2 McCowan L, Stewart A. Term birthweight centiles for babies from New

Zealand’s main ethnic groups. Aust N Z J Obstet Gynaecol 2004;

44:432–35.

3 McCowan L, Harding J, Stewart AW. Customised birthweight centiles

predict SGA pregnancies with perinatal morbidity. BJOG 2005;112:

1026–33.

Lesley McCowanDepartment of Obstetrics and Gynaecology, University of Auckland,

New Zealand.

DOI: 10.1111/j.1471-0528.2005.00832.x

Re: The use of levonorgestrel-releasing

intrauterine system for the treatment of

menorrhagia in women with inherited

bleeding disorders

Sir,

We write in response to the correspondence letter on

the above article by Wahab and Al-Azzawi.1 Wahab and

Al-Azzawi claim that ‘the LNG IUS is associated with high

systemic absorption of the progestogen, and serum levels of

levonorgestrel (LNG) have been recorded around 511 pmol/L.

This is equivalent to two LNG-containing minipill tablets

daily continuously’. However, Wahab and Al-Azzawi would

appear to have misinterpreted the units used.

The systemic serum level of levonorgestrel (LNG) in fertile

aged women using the levonorgestrel-releasing intrauterine

system (LNG IUS) is 150–200 pg/ml.2 The citation of LNG

levels of 511 pmol/l that Wahab and Al-Azzawi have used is

correct but corresponds to approximately 160 pg/ml. There is

no published pharmacokinetic data that show similar LNG

levels during the use of LNG IUS and two LNG-containing

minipill tablets daily continuously, and we are not aware such

data exist.

Wahab and Al-Azzawi also claim that ‘. a wealth of

biological data show that progesterone and progestogens in

general and LNG in particular being established mammary

epithelial mitogens’. However, no references are given to sup-

port this statement. Neither in a large cohort study of LNG

implant users3 nor in a case–control study with progestin-

only injectables or implant users4 was an elevated risk of

breast cancer found. In 2005, an epidemiological study on

more than 17 000 LNG IUS users did not indicate an in-

creased risk of breast cancer, as compared with overall breast

cancer incidence.5 The gathered data do not, therefore, sup-

port an association of the LNG IUS use and the development

of breast cancer.

The statement that ‘the LNG-IUS also suppresses oestrogen

production, inducing a clinical situation not unlike a prema-

ture menopause in at least 50% of treated women’ is also not

referenced. It has been clearly shown that use of the LNG IUS

is not associated with suppression of endogenous estradiol

production.6 Most women using the LNG IUS have ovulatory

cycles, implying normal endogenous estradiol production.2,6,7

Therefore, a deleterious effect on bone mineral density (BMD)

is not plausible.

In a randomised comparative trial of 236 women with

menorrhagia (mean age 43 years, range 35–49 years) treated

with the LNG IUS or hysterectomy, hysterectomised women

had a significantly higher mean follicle-stimulating hormone

(FSH) level (13.8 iu/ml) than women treated with the LNG

IUS (9.2 iu/ml, P = 0.005) at 1 year of follow up.8 Hot flushes

increased significantly in the hysterectomy group (P = 0.02),

with no change in the LNG IUS group.8 In the LNG IUS

group, FSH decreased (–1.9 iu/ml) among younger women

(<43 years) and increased slightly and consistently with aging

(+1.3 iu/ml) in older women (>43 years). The corresponding

levels of FSH in the hysterectomised women were +1.5 iu/ml

(women <43 years) and +8.0 iu/ml (women >43 years).8

The results suggest that hysterectomy, but not LNG IUS

use, may impair ovarian function.8 Regarding BMD, the same

study has shown that the annual decrease in lumbar spine

BMD was significantly greater in the hysterectomy group

(–0.24%) compared with the LNG IUS group (–0.06%, P =

0.02) at 5 years of follow up, suggesting that hysterectomy

may accelerate age-related loss of BMD.9

The comment ‘patients and doctors should be warned about

the metabolic and carcinogenic risks’ is to be questioned.

Data clearly demonstrate the low systemic serum level of

LNG associated with the LNG IUS use. Available data do not

support an association of the LNG IUS use or progestin-only

injectables or implants and the development of breast cancer.

The use of the LNG IUS is not associated with decreased

endogenous estradiol levels, and there is no suggestion that

use of the LNG IUS is associated with loss of BMD. j

References

1 Wahab M, Al-Azzawi F. The use of levonorgestrel-releasing intrauterine

system for the treatment of menorrhagia in women with inherited

bleeding disorders. BJOG 2005;112:1455–6.

2 Luukkainen T, Lahteenmaki P, Toivonen J. Levonorgestrel-releasing

intrauterine device. Ann Med 1990;22:85–90.

3 International Collaborative Post-Marketing Surveillance of Norplant.

Post-marketing surveillance of Norplant contraceptive implants: I.

Contraceptive efficacy and reproductive health. Contraception

2001;63:167–86.

4 Strom BL, Weber AL, Norman SA, Bernstein L, Burkman RT, Daling JR,

et al. Absence of an effect of injectable and implantable progestin-

only contraceptives on subsequent risk of breast cancer. Contracep-

tion 2004;69:353–60.

5 Backman T, Rauramo I, Jaakkola K, Inki P, Vaahtera K, Launonen A,

et al. Use of the levonorgestrel-releasing intrauterine system and

breast cancer. Obstet Gynecol 2005;106:813–817.

6 Nilsson CG, Lahteenmaki PL, Luukkainen T. Ovarian function in

amenorrheic and menstruating users of a levonorgestrel-releasing

intrauterine device. Fertil Steril 1984;41:52–55.

248 ª RCOG 2006 BJOG An International Journal of Obstetrics and Gynaecology

Correspondence

7 Barbosa I, Olsson SE, Odlind V, Goncalves T, Coutinho E. Ovarian

function during use of a levonorgestrel-releasing IUD. Contraception

1990;42:51–66.

8 Halmesmaki K, Hurskainen R, Tiitinen A, Teperi J, Grenman S, Kivela A,

et al. A randomised controlled trial of hysterectomy or the levonorges-

trel-releasing intrauterine system in the treatment of menorrhagia—

effect on FSH levels and menopausal symptoms. Hum Reprod

2004;19:378–82.

9 Halmesmaki K, Paavonen J, Tuppurainen M, Hurskainen R. A rando-

mised controlled trial of the effect of hysterectomy or levonorgestrel-

releasing intrauterine system on bone mineral density in menorrhagia

patients—a five-year follow-up (Abstract). Sixth Congress of the Euro-

pean Society of Gynecology; 2–4 Jun 2005.

Rebecca Curtisa & Pirjo InkibaGynaecology and Andrology, Schering, West Sussex, UKbSchering Oy, Turku, Finland

DOI: 10.1111/j.1471-0528.2005.00842.x

ª RCOG 2006 BJOG An International Journal of Obstetrics and Gynaecology 249

Correspondence