Endometrial cancer risk of Hormonal Contraception

Combination oral contraceptive use was associated with a decreased risk in endometrial carcinoma, which decrease with duration of use (RR=0.28 at 5 years of use); however,  the estimated protective effect was reduced and became statistically non-significant when allowance was made for weight and parity (36,37).

The benefic effect of HC use was only clearly evident in women who had less   than   3   live-births   and   who   had   BMI   less   than   22   kg/m ² (38). Overall, progestin effect is not dose-dependent;  in fact,  high progestin potency HCs did not confer significantly more protection than low progestin potency HCs (OR=0.52). 

However,  among women with a body mass index of 22 kg/m ²  or higher,  those who used high progestin potency oral contraceptives had a lower risk of endometrial cancer than those who used low progestin potency oral contraceptives (OR=0.31)while   those   with   a   BMI   below   22.0   kg/m²  did not (38,39).

A reduced risk of endometrial carcinoma with HCs use was present only among users of five or more years’ duration (40). Oral contraceptives present a chemopreventive opportunity for endometrial cancer and ovarian cancer as risk is dramatically lower among women who have used these preparations than among those who have not So,  the highest protective effect was produced by preparations with the lowest estrogen and the highest progesterone content.

Endometrial cancer risk is not elevated when combined therapy is given in a cyclic manner with progestin administered only part of the time and it is reduced when both oestrogen and progestin are administered on a daily basis (41).

In most cases,  the endometrioid adenocarcinoma of the endometrium is preceded by hyperplasia with different risk of progression into carcinoma.

Two percent of the cases with complex hyperplasia (8/390) progressed into carcinoma and 10.5% into atypical hyperplasia.  Fifty-two percent of the atypical hyperplasias (58/112) progressed into carcinomas. In the case of progestogen treatment (n = 208 cases ) 61.5% showed remission confirmed by re-curetting, compared with 20.3% of the cases without hormonal treatment (n = 182; P

< 0.0001). Endometrial hyperplasia without atypia,it is known respond to hormonal treatment.

In postmenopausal situation, atypical hyperplasia should be treated with total hysterectomy

(42).Endometrial and ovarian cancer are the fourth and fifth most common malignancies in women,  with approximately 40,000 new endometrial and 25,000 new ovarian cancers expected to be diagnosed in the Unites States, per year.  Combined oral contraceptives reduce the risk of endometrial about 50%.

The risk of carcinomas decreases with an increasing duration of oral contraceptive use and this reduced risk lasts for 10-15 years after cessation.  A significantly lower   risk   of   developing   an   endometrial   carcinoma   can   be   observed   for contraceptives with a high progestin and a low estrogen concentration. Due to the protective effect, the use of oral contraceptives is a useful means chemoprevention in   women   at   high   risk   of   endometrial   cancer (43)

Although   intrauterine progesterone therapy has been proposed as a potential uterine-sparing treatment for atypical endometrial hyperplasia and adenocarcinoma, was reported a case of a woman   with   atypical   endometrial   hyperplasia   who   was   treated   with   the levonorgestrel-releasing intrauterine system for 6 months. At follow-up, she was noted to have an increasing endometrial thickness on ultrasonography, and biopsy revealed progression of her lesion to adenocarcinoma (44)

The levonorgestrel-releasing intrauterine system (LNG-IUS) has profound morphologic effects on the endometrium,  including gland atrophy and extensive decidual transformation of the   stroma.  The   findings   confirm   that   the   stromal   compartment   of   the endometrium undergoes changes consistent with decidualization for at least up to 12 months after insertion of an LNG-IUS. There was no correlation between the study end-points and the menstrual patterns reported by some subjects. 

Further study of the decidualized nature of the stromal cells in the LNG-exposed endometrium should enhance understanding of the mechanisms responsible for breakthrough bleeding in users of progestogen-only contraceptives. (45)

Rosa Sabatini and Giuseppe Loverro
Dept. Obstetrics and Gynecology,
General Hospital Policlinico-University of Bari, Italy


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