Three cases of endometrial cancer associated with "bioidentical" hormone replacement therapy.
ABSTRACT We describe three women who developed endometrial cancer after taking "bioidentical" hormone replacement therapy (HRT) to relieve menopausal symptoms. Although pharmaceutical HRT is a well established and tested therapy, little is known about the quality control, safety and efficacy of bioidentical HRT. Women should be advised to avoid bioidentical HRT, and those who continue to use it should receive regular endometrial surveillance.
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ABSTRACT: Menopausal symptoms affect a significant portion of women. Traditional treatment with manufactured hormone therapy can alleviate these symptoms, but many women and their health care providers are concerned about the risks, such as venous thromboembolism and certain types of cancer, demonstrated with manufactured hormone therapy. Compounded bioidentical hormone therapy has been proposed and is often used as a solution for these concerns. Despite this use, no data are currently available to support the claims that compounded bioidentical hormone therapy is a safer or more efficacious option compared with manufactured hormone therapy. A common misperception is that all manufactured products consist of synthetic hormones and all compounded medications consist of natural hormones; however, in fact, significant overlap exists. Several key stakeholder organizations have issued statements expressing concern about the lack of evidence regarding the efficacy and safety of compounded bioidentical hormone therapy, in addition to concerns regarding prescribing patterns. The Women's Health Practice and Research Network of the American College of Clinical Pharmacy recommends against the consistent use of compounded bioidentical hormones as a safer option compared with manufactured therapy and supports the statements of other key organizations, acknowledging the need for more robust clinical studies to evaluate the potential advantages and disadvantages of compounded bioidentical products compared with manufactured products.Pharmacotherapy 01/2014; · 2.31 Impact Factor
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ABSTRACT: Abstract After the publication of the Women's Health Initiative, attitudes towards management of menopausal symptoms changed dramatically. One alternative that has received much media attention is the use of bioidentical hormone therapy (BHT). The media and celebrity endorsements have promoted a number of misconceptions about the risks and benefits associated with the various forms of BHT. This article will review the available evidence regarding the safety and efficacy of BHT in comparison to conventional hormone therapy. We will also review several cases seen in our midlife women's referral clinics, which demonstrate concerns for the safety and efficacy of BHT, including unexplained endometrial cancer in otherwise healthy BHT users. Due to the lack of sufficient data to support the efficacy or safety of BHT, we recommend the use of United States Food and Drug Administration-approved regimens in the management of menopausal symptoms.Journal of Women's Health 08/2014; 23(8):642-648. · 1.90 Impact Factor
- The Journal of Clinical Endocrinology and Metabolism 12/2011; 97(3):756-9. · 6.31 Impact Factor
244MJA • Volume 187 Number 4 • 20 August 2007
The Medical Journal of Australia ISSN: 0025-
729X 20 August 2007 187 4 244-245
©The Medical Journal of Australia 2007
diagnostic hysteroscopy and curettage. The tissue diagnosis was
Between June 1998 and July 2002, she used “bioidentical” HRT
as troches. Each troche contained: oestradiol, 1.75mg; progester-
one, 300mg; testosterone, 4.5mg; and dehydroepiandrosterone
(DHEA), 5mg. The initial dose was half a troche per day, dissolved
in the mouth.
Between July 2002 and December 2004, she used one-eighth of
a troche in the morning and one-quarter in the evening. Each
troche contained: trieste (oestrone, oestradiol, oestriol), 3.0mg;
progesterone, 400mg; testosterone, 1.5mg; and DHEA, 5mg.
Early in 2004, she presented with several episodes of vaginal
bleeding, and an ultrasonic scan revealed a thickened endometrial
lining (combined thickness, 18mm; normal for a postmenopausal
woman is <5mm). Hysteroscopy confirmed a grossly abnormal
endometrium with abnormal vascularisation. Curettage revealed a
grade 2 endometrioid carcinoma. She underwent total abdominal
hysterectomy and bilateral salpingo-oophorectomy. The final diag-
nosis was stage IA, grade 2 endometrial cancer.
A 71-year-old non-diabetic woman had been on some form of
hormone replacement therapy (HRT) since the age of 49 years. She
took oral oestrone sulfate 1.25mg daily and medroxyprogesterone
acetate 10mg for at least 10 days a month for 8 years. For the next
2 years, she used a 3.2% compounded topical progesterone cream
(at a daily dose of “one level spoonful”). In December 1997, she
had some irregular vaginal bleeding, which was investigated by
A 59-year-old non-diabetic woman, who had been menopausal
from age 51 years, used “bioidentical” HRT as troches containing
oestradiol, progesterone, testosterone and DHEA (doses unknown)
from November 2001. From May 2003, she had noted continuous
vaginal bleeding. An ultrasonic scan showed that the endometrial
thickness was 19mm. Diagnostic curettage in July 2003 confirmed
a diagnosis of complex endometrial hyperplasia with atypia. She
was referred to the Gynaecological Cancer Centre at the Royal
Hospital for Women in September 2003, and underwent total
abdominal hysterectomy and bilateral salpingo-oophorectomy.
The final diagnosis was stage IB, grade 2 endometrial cancer.
A 54-year-old non-diabetic woman presented with irregular vagi-
nal bleeding. She had been using troches made by a compounding
chemist for several years (precise time unknown). This treatment
had been commenced while she was still menstruating. The
troches had contained varying doses of DHEA, oestrone, oestra-
diol, oestriol and progesterone (doses unknown). The troches were
posted to her by mail and she was monitored by telephone
conversations with a nurse.
A pelvic ultrasound revealed a thickened endometrium; hyster-
oscopy and curettage showed a polypoid lesion at the fundus.
