Endometrial Morphology During Long-Term Use of Levonorgestrel-Releasing Intrauterine Devices

Silverberg, Steven G.; Haukkamaa, Maija; Arko, Harri; Nilsson, Carl Gustaf; Luukkainen, Tapani

doi:10.1097/00004347-198609000-00005

Cited by 239 publications

(117 citation statements)

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“…A range of endometrial morphologies are found in women using long-term progestogens, including atrophic, highly decidualized and tissue undergoing breakdown (Silverberg et al 1986, Critchley et al 1998a, Vincent et al 1999, Phillips et al 2003. For this reason, we subjected one uterine horn of mice treated with either ENG or LNG to a decidualizing stimulus, while the other remained nondecidualized.…”

Section: Discussionmentioning

confidence: 99%

“…In women using p-only contraceptives, endometrial morphology varies with the type of contraceptive used and the method of progestogen delivery. When high local concentrations of progestogen are delivered to the endometrium using an intrauterine device, such as the LNG-IUS, extensive decidualization and epithelial atrophy were observed and the tissue remains decidualized until the device is removed up to several years later (Silverberg et al 1986, Critchley et al 1998a, 1998b, Phillips et al 2003. However, the decidua induced by artificial stimulation (such as oil injection) in mice, has a finite life span of approximately 8 days before spontaneous breakdown occurs.…”

Section: Discussionmentioning

confidence: 99%

“…The different methods of delivery and local uterine concentrations of progestogen can have differing effects on the morphology of the endometrium. The LNG-IUS produces a high local concentration of progestogen and the endometrium becomes highly decidualized (Silverberg et al 1986), while the slow release subdermal implants result in lower uterine progestogen concentrations and more variable endometrial morphologies. Tissue samples collected from women using Norplant have previously been characterized into three different subtypes: atrophic, shedding and decidualized (p-modified; Marsh et al 1995, Vincent et al 1999, although the bleeding episodes in these women did not directly correlate with the morphology of the tissue (Marsh et al 1995, Vincent et al 1999, Rhoton-Vlasak et al 2005.…”

Section: Introductionmentioning

confidence: 99%

“…Synthetic steroids used in contraceptives influence the endometrium resulting in distinct morphological changes (Silverberg et al 1986, Marsh et al 1995, Hickey et al 1999, Vincent et al 1999, Rhoton-Vlasak et al 2005. It is possible that molecules important for tissue remodelling will be involved in the endometrial changes observed in women using p-only contraceptives and contribute to overall tissue integrity.…”

Section: Introductionmentioning

confidence: 99%

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The long-term actions of etonogestrel and levonorgestrel on decidualized and non-decidualized endometrium in a mouse model mimic some effects of progestogen-only contraceptives in women

Morison¹,

Zhang²,

Kaitu’u-Lino³

et al. 2007

Reproduction

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Breakthrough bleeding (BTB), a major side effect of long-acting progestogen (p)-only contraceptives in women, is the main reason for discontinuation of their use. To understand the mechanisms of BTB, a mouse model of endometrial breakdown and repair was adapted to evaluate the effects of long-term progestogens on the endometrium. Appropriately prepared mice received either an etonogestrel (ENG)-or levonorgestrel (LNG)-releasing subdermal implant. Forty eight hours after decidualization was induced in one uterine horn the majority of tissues were highly decidualized, designated 0 day (0d). Uteri were collected subsequently at 5-day intervals (to 45d) and both decidualized and non-decidualized horns were analysed for morphological changes, leukocyte infiltration and matrix metalloproteinase expression (MMP). In decidualized horns, large blood vessels (BV) developed and disturbance of tissue integrity was observed at 5d with substantial stromal breakdown by 10d, progressing until 25d when re-epithelialization was initiated. By 45d, the tissue was restored to its pre-decidualized state but with considerable tortuosity of the luminal epithelium. Tissue remodelling was not apparent in the non-decidualized horns before 35d, when hyperproliferation of the luminal epithelium resulted in tortuosity. Changes in morphology were similar with the two progestogens, but occurred more rapidly with LNG. Apart from macrophages, few leukocytes were present in non-decidualized horns but large infiltrates of neutrophils and uterine natural killer cells (uNK) were associated with tissue breakdown in decidualized tissue, many of these cells were MMP9-positive. MMP7 was primarily associated with tissue repair. Therefore, this model mimics some of the changes observed in endometria of women using p-only contraceptives and provides an opportunity for functional studies.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

The long-term actions of etonogestrel and levonorgestrel on decidualized and non-decidualized endometrium in a mouse model mimic some effects of progestogen-only contraceptives in women

Morison¹,

Zhang²,

Kaitu’u-Lino³

et al. 2007

Reproduction

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“…It has been proven to reduce the amount and duration of menstrual blood loss [15,16] by inhibiting endometrial proliferation [17]. However, large uterine size increases the risk of expulsion and decreases its efficacy [18].…”

Section: Levonorgestrel-releasing Intrauterine Devicesmentioning

confidence: 99%

Medical Management of Uterine Fibroids

Parsanezhad

Jahromi

2012

Curr Obstet Gynecol Rep

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Uterine leiomyomas are the most common benign tumors of the uterus. Though benign, they can affect the quality of life for many women. Compared with the standard surgical treatments, medical therapy is attractive and avoids possible surgery-related complications. No medical therapy currently exists that can induce rapid regression of the myoma and symptoms with minimal side effects without affecting fertility. This review evaluates medical treatments that are currently available for the treatment of uterine fibroids.

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Progestogen-releasing intrauterine systems versus other forms of reversible contraceptives for contraception

French

Sorhaindo

Vliet

et al. 2004

Cochrane Database of Systematic Reviews

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Endometrial Morphology During Long-Term Use of Levonorgestrel-Releasing Intrauterine Devices

Cited by 239 publications

References 0 publications

The long-term actions of etonogestrel and levonorgestrel on decidualized and non-decidualized endometrium in a mouse model mimic some effects of progestogen-only contraceptives in women

The long-term actions of etonogestrel and levonorgestrel on decidualized and non-decidualized endometrium in a mouse model mimic some effects of progestogen-only contraceptives in women

Medical Management of Uterine Fibroids

Progestogen-releasing intrauterine systems versus other forms of reversible contraceptives for contraception

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