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      Progestogens in menopausal hormone therapy

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          Abstract

          Progestogens share one common effect: the ability to convert proliferative endometrium to its secretory form. In contrast, their biological activity is varied, depending on the chemical structure, pharmacokinetics, receptor affinity and different potency of action. Progestogens are widely used in the treatment of menstrual cycle disturbances, various gynaecological conditions, contraception and menopausal hormone therapy. The administration of progestogen in menopausal hormone therapy is essential in women with an intact uterus to protect against endometrial hyperplasia and cancer. Progestogen selection should be based on the characteristics available for each progestogen type, relying on the assessment of relative potency of action in experimental models and animal models, and on the indirect knowledge brought by studies of the clinical use of different progestogen formulations. The choice of progestogen should involve the conscious use of knowledge of its benefits, with a focus on minimizing potential side effects. Unfortunately, there are no direct clinical studies comparing the metabolic effects of different progestogens.

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          Meta-analysis: effect of hormone-replacement therapy on components of the metabolic syndrome in postmenopausal women.

          E. Salpeter, Christine S. Walsh, E Greyber … (2006)
          To quantify the effects of hormone-replacement therapy (HRT) on components of the metabolic syndrome in postmenopausal women. Comprehensive searches of electronic databases were performed from April 1966 to October 2004. We included randomized controlled trials that were of at least 8 weeks duration and evaluated the effect of HRT on metabolic, inflammatory or thrombotic components. Insulin resistance was calculated by homeostasis model assessment (HOMA-IR). Subgroup analysis evaluated the effects for transdermal and oral treatment and for diabetic and non-diabetic women. Pooled results of 107 trials showed that HRT reduced abdominal fat [-6.8% (CI, -11.8 to -1.9%)], HOMA-IR [-12.9% (CI, -17.1 to -8.6%)] and new-onset diabetes [relative risk 0.7 (CI, 0.6-0.9)] in women without diabetes. In women with diabetes, HRT reduced fasting glucose [-11.5% (CI, -18.0 to -5.1%)] and HOMA-IR [-35.8% (CI, -51.7 to -19.8%)]. HRT also reduced low-density lipoprotein/high-density lipoprotein cholesterol ratio [-15.7% (CI, -18.0 to -13.5%)], lipoprotein(a) [Lp(a)] [-25.0% [CI, -32.9 to -17.1%)], mean blood pressure [-1.7% (CI, -2.9 to -0.5%)], E-selectin [-17.3% (CI, -22.4 to -12.1%)], fibrinogen [-5.5% (CI, -7.8 to -3.2%)] and plasminogen activator inhibitor-1 [-25.1% (CI, -33.6 to -15.5%)]. Oral agents produced larger beneficial effects than transdermal agents, but increased C-reactive protein (CRP) [37.6% (CI, 17.4-61.3%)] and decreased protein S [-8.6% CI, -13.1 to -4.1%)], while transdermal agents had no effect. HRT reduces abdominal obesity, insulin resistance, new-onset diabetes, lipids, blood pressure, adhesion molecules and procoagulant factors in women without diabetes and reduced insulin resistance and fasting glucose in women with diabetes. Oral agents adversely affected CRP and protein S, while transdermal agents had no effects.
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            Classification and pharmacology of progestins.

            René Druckmann, Carlo Campagnoli, Karl W Schweppe … (2003)
            Besides the natural progestin, progesterone, there are different classes of progestins, such as retroprogesterone (i.e. dydrogesterone), progesterone derivatives (i.e. medrogestone) 17alpha-hydroxyprogesterone derivatives (i.e. chlormadinone acetate, cyproterone acetate, medroxyprogesterone acetate, megestrol acetate), 19-norprogesterone derivatives (i.e. nomegestrol, promegestone, trimegestone, nesterone), 19-nortestosterone derivatives norethisterone (NET), lynestrenol, levonorgestrel, desogestrel, gestodene, norgestimate, dienogest) and spironolactone derivatives (i.e. drospirenone). Some of the synthetic progestins are prodrugs, which need to be metabolized to become active compounds. Besides the progestogenic effect, which is in common for all progestins, there is a wide range of biological effects, which are different for the various progestins and have to be taken into account, when medical treatment is considered.
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              Breast cancer risk in relation to different types of hormone replacement therapy in the E3N-EPIC cohort.

