A comparative study of breast cell proliferation during hormone replacement therapy: effects of tibolone and continuous combined estrogen–progestogen treatment

Conner, Peter; Christow, Alexander; Kersemaekers, Wendy M.; Söderqvist, Gunnar; Skoog, Lambert; Carlström, Kjell; Tani, Edneia; Mol-Arts, Mirjam; Schoultz, Bo von

doi:10.1080/13697130310001651472

Cited by 45 publications

(16 citation statements)

References 19 publications

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“…1). This proliferative response of sequential conjugated equine estrogens-MPA is similar to that of conventional continuous combined treatment found in earlier studies (12,15,21,22) whereas the natural E 2 -P therapy did not increase breast cell proliferation significantly in conformity with previous findings (23). Increased proliferation during HT must be regarded as an unwanted potentially hazardous side effect whereas increased apoptosis reasonably is beneficial.…”

supporting

confidence: 73%

“…The power calculations before the study were based on the assumption of a yield of at least 55% assessable samples both before and after treatment as found by us earlier with fine-needle aspiration biopsies (12,21,24), resulting in the need for 70 women to fulfill the study. However, with core needle biopsy, unexpectedly, only 49% of the women had assessable breast epithelium in biopsies both before and after 2 months of treatment.…”

mentioning

confidence: 99%

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Effects of percutaneous estradiol–oral progesterone versus oral conjugated equine estrogens–medroxyprogesterone acetate on breast cell proliferation and bcl-2 protein in healthy women

Murkes¹,

Conner²,

Leifland³

et al. 2011

Fertility and Sterility

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Effects of percutaneous estradiol-oral progesterone versus oral conjugated equine estrogens-medroxyprogesterone acetate on breast cell proliferation and bcl-2 protein in healthy womenIn a prospective, randomized clinical study 77 women were assigned randomly to receive sequential hormone therapy with either conventional oral conjugated equine estrogens (0.625 mg) with the addition on 14 of the 28 days of oral medroxyprogesterone acetate (5 mg) or natural E 2 gel (1.5 mg) with oral micronized P (200 mg) on 14 of the 28 days of each cycle. Because oral conjugated equine estrogens-medroxyprogesterone acetate induced a highly significant increase in breast cell proliferation in contrast to percutaneous E 2 -oral P with a difference between therapies approaching significance, the former therapy has a marked impact on the breast whereas natural percutaneous E 2 -oral micronized P has not. (Fertil Steril Ò 2011;95:1188-91. Ó2011 by American Society for Reproductive Medicine.)Key Words: Percutaneous estradiol, micronized progesterone, HT, proliferation, bcl-2 protein, normal breast tissue Postmenopausal hormone therapy (HT) has been associated with an increased risk for breast cancer. The risk with combined estrogen-progestogen therapy is greater than with estrogen alone (1-6). Hormone therapy is not a uniform concept, and various preparations, doses, and regimens of HT may have different effects (7). Although estrogen is a known mitogen in the breast, the effects of added progestogens may vary considerably (8-15), but proliferative responses are seen within 2 months (9-11). Synthetic progestogens may differ from natural P. In the French E3N cohort, women taking estrogen in combination with micronized P were found to have no increase in breast cancer risk in contrast to women taking estrogen in combination with synthetic progestogens (16,17).In this study we used core needle biopsy to evaluate breast cell proliferation in healthy postmenopausal women during two different types of sequential HTs: oral conjugated estrogens plus synthetic progestogen versus percutaneous E 2 plus natural oral micronized P. A prospective randomized clinical study was performed at the Karolinska University Hospital, Stockholm, Sweden, between May 2006 and March 2008. Apparently healthy women, aged 44 to 66 years, postmenopausal for at least 12 months, nonsmokers, with normal mammogram results, and with a body mass index of 18 to 30 kg/m 2 , were recruited. Follicle-stimulating hormone levels at screening were >25 IU/L, and E 2 levels <90 pmol/L. The washout period for previous HT users was 3 months.Exclusion criteria were any breast disease, previous breast surgery, hepatic dysfunction, active gallbladder disease, or history of thromboembolic disease. Medication with sexual steroids, barbiturates, carbamazepines, phenytoin, glucocorticoids, rifampicin, cimetidine, diltiazem, erythromycin, ketoconazole, verapamil, and quinidine was not permitted.

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supporting

confidence: 73%

mentioning

confidence: 99%

Effects of percutaneous estradiol–oral progesterone versus oral conjugated equine estrogens–medroxyprogesterone acetate on breast cell proliferation and bcl-2 protein in healthy women

Murkes¹,

Conner²,

Leifland³

et al. 2011

Fertility and Sterility

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“…However, most HTs also have side effects: oestrogen-only therapies stimulate the endometrium, requiring sequential or continuous administration of a progestin resulting in increased vaginal bleeding; oestrogen-only and oestrogen-progestin combinations have been reported to increase the incidence of breast cancer, cardiovascular events and to increase breast tenderness and mammographic density. Tibolone causes in young postmenopausal women, compared to other HT in randomised, controlled trials less vaginal bleeding [15], and less breast tenderness and mammographic density [18], whereas its effects on cardiovascular safety seem not to be different from other HTs [15]. This paper reviews the relationship between endogenous steroids and brain functions with a focus on hormonal treatments, in particular tibolone and on hot flushes, mood, libido and sexual functioning.…”

Section: Observationmentioning

confidence: 98%

Metabolism of exogenous sex steroids and effect on brain functions with a focus on tibolone

