Uterus
Non tumor
Exogenous hormones

Author: Nat Pernick, M.D. (see Authors page)

Revised: 19 January 2017, last major update January 2012

Copyright: (c) 2002-2017, PathologyOutlines.com, Inc.

PubMed search: exogenous [title] hormones uterus

Cite this page: Exogenous hormones. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/uterusexogenoushor.html. Accessed August 19th, 2017.
Hormonal therapy in the past
  • Associated with pulmonary emboli, thrombophlebitis (intimal thickening with endothelial proliferation)
  • Less likely now due to smaller hormonal doses (Mod Pathol 2000;13:285)
Oral contraceptives
  • Have small doses of estrogen and progesterone

Micro description:
  • Endometrial glandular arrest with small, straight and inactive glands, no mitotic figures and usually no secretions
  • Glands are lined by immature epithelial cells
  • Cytoplasm has randomly distributed vacuoles and smooth, well defined apical border
  • Nuclei lack thick nuclear membrane or coarse chromatin seen in proliferative endometrium
  • Glands may have dense eosinophilic secretion (abortive secretion)
  • Stroma initially edematous, then decidual with granulocytic infiltrates
  • Vessels are thin, later become dilated and lack changes of spiral arterioles (thickening, coiling) at day 23
  • Also endocervical microglandular hyperplasia and squamous metaplasia
  • Prolonged use: disappearance of abortive glandular secretion, atrophy of glands and stroma

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Atrophic epithelium, stromal
decidual reaction, thin
dilated blood vessels

High potency progesterone oral contraceptive
  • Used for endometrial hyperplasia

Micro description:
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Small inactive glands,
hyperplastic stroma,
thickened blood vessels

Ovulation induction therapy
  • Used to treat ovulation failure (irregular or infrequent ovulation or chronic anovulation due to deficient gonadotropins or their inability to stimulate follicle maturation)
  • In polycystic ovary disease patients, may see endometrial hyperplasia with secretory changes of glands and stroma, or rarely carcinoma

Micro description:
  • Dyssynchronous endometrium (stromal maturation [day 22 - 23] more advanced than glandular maturation [day 16 - 17])

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Stroma more mature
than endometrial glands

Estrogens alone for hormone replacement therapy
  • Hormone replacement for menopause, premature ovarian failure, post oophorectomy and Turner's syndrome
  • Causes hyperplasia with variable atypia in 15% of postmenopausal women; also increased risk (4 - 8×) of endometrial carcinoma, usually superficial and well differentiated with excellent prognosis; also increased risk of breast neoplasms
  • Adding progesterone protects the endometrium and reduces risk of hyperplasia and carcinoma
  • Compared to oral contraceptives, uses lower dosage and different estrogens

Micro description:
  • Proliferative or weakly proliferative endometrium, often with stromal breakdown; endometrial hyperplasia (simple or complex, with or without atypia), occasional squamous metaplasia (squamoid morules), stromal foam cells; endometrial polyps with hyperplastic changes
  • Changes may persist after therapy ends

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Endometrial
complex glandular
hyperplasia with
squamoid morules

Same patient after combined therapy

Combined hormone replacement therapy
  • Variable changes, often with mixed proliferative and secretory endometrium
  • May resemble endometrial carcinoma

Micro description:
  • Glands may be crowded or hyperplastic with edematous, hyperplastic or decidualized stroma; also tubal, eosinophilic, mucinous or papillary metaplasia; also changes of shedding

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Mixed endometrium: secretory
endometrium with focally
hyperplastic glands

Lupron for leiomyomas
  • Gonadotropin releasing hormone agonist that usually reduces size of uterine leiomyomas by suppressing estrogen stimulation and inducing a temporary menopause

Micro description:
  • Leiomyomas initially show edema and necrosis, then hyalinization and mild lymphocytic infiltrate
  • Endometrium becomes weakly proliferative, later inactive and later atrophic
Progestational agents
  • Used for endometrial hyperplasia and neoplasia, particularly in young women who don't want hysterectomies or are poor surgical candidates

Micro description:
  • Lack of glandular proliferation; endometrium appears quiescent with no mitotic activity
  • Presence of secretory changes in glands, decidual stroma
  • Note: hyperplasia and carcinoma may persist in sampled or unsampled endometrium
  • Differential diagnosis: pregnancy (glands not atrophic), sarcoma (nuclear atypia)
Selective progesterone receptor modulators
  • Drugs with progesterone antagonist activity (example: CDB-4124, also known as Proellex) that may confer therapeutic benefit for reproductive disorders (endometriosis, leiomyomas) in premenopausal women
  • Produces "progesterone receptor modulator associated endometrial changes"

Micro description:
  • Inactive or atrophic endometrium, less frequently proliferative or secretory (Mod Pathol 2009;22:450)
  • Cystically dilated glands, secretory changes coexisting with mitoses and apoptotic bodies
  • With increasing dose and exposure, epithelium becomes more atrophic and cysts more prominent
  • May resemble disordered proliferative or hyperplastic endometrium
  • Not associated with endometrial hyperplasia or carcinoma (Mod Pathol 2008;21:591)
  • Mifepristone related changes include nonsynchronous endometrium, large fluid filled glands, and abnormal blood vessels (Hum Pathol 2011;42:947)


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Endometrial changes


Vascular changes

Tamoxifen
  • Used for breast cancer treatment / prevention
  • Binds to estrogen receptors with both agonist and antagonist effects
  • Associated with endometrial carcinoma (well to poorly differentiated, may have irregular glandular changes) and MMMT

Gross description:
  • Uterine size up to 1 kg

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Diffuse adenomyosis,
myometrial hyperplasia,
endometrial polyps



Micro description:
  • Polypoid endometrial proliferation with glandular hyperplasia (simple, complex and with or without atypia), mucinous and squamous metaplasia, fibrotic stroma, diffuse smooth muscle hyperplasia, leiomyomas and adenomyosis; also inactive or atrophic changes
  • May produce small blue cells on Pap smear (Arch Pathol Lab Med 2001;125:1047)

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Mucinous and squamous
metaplasia, resembling
endocervical tissue

Fig 1: exuberant pinkish tan, friable, bosselated soft tissue bulging into endometrial cavity
Fig 2 / 3: cystic atrophy of glands with diffuse infiltration of the endometrial stroma by large
polyhedral eosinophilic cells, sparse lymphoplasmacellular infiltrate, occasional eosinophils, no atypia