              V Avenel, Elio Riboli, Françoise Clavel-Chapelon … (2005)
              Most epidemiological studies have shown an increase in breast cancer risk related to hormone replacement therapy (HRT) use. A recent large cohort study showed effects of similar magnitude for different types of progestogens and for different routes of administration of estrogens evaluated. Further investigation of these issues is of importance. We assessed the risk of breast cancer associated with HRT use in 54,548 postmenopausal women who had never taken any HRT 1 year before entering the E3N-EPIC cohort study (mean age at inclusion: 52.8 years); 948 primary invasive breast cancers were diagnosed during follow-up (mean duration: 5.8 years). Data were analyzed using multivariate Cox proportional hazards models. In this cohort where the mean duration of HRT use was 2.8 years, an increased risk in HRT users compared to nonusers was found (relative risk (RR) 1.2 [95% confidence interval 1.1-1.4]). The RR was 1.1 [0.8-1.6] for estrogens used alone and 1.3 [1.1-1.5] when used in combination with oral progestogens. The risk was significantly greater (p <0.001) with HRT containing synthetic progestins than with HRT containing micronized progesterone, the RRs being 1.4 [1.2-1.7] and 0.9 [0.7-1.2], respectively. When combined with synthetic progestins, both oral and transdermal/percutaneous estrogens use were associated with a significantly increased risk; for transdermal/percutaneous estrogens, this was the case even when exposure was less than 2 years. Our results suggest that, when combined with synthetic progestins, even short-term use of estrogens may increase breast cancer risk. Micronized progesterone may be preferred to synthetic progestins in short-term HRT. This finding needs further investigation. (c) 2004 Wiley-Liss, Inc.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Prz Menopauzalny
                Journal ID (iso-abbrev): Prz Menopauzalny
                Journal ID (publisher-id): MR
                Title: Przegla̜d Menopauzalny = Menopause Review
                Publisher: Termedia Publishing House
                ISSN (Print): 1643-8876
                ISSN (Electronic): 2299-0038
                Publication date (Electronic): 22 June 2015
                Publication date (Print): June 2015
                Volume: 14
                Issue: 2
                Pages: 134-143
                Affiliations
                [1 ]1 st Department of Obstetrics and Gynaecology, Centre of Postgraduate Medical Education, Warsaw, Poland
                [2 ]Department of Clinical Pharmacology, Chair of Pharmacology, Faculty of Medicine, Jagiellonian University Medical College, Cracow, Poland
                Author notes
                Corresponding author: Małgorzata Bińkowska, 1 st Department of Obstetrics and Gynecology, Centre of Postgraduate Medical Education, 231 Czerniakowska St., 00-416 Warsaw, Poland. e-mail: mabi@ 123456onet.pl
                Article
                Publisher ID: 25232
                DOI: 10.5114/pm.2015.52154
                PMC ID: 4498031
                SO-VID: e44563cc-58a3-4db3-8dee-aec219e009b9
                Copyright © Copyright © 2015 Termedia
                License:

                This is an Open Access article distributed under the terms of the Creative Commons Attribution-Noncommercial 3.0 Unported License, permitting all non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 29 April 2015
                Date revision received : 08 May 2015
                Date accepted : 01 June 2015
                Categories
                Subject: Review Paper

                Keywords: progestogens,menopausal hormone therapy,progesterone,progestin
                Data availability:
                Keywords: progestogens, menopausal hormone therapy, progesterone, progestin

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