. One RCT comparing tibolone to transdermal oestradiol plus norethisterone in women with female sexual dysfunction (FSD) showed comparable effects of the two therapies. Based on this and other studies, it is completely incorrect to suggest preferred use of tibolone over other regiments for its effects on mood, libido or menopausal symptoms.4 There is no research that supports the suggestion that tibolone is more effective for mood and libido in postmenopausal women without FSD.

On the second page of the article, the author states: ‘Tibolone with HRT and daily oral DHEA provided significant improvement in sexual function…’ This statement indicates a lack of understanding of the published literature. Firstly, it suggests tibolone can be combined with HRT, which is incorrect. Secondly, the study that has been referenced for DHEA reported a within group improvement in sexual function with DHEA therapy from baseline, but no greater efficacy when compared with placebo (between group comparison) and the study numbers were small.5 It was a negative study. Consistent with this, no robust RCT has demonstrated a benefit of DHEA on libido in postmenopausal women.6

The table listing contraindications to tibolone is incorrect. Being over 60 years of age is not a contraindication to the prescription of tibolone. Several studies have been conducted in women aged 60 to 79 years. In this age group a 1.25mg dose of tibolone is more effective than raloxifene for prevention of bone loss.7 In addition, 1.25mg of tibolone daily is associated with a significantly lower rate of breast cancer, a significantly low rate of colon cancer, a significant reduction in fractures, no increased risk of thrombosis and no increase in cardiac events.8 There was a small but significant increase risk of ischaemic stroke, but the absolute number was so small that in terms of prevention of fracture, tibolone lines up extremely well against other therapeutic options in this population. I commonly recommend women age 60+ take 1.25mg (a half tablet) daily.

No study has ever demonstrated an increase in venous thrombo-embolic events with tibolone. Therefore, a past history of VTE is not an absolute contraindication and, in fact, tibolone is usually the safest option for symptomatic women with this medical history.

With respect to the use of AndroFeme one per cent, it is wrong to recommend ‘transdermal testosterone therapy should only be used when testosterone levels are measured and low levels identified’. This has not been an inclusion criterion for any of the large RCTs that have shown significant benefit with testosterone therapy in postmenopausal women for low libido, for example APHRODITE9, ADORE.10 Considering how inaccurate testosterone measurements are in women, this statement has the potential to prevent women who would benefit from therapy from being treated.

Measurement of testosterone should not include measurement of ‘free testosterone’ as the available assays to measure free testosterone lack the precision to enable them to be of clinical use. It is acceptable for a laboratory to calculate free testosterone from a recognised equation such as Sodergard11 if testosterone has been measured with precision. The free androgen index is not a useful guide for testosterone therapy and women and should really only be applied to assessment of conditions of androgen excess such as polycystic ovarian syndrome.

That ‘androgen value should be in the lowest quartile of normal ranges from reproductive-age women’ in order for someone to be treated, contradicts the existing evidence and is not an appropriate clinical recommendation.12 It was a suggestion made a decade ago based a consensus of opinion (including my own)13 that has been refuted by published data.

Transdermal testosterone cream should not be applied to the arm for two reasons: first, application to the arm commonly interferes with subsequent measurement of testosterone levels for safety monitoring, inappropriately high levels from either a reservoir in the skin of the arm or contamination of the blood draw are common; and, second, the venous drainage from the arm involves breast vasculature and there is no knowledge as to the resultant effects. Transdermal testosterone therapy should only be applied to the lower torso or upper outer thigh (not the inner thigh).

The final conclusion that tibolone should be avoided in women over the age of 60 will deny women what should be considered optimal therapy for this age group – it is probably the safest therapeutic option for women 60+ who continue to experience menopausal symptoms or who have osteopenia or osteoporosis without fracture.


  1. Maki PM. Minireview: effects of different HT formulations on cognition. Endocrinology. 2012;153(8):3564-70.
  2. Fournier A, Fabre A, Mesrine S et al. Use of different postmenopausal hormone therapies and risk of histology- and hormone receptor-defined invasive breast cancer. J Clin Oncol. 2008;26(8):1260-8.
  3. Lyytinen HK, Dyba T, Ylikorkala O, Pukkala EI. A case-control
    study on hormone therapy as a risk factor for breast cancer in Finland: Intrauterine system carries a risk as well. Int J Cancer. 2010;126(2):483-9.
  4. Nijland EA, Weijmar Schultz WC, Nathorst-Boos J et al. Tibolone and transdermal E2/NETA for the treatment of female sexual dysfunction in naturally menopausal women: results of a randomized active-controlled trial. J Sex Med. 2008;5(3):646-56.
  5. Genazzani AR, Stomati M, Valentino V et al. Effect of 1-year, low-dose DHEA therapy on climacteric symptoms and female sexuality. Climacteric. 2011;14(6):661-8.
  6. Davis SR, Panjari M, Stanczyk FZ. DHEA Replacement for Postmenopausal Women. J Clin Endocrinol Metab. 2011;96(6):1642-53.
  7. Delmas PD, Davis SR, Hensen J et al. Effects of tibolone and raloxifene on bone mineral density in osteopenic postmenopausal women. Osteoporos Int. 2008;19(8):1153-60.
  8. Cummings SR, Ettinger B, Delmas PD et al. The effects of tibolone in older postmenopausal women. N Engl J Med. 2008;359(7):697-708.
  9. Davis SR, Moreau M, Kroll R et al. Testosterone for Low Libido in Menopausal Women Not Taking Estrogen Therapy. N Eng J Med. 2008;359:2005-17.
  10. Panay N, Al-Azzawi F, Bouchard C et al. Testosterone treatment of HSDD in naturally menopausal women: the ADORE study. Climacteric. 2010;13(2):121-31.
  11. Sodergard R, Backstrom T, Shanhag V, Carstensen H. Calculation of free and bound fractions of testosterone and estradiol-17 beta to human plasma proteins at body temperature. Journal of Steroid Biochemistry and Molecular Biology. 1982;16(6):801-10.
  12. Davis SR, Davison SL, Donath S, Bell RJ. Circulating androgen levels and self-reported sexual function in women. JAMA. 2005;294(1):91-6.
  13. Bachmann GA, Bancroft J, Braunstein G, et al. Female androgen insufficiency: The Princeton Consensus Statement on definition, classification and assessment. Fertil Steril. 2002;77(660):665. RCOG

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