I get to be wrong… I just wonder why so much is said about reducing circulating E2 levels related to women being treated for breast cancer. That is why I was concerned about E2 levels. I’m not a doctor, and you are.
Please explain how aromitase inhibition is not useful in surgically intact premenopausal women as I am confused. Everything I have read states fibroid tumors are the result of a woman being estrogen dominant, and using estrogen “blockers” will help to shrink them.
Unless we are discussing two different issues; why did the woman in question find almost complete relief of her (monthly) fibroid related pain by using and AI to (hopefully)reduce the size of her fibroids?
Thanks in advance, doc.
KNB[/quote]YOu are too kind. We all get to be wrong, I more often than most. Since you ask, the answer to the question of AI in pre-menopausal women is…“It depends.” It depends on age and circumstance whether circulating estrogen is effected. You may recall that I am skeptical that circulating estrogen reflects all the effects of an AI on health. SO here, as proof, I answer your second question on fibroids (short version at the end):
1: Reprod Biomed Online. 2008 Oct;17(4):569-74.
Treatment of symptomatic uterine leiomyoma with letrozole.
… Ovarian hormones seem to
play an essential role in pathogenesis, and deprivation of ovarian oestrogen
causes leiomyomas to shrink significantly. The purpose of this study was to
evaluate the effects of the non-steroidal aromatase inhibitor letrozole on
uterine leiomyomas and on bone metabolism. A prospective, open clinical trial was
conducted in a university-based hospital. Sixteen premenopausal women with
symptomatic uterine leiomyomas were treated with letrozole 5 mg/day orally for 3
months. The main outcome measures of uterine and uterine leiomyoma sizes, serum
FSH, LH, oestradiol concentrations, ovarian volumes and myoma-related symptoms
were noted at baselines and once a month during treatment. Lumbar spine bone
mineral density and biochemical markers of bone metabolism were studied at the
beginning and at the end of 3 months. Letrozole significantly decreased uterine
leiomyoma sizes (P < 0.01) and promptly benefited women with heavy menstrual
bleeding associated with leiomyomas without changing bone mineral density.
Aromatase inhibitors may represent a new generation of medications for the
treatment of leiomyoma and associated symptoms. Larger clinical trials are
needed, however, to fully evaluate their safety and efficacy.
5: Best Pract Res Clin Obstet Gynaecol. 2008 Aug;22(4):655-76. Epub 2008 May 12.
Medical management of fibroids.
Sankaran S, Manyonda IT.
St George’s Hospital NHS Trust, Department of Obstetrics and Gynaecology,
Blackshaw Road, London SW17 0QT, UK.
The ideal medical therapy for fibroids is, arguably, a tablet that is taken by
mouth, once a day or, even better, once a week, with minimal, if any,
side-effects, that induces fibroid regression and thus a resolution of symptoms
rapidly, but without affecting fertility. Such a magic bullet does not yet exist,
and there are no indications that one is on the horizon. Driven by the
observation that fibroid growth is hormone dependent, current medical treatments
mainly involve hormonal manipulations. Gonadotrophin-releasing hormone analogues
(GnRHa) have been the most widely used, and while they do cause fibroid
regression, they can only be used in the short term, as temporizing measures in
the perimenopausal woman, or pre-operatively to reduce fibroid size, influence
the type of surgery, restore haemoglobin levels and apparently reduce blood loss
at operation. They are notorious for rebound growth of the fibroids upon
cessation of therapy, and have major side-effects. …
Aromatase inhibitors only appear to be effective in postmenopausal women, have
potentially significant long-term side-effects, and experience with their use is
7: Fertil Steril. 2009 Jan;91(1):240-3. Epub 2008 Feb 4.
Action of aromatase inhibitor for treatment of uterine leiomyoma in
Hilário SG, Bozzini N, Borsari R, Baracat EC.
Department of Obstetrics and Gynecology, University of São Paulo Medical School,
São Paulo, Brazil. email@example.com
OBJECTIVE: To assess the effect of the aromatase inhibitor on patients with
leiomyoma in the reproductive stage regarding reduction of uterine volume and
control of symptoms. DESIGN: Clinical study. SETTING: Academic clinical practice.
PATIENT(S): Twenty patients, over 35 years of age, with symptomatic uterine
leiomyoma. INTERVENTION(S): Anastrozol, 1 mg/day for 12 weeks. MAIN OUTCOME
MEASURE(S): Measurement of uterine volume, assessment of symptoms related to
uterine leiomyoma, serum assay of follicle stimulating hormone (FSH), and
estradiol. RESULTS: Average reduction of uterine volume of 9.32%, attaining up to
32%, and reduction of symptoms of uterine leiomyoma (menstrual volume, duration
of menstruation, and dysmenorrhea). No significant change in serum levels of FSH
and estradiol during use of the medication were observed. CONCLUSION(S):
Anastrozol proved to be effective in reducing the volume of the uterus-leiomyoma
structure, leading to the control of symptoms connected with the disorder without
changes in serum FSH and estradiol.
