Evidence-based Resources in Current and Alternative Therapies
Compiled by: Constantine Kaniklidis, medical researcher

Home Menopause [updated: 06/19/04]

  Menopause/HRT: Findings

Menopause: Treatment


News: Menopause

  • NAMS Position Statement on Hot Flashes: (added: 03/15/04)
    NAMS (The North American Menopause Society) has issued a position statement on The Treatment of Menopause-associated Vasomotor Symptoms (published in their journal Menopause).

  • Tibolone: (updated: 06/19/04)
    New study
    (click to read), reported in the journal Contemporary Ob/Gyn and cross-reported on
    Medscape, has demonstrated the viablility of tibolone ((derived from soybeans and yams, and already well-established for its ability to prevent bone loss) as an alternative to HRT, and this landmark report furthermore found tibolone as effective as HRT in the relief of hot flashes and vaginal dryness, while significantly improving sexual repsonse, all with an excellent side effect profile.

    Tibolone (Organon) is a tissue-specific synthetic steroid (a norethisterone derivative from soybeans and yams) currently used in Europe (as Livial) for osteoporosis prevention and treatment. Technically, it is now classified as a STEAR (selective tissue estrogenic activity regulator) and it is thought to potentially exhibit estrogenic, androgenic, and progestogenic activities. However, Kutlu et al. (Maturitas:
    Mammographic Breast Density Changes After 1 year of Tibolone Use) found that tibolone does not evince an estrogenic effect on breast cells and concluded that "it might limit, even reverse breast density increase, especially in postmenopausal women with high breast density". In this connection, Valdivia et al (Fertil Steril: Effects Of Tibolone and Continuous Combined Hormone Therapy On Mammographic Breast Density and Breast Histochemical Markers in Postmenopausal Women) found that tibolone treatment for one year induced decreased breast density in contrast to CEE-MPA (continuous conjugated equine estrogens combined with medroxyprogesterone acetate) which induced increased breast density. In adition, results of animal studies demonstrate that tibolone can shrink breast cancer tumors at a level of efficacy matching that of tamoxifen.

    It has also been shown to be at least as effective as HRT in both the prevention of bone loss and the relief of menopausal symptoms, even out to 8 years (see Prelevic at al. (Maturitas:
    The Effect of Tibolone on Bone Mineral Density in Postmenopausal Women with Osteopenia or Osteoporosis -- 8 Years Follow-Up) and thus is a viable and safe HRT alternative (on menopausal symptom relief; see also Riera-Espinoza et al. (Maturitas: Changes in bone turnover during tibolone treatment). Also consult the Evidencewatch coverage on Menopause).

    The LIFT (Long-term Interventional Fracture Study in Osteoporotic Patients) trial (in the Nettherlands), as well as trials at USCD and Rush-Presbyterian-St. Luke’s Medical Center (Chicago,) among others, are assessing tibolone's effect on fracture risk reduction.

    In sum, tibolone exhibits several additional beneficial activities. It lowers estrogen breast tissue concentration, with no cell-proliferative activity, potentially protective in breast cancer (the ongoing LIBERATE trial will clarify this further). In terms of cardiovascular impact, it appears to slightly lower HDL (although this returns to baseline after 3 years) but does not increase LDL; however this is balanced by other beneficial actions: (1) it lowers total cholesterol, (2) reduces lp(a) (lipoprotein(a)), (3) exhibits angina-protective activity through its anti-ischemic effect, among other positive cardiovascular effects. The cumulative cardiovascular impact in this context appears to be neutral so that tibolone would not significantly increase CAD (coronary artery disease) risk, a finding to be further clarified in the ongoing OPAL trial. (See also the recent appreciation of tibolone in Menopause: New Therapies, published in MJA). Evidencewatch will continue to report on in-progess tibolone trials (LIFT, OPAL, LIBERATE and THEBES) as the findings become available to us.

    Tibolone and Carotid Atherosclerotic Lesions :
    One intriguing recent finding is that tibolone may, in addition to its benefits for menopausal symptoms and bone health, counteract carotid atherosclerotic lesions as well as induce reductions in Lpa (lipoprotein(a)), total-cholesterol, and LDL-C (LDL-cholesterol) in postmenopausal women; see Anedda et al. (Hormone Research: Observational Study on the Efficacy of Tibolone in Counteracting Early Carotid Atherosclerotic Lesions in Postmenopausal Women).

    Evidencewatch Commentary:
    In a recent comprehensive review of tibolone in Contemporary OB/GYN, the authors examine the issue of endometrial effects and conclude: "We can state with confidence that tibolone does not cause endometrial proliferation" although the authors acknowledge that isolated cases of endometrial proliferation have been reported. However, one just released study ( Perez-Medina et al.:
    Tibolone and Risk of Endometrial Polyps: A Prospective, Comparative Study with Hormone Therapy) in NAMS Menopause, has found that tibolone significantly increased the risk of endometrial polyps. The import of this seemingly contrary finding is not clear at present, and Evidencewatch speculates that it may have been dose-dependent, as the study use 2.5mg/daily of tibolone (typical for menopausal symptom relief), although 1.25mg/daily is an alternate deployable regimen known to still have favorable anti-osteoporotic benefit. We await the results of further studies and trials to clarify this issue, especialy the forthcoming results of the THEBES (Tibolone Histology of the Endometrium and Breast Endpoints Study) trial.

    Clarification of FDA status: Marketed as Livial®, from Organon, tibolone is already approved in over 70 countries, for the treatment of climacteric symptoms (also approved in some countries for osteoporosis prevention and treatment). In the U.S., tibolone is currently at the clinical trials stage.

  • Black Cohosh:
    Recently reported in Menopause (click to read abstract), the Journal of the North American Menopause Society (NAMS) is a critical study that ". . . clearly supports the safety of specific Cimicifuga extracts [Black Cohosh], particularly isopropanolic preparations, for use in women experiencing menopausal symptoms and as a safe alternative for women in whom estrogen therapy is contraindicated". Evidencewatch will continue to update this and other rleveant findings as they appear.

  • ALERT: New study (click for summary), the British Million Women Study, reported in Lancet (Aug. 9, 2003), indicates increased risk of breast cancer for women using combined estrogen + progestagen HRT. See also the Medscape commentary, and the NAMS commentary. Evidencewatch now provides a number of commentaries on this latest finding (see under Menopause/HRT: Findings).


Copyright © 2004. Constantine Kaniklidis