Histopathology revealed grade 2 endometrial cancer. She under-
went total abdominal hysterectomy and bilateral salpingo-
oophorectomy, and the final diagnosis was stage IA, grade 2
Pharmaceutical HRT is a well established and tested therapy for the
relief of menopausal symptoms such as hot flushes.1 The risks,
benefits and adverse effects of pharmaceutical HRT have been
established in large randomised controlled trials such as the
Women’s Health Initiative study.2 For example, unopposed oestro-
gen is known to be associated with an increased risk of endome-
trial carcinoma,3 so a progestin is added to prevent this
complication. Pharmaceutical progestins, when used appropri-
ately, are very effective in preventing endometrial carcinoma.3
Pharmaceutical medications undergo rigorous quality control,
safety and efficacy testing. In Australia, pharmaceutical medicines
are regulated by the Therapeutic Goods Administration.
In contrast to this, compounding chemists can “hand make”
pharmaceuticals in novel delivery systems. Currently, these com-
pounds are not directly regulated by the Therapeutic Goods
Administration. Thus, little is known about the quality control,
pharmacokinetics, safety and efficacy of these treatments. Com-
pounded hormone replacement therapy is often termed “bioidenti-
cal” HRT. Typically, bioidentical HRT contains three oestrogens
(oestrone, oestradiol and oestriol), progesterone, and androgens
such as testosterone and DHEA, and is usually given either as
cream rubbed onto the skin or as troches. Often, bioidentical HRT
is monitored using blood or salivary levels of sex hormones. If the
dose of progesterone is insufficient to prevent oestrogen-induced
endometrial hyperplasia, then these treatments might cause
When testing new HRT regimens, endometrial assessment is one
of the most important safety endpoints. The usual method used for
evaluating the endometrium in HRT trials is endometrial biopsy
(usually performed every 6–12 months). In its guidelines to the
pharmaceutical industry, the United States Food and Drug Admin-
istration recommends endometrial biopsies at the beginning and
Three cases of endometrial cancer associated with
“bioidentical” hormone replacement therapy
John A Eden, Neville F Hacker and Michael Fortune
We describe three women who developed endometrial cancer after taking “bioidentical” hormone
replacement therapy (HRT) to relieve menopausal symptoms. Although pharmaceutical HRT is a well
established and tested therapy, little is known about the quality control, safety and efficacy of bioidentical
HRT. Women should be advised to avoid bioidentical HRT, and those who continue to use
it should receive regular endometrial surveillance. (MJA 2007; 187: 244-245)
end of an HRT trial.4 Sometimes ultrasound can give additional
useful information (endometrial thickness, polyps, fibroids etc).
The current “gold standard” test for endometrial assessment is
hysteroscopy and curettage.
The three cases reported here raise the possibility that the
oestrogen component of the troche was significantly absorbed but
the dose of progesterone was inadequate, thereby causing endome-
trial hyperplasia. The North American Menopause Society has
produced a useful discussion paper on bioidentical HRT,5 and it
should be noted that the Australasian Menopause Society does not
recommend the use of bioidentical HRT.6,7 Until this therapy has
been properly tested, it may be prudent not to advocate bioidenti-
cal HRT and to perform endometrial surveillance (eg, annual
transvaginal ultrasound and endometrial biopsies) on women
who, despite counselling, continue to use bioidentical HRT.
John Eden is a consultant for Wyeth, AstraZeneca, Arkopharma, and Lawley
John A Eden, FRANZCOG, FRCOG, CREI, Associate Professor of
Reproductive Endocrinology, School of Women’s and Children’s
Neville F Hacker, FACOG, FACS, CGO, Professor of Gynaecological
Oncology,1,2 and Director, Gynaecological Cancer Centre2
Michael Fortune, MBBChir, FRCOG, FRANZCOG, Visiting Medical
1 University of New South Wales, Sydney, NSW.
2 Royal Hospital for Women, Sydney, NSW.
3 Prince of Wales Private Hospital, Sydney, NSW.
1 MacLennan A, Lester S, Moore V. Oral estrogen replacement therapy
versus placebo for hot flushes: a systematic review. Climacteric 2004; 4:
2 Writing Group for the Women’s Health Initiative Investigators. Risks and
benefits of estrogen plus progestin in healthy postmenopausal women:
principal results from the Women’s Health Initiative randomized control-
led trial. JAMA 2002; 288: 321-333.
3 Gambacciani M, Monteleone P, Sacco A, Genazzani AR. Hormone
replacement therapy and endometrial, ovarian and colorectal cancer.
Best Pract Res Clin Endocrinol Metab 2003; 17: 139-147.
4 Center for Drug Evaluation and Research. Guidance for industry. Estro-
gen and estrogen/progestin drug products to treat vasomotor symptoms
and vulvar and vaginal atrophy symptoms — recommendations for
clinical evaluation [draft guidance]. Rockville, MD: CDER, 2003. http://
www.fda.gov/cder/guidance/5412dft.pdf (accessed Jul 2007).
5 North American Menopause Society. Understanding the controversy:
hormone testing and bioidentical hormones. Proceedings of the Post-
graduate Course prior to the 17th Annual Meeting of the North American
Menopause Society. Nashville, Tennessee; 2006; 11 Oct. http://
www.menopause.org/edumaterials/PG06monogrpah.pdf (accessed Jul
6 Australasian Menopause Society. Bioidentical hormones (troches) advice
to consumers [media release]. 29 Nov 2003. http://www.meno-
pause.org.au/public/media_detail.asp?ID=38 (accessed Jul 2007).
7 Australasian Menopause Society. Bioidentical hormones (troches) advice
for doctors [media release]. 29 Nov 2003. http://www.menopause.org.au/
public/media_detail.asp?ID=39 (accessed Jul 2007).
(Received 23 May 2007, accepted 27 Jun 2007)