PMID: 18249392 [PubMed - indexed for MEDLINE]
8: Eur J Obstet Gynecol Reprod Biol. 2008 May;138(1):83-8. Epub 2007 Dec 31.
Effects of letrozole on proliferation and apoptosis in cultured leiomyoma cells
treated with prostaglandin E(2).
Han M, Kim JY, Park JE, Kim JM, Lee KS.
Department of Obstetrics and Gynecology, College of Medicine, Dong-A University,
Busan, South Korea. firstname.lastname@example.org
OBJECTIVE: The objective was to determine the direct effect of letrozole on the
proliferation and apoptosis of cultured leiomyoma cells co-treated with
prostaglandin E(2) (PGE(2)). STUDY DESIGN: Leiomyoma cells were obtained from
three groups of patients who had undergone hysterectomy due to leiomyoma.
Percentages of antiproliferative cells were evaluated by the
3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and
apoptosis was assessed with sub-G1 cell counts by flow cytometry and Western blot
analysis. RESULTS: Combined treatment with 100 microM letrozole and 10 microM
PGE(2) for 48 h resulted in a significantly lower viability rate (25.9+/-4.5%)
and an increased cell death rate (31.6+/-4.4%) than groups treated with letrozole
or PGE(2) alone. However, after adding 10nM estradiol to the combined treatment
group, the cell viability rate was restored (75.1+/-7.7%) and the cell death rate
was decreased (10.5+/-3.1%). Increased caspase-3 expression was found in the
letrozole and PGE(2) combined treatment group, but not in the group in which
estradiol was added. CONCLUSION: The present results demonstrate that letrozole
inhibits growth and induces apoptosis of leiomyoma cells by blocking the
aromatase up-regulated by PGE(2) treatment. These findings support the need for
further investigation of aromatase inhibitors as a medical treatment option in
9: Obstet Gynecol. 2007 Sep;110(3):643-9.
The effect of anastrazole on symptomatic uterine leiomyomata.
Varelas FK, Papanicolaou AN, Vavatsi-Christaki N, Makedos GA, Vlassis GD.
4th Department of Obstetrics and Gynaecology and Department of Biochemistry,
Aristotle University of Thessaloniki, Thessaloniki, Greece. email@example.com
OBJECTIVE: To evaluate the effect of anastrazole on symptomatic uterine
leiomyomata. METHODS: This was a prospective intervention study carried out in a
university department of obstetrics and gynecology. Forty-one premenopausal women
eligible for hysterectomy with 45 uterine leiomyomata were enrolled and treated
with anastrazole 1 mg daily for three cycles of 28 days each. The effect of
treatment was evaluated on leiomyoma and uterine volumes, endometrial thickness,
gonadotrophins, estradiol and hematocrit levels, menstrual pattern, severity of
leiomyoma-related symptoms, and adverse effects. The effects of leiomyoma
location, size, and age of participants on tumor volume changes were evaluated.
RESULTS: Thirty-five women with 39 leiomyomata finished the study. Anastrazole
resulted in a mean 55.7% reduction of leiomyoma volumes (163 mL to 72 mL,
P<.001), a 29.9% reduction in total uterine volumes (278 mL to 195 mL, P<.001),
and an 11.3% increase of the hematocrit levels (33.4% to 37.2%, P<.001) at the
end of the treatment. Leiomyoma location had no significant effect on volume
decrease. Leiomyoma volume decreased in women aged older than 40 years (P=.002),
whereas no difference was found in women younger than 40. The size of large
(greater than 50 mm) leiomyomata decreased significantly (P=.004). Less
difference was observed in small (50 mm or less) leiomyomata (P=.031). No
differences were detected in hormonal status. Anastrazole improved
leiomyoma-related symptomatology and caused no serious adverse effects.
CONCLUSION: In premenopausal women, anastrazole reduces the size of uterine
leiomyomata, improves symptomatology, and is generally well tolerated.
Cliff notes version.
AI works on fibroids in postmenopausal women. CHeck.
Well, it works on premenaopausal women, too, to some degree. Check.
AIs work, even when circulating LH and estradiol levels are not depressed. Huh? Yes, because (1) circulating estradiol may be mainatined from the intact ovary (2) perhaps tissue conversion of T to E is important in the uterus, as elsewhre.
Last, there are other mechanisms of action of the AI, and aromatase and prostaglandin synthesis is new, complex and highly interactive in tissues.