Verheul¹,

Kloosterboer²

2006

The Journal of Steroid Biochemistry and Molecular Biology

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“…11 It has an es tro ge nic ac tivity in the cen tral ner vo us system, bo ne, and ge ni tal tis su es, whi le it does not have such ef fects in the bre ast tis su e and en do met ri um, so it is ma inly used for the ma na ge ment of cli mac te ric symptoms in post me no pa u sal wo men. 11,23 Ti bo lo ne in the endo met ri um is ir re ver sibly con ver ted to its ∆-4 isomer that binds to both pro ges te ro ne and an dro gen re cep tors. 11 Ti bo lo ne and its ∆-4 iso mer in du ce estro gen inac ti va ting enz ymes 17β-hydroxy ste ro id dehy dro ge na se and sul fot rans fe ra se, in hi bit sul fata se and en han ce lo cally the de ac ti va ti on of bi o logi cally ac ti ve es tro ge nic me ta bo li tes.…”

Section: Discussionmentioning

confidence: 99%

Therapeutic Efficiency of Tibolone in a Rat Endometriosis Model

Şimşek¹,

Ceyhan²,

Üstün³

et al. 2011

Turkiye Klinikleri J Med Sci

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A AB BS S T TR RA AC CT T O Ob b j je ec c t ti i v ve e: : This study ai med to eva lu a te the the ra pe u tic ef fi ci ency of ti bo lo ne in an ex pe ri men tal rat mo del of in tra-ab do mi nal en do met ri o sis. M Ma a t te e r ri i a al l a an nd d M Me et t h ho od ds s: : In this ex pe rimen tal study, in tra-ab do mi nal en do met ri o sis was in du ced in 30 fe ma le rats sur gi cally. Fo ur we eks af ter this pro ce du re, la pa ro tomy was per for med again. The di men si ons of the en do met ri o sis fo ci were re cor ded and right af ter, the ope ra ti on was comp le ted. Rats we re ran domly di vi ded in to thre e gro ups and sub se qu ently, the tre at ment was star ted. In the first gro up (n= 8), a sing le do se of 1 cc 0.9% NaCl was in jec ted sub cu ta ne o usly. In the se cond gro up (n= 8), in tra mus cu lar in jec ti on of 1 mg le up ro lid ace ta te was ad mi nis te red. In the third gro up (n= 8), 1 mg/kg/day of ti bo lo ne was gi ven by ga va ge. At the end of 4-we eks of drug ad mi nis tra ti on, la pa ro tomy was per for med to all rats. The di men si ons of the en do met ri o sis fo ci we re re cor ded. Af ter wards, all the rats we re sac ri fi ced. The dif fe ren ces in the are as of en do met ri o tic imp lants and ad he si on sco res we re com pa red bet we en the gro ups. R Re e s su ul lt ts s: : The di men si ons of the en do met ri o sis fo ci in the gro ups tre a ted with le up ro lid (p< 0.05) and ti bo lo ne (p< 0.05) we re sig ni fi cantly di mi nis hed compared to that of the con trol gro up. No sta tis ti cally sig ni fi cant dif fe ren ces we re fo und bet we en the tre at ment gro ups. C Co on nc c l lu u s si i o on n: : In a rat en do met ri o sis mo del, ti bo lo ne has a si mi lar ef fi ci ency as that of le up ro lid ace ta te, an agent used for con ven ti o nal me di cal tre at ment of en do met ri o sis. With its an dro ge nic and pro ges ta ge nic charac te ris tics, ti bo lo ne de ser ves at ten ti on as an al ter na ti ve agent in the me di cal tre at ment of en domet ri o sis in hu man. K Ke ey y W Wo or rd ds s: : Rats; endometriosis; gonadotropin-releasing hormone; tibolone Ö ÖZ ZE ET T A Am ma aç ç: : Bu ça lış ma da ka rın içi en do met ri o zis li de ney sel sı çan mo de lin de ti bo lon un te ra pö tik et kin li ği nin de ğer len di ril me si amaç lan dı. G Ge e r re eç ç v ve e Y Yö ön n t te em m l le er r: : Bu de ney sel ça lış ma da, 30 di şi sı çan -da ka rın içi cer ra hi en do met ri o zis mey da na ge ti ril di. Bu iş lem den dört haf ta son ra tekrar la pa ro tomi ya pıl dı. En do met ri o zis odak la rı nın bo yut la rı kay de dil di he men ar dın dan ope ras yon ta mam lan dı. Sı çan lar rast ge le üç gru ba ay rıl dı ve da ha son ra te da vi baş lan dı. Bi rin ci gru ba (n= 8), NaCl 1 cc %0.9 tek doz ola rak cilt al tı na en jek te edil di. İkin ci gru ba (n= 8), le up ro lid ase tat 1 mg in tra mus kü ler ola rak uy gu lan dı. Üçün cü gru ba (n= 8), ti bo lon 1mg/kg/gün ola rak ga vaj ile ve ril di. Dört haf ta ilaç alı mı nın son ra s...

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A comparative study of breast cell proliferation during hormone replacement therapy: effects of tibolone and continuous combined estrogen–progestogen treatment

Abstract: Tibolone seems to have little influence on breast cell proliferation.

Cited by 45 publications

References 19 publications

Effects of percutaneous estradiol–oral progesterone versus oral conjugated equine estrogens–medroxyprogesterone acetate on breast cell proliferation and bcl-2 protein in healthy women

Effects of percutaneous estradiol–oral progesterone versus oral conjugated equine estrogens–medroxyprogesterone acetate on breast cell proliferation and bcl-2 protein in healthy women

Metabolism of exogenous sex steroids and effect on brain functions with a focus on tibolone

Therapeutic Efficiency of Tibolone in a Rat Endometriosis Model

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