Abstract
Humans are almost unique in nature, having a long post-menopausal life span without ovarian steroid hormones. Most female organs possess estrogen receptors and many have progesterone receptors, implying that these organs are influenced by sex hormones even after cessation of ovarian steropidogenesis. Due to the side effects of estrogen withdrawal at the menopause, estrogen replacement therapy has been widely used for the past 50 years. However, due to the proliferative effect of estrogen on the endometrium leading to hyperplasia and cancer, progestogens are added to counteract the effect of estrogen on the endometrium. However, progestogens have their beneficial and side effects. The main side effect of progestogens is breast cancer as described in Chap. 11. The main side effects of the menopause are osteoporosis and hot flushes. Progestogens have a minimal effect on bone mineral density, but act synergistically with estrogen to reduce hot flushes. Additionally, progestogens, particularly those with antiestrogenic actions, reduces the increased risk of venous thrombo-embolus which is associated with estrogens. Progesterone is a neurosteroid, in addition to its reproductive function. As such it is neuroprotective preventing demyelinization in the central and peripheral nervous systems, and protects against Alzheimer’s disease. In this chapter some of the scientific data that connects progestogens to effects of the menopause are discussed.
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References
Ziel HK, Finkle WD. Association of estrone with the development of endometrial carcinoma. Am J Obstet Gynecol. 1976;124(7):735–40.
Rossouw JE et al. Risks and benefits of estrogen plus progestin in healthy postmenopausal women. Principal results from the Women’s Health Initiative randomized controlled study. JAMA. 2002;288:321–33.
Beral V. Breast cancer and hormone-replacement therapy in the Million Women Study. Lancet. 2003;362:419–27.
Fournier A et al. Breast cancer risk in relation to different types of hormone replacement therapy in the E3N-EPIC cohort. Int J Cancer. 2005;114:448–54.
Feeser VR, Loria RM. Modulation of traumatic brain injury using progesterone and the role of glial cells on its neuroprotective actions. J Neuroimmunol. 2011;237:4–12.
Stein DG, Wright DW. Progesterone in the clinical treatment of acute traumatic brain injury. Expert Opin Investig Drugs. 2010;19:847–57.
Blackmore PF et al. Cell surface-binding sites for progesterone mediated calcium-uptake in human sperm. J Biol Chem. 1991;266:18655–9.
Zhu Y et al. Cloning, expression, and characterization of a membrane progestin receptor and evidence it is an intermediary in meiotic maturation of fish oocytes. Proc Natl Acad Sci U S A. 2003;100:2231–6.
Prior FC. Progesterone as a bone-trophic hormone. Endocr Rev. 1990;11:386–98.
Clark MK et al. Bone mineral density loss and recovery during 48 months in first-time users of depo medroxyprogesterone acetate. Fertil Steril. 2006;86:1466–74.
Delmas PD et al. A combination of low doses of 17 beta-estradiol and northisterone acetate prevents bone loss and normalizes bone turnover in postmenopausal women. Osteoporos Int. 2000;11:177–87.
Schoonen WG et al. Hormonal properties of norethisterone, 7alpha-methyl-norethisterone and their derivates. J Steroid Biochem Mol Biol. 2000;74:213–22.
Broulik PD et al. Progestagens androgenic action on the bone of male castrated mice. Prague Med Rep. 2006;107:401–8.
Yao W et al. Inhibition of nuclear receptor during the bone linear growth phase increases peak bone mass in female mice. PLoS One. 2010;5:e11410.
Hitchcock CL, Prior JC. Oral micronized progesterone for vasomotor symptoms. A placebo-controlled randomized trial in healthy postmenopausal women. Menopause. 2012;10(1097).
Prior JC, Hitchcock CL. Progesterone for hot flush and night sweat treatment- effectiveness for severe vasomotor symptoms and lack of withdrawal rebound. Gynecol Endocrinol. 2012;28(s2):7–11.
Prior JC, Nielsen JD, et al. Medroxyprogesterone and conjugated oestrogen are equivalent for hot flushes: a 1-year randomized Double-blind trial following premenopausal overiectomy. Clin Sci (Lond). 2007;112:517–25.
Loprinzi CL et al. Megesterol acetate for the prevention of hot flashes. N Engl J Med. 1994;331:347–52.
Dennerstein L et al. Menopausal hot flashes: a double blind comparison of placebo, ethinyl estardiol and norgestrel. Br J Obstet Gynaecol. 1978;85:852–6.
Freedman RR. Biochemical, metabolic, and vascular mechanisms in menopausal hot flushes. Fertil Steril. 1998;70:332–7.
Olie V et al. Risk of venous thrombosis with oral versus transdermal estrogen therapy among postmenopausal women. Curr Opin Hematol. 2010;17:457–63.
Stanczyk FZ et al. Progestogens used in postmenopausal hormone therapy: differences in their pharmacological properties, intracellular actions and clinical effects. Endocr Rev. 2013;34:171–208.
Canonico M et al. Hormone therapy and venous thromboembolism among postmenopausal women: impact of the route of estrogen administration and progestogens: the ESTHER study. Circulation. 2007;115:840–5.
Chen S et al. Allopregnanolone promotes regeneration and reduces β-amyloid burden in a preclinical model of Alzheimer’s disease. PLoS One. 2011;6:e24293.
Brinton RD, Wang JM. Therapeutic potential of neurogenesis for prevention and recovery from Alzheimer’s disease: allopregnanolone as a proof of concept neurogenic agent. Curr Alzheimer Res. 2006;3:185.
Kuhl H. Pharmacology of estrogens and progestogens: influence of different routes of administration. Climacteric. 2005;8(suppl):3–63.
Chuang DM et al. GSK-3 as a target for lithium induced neuroprotection against excitotoxicity in neural cultures and animal models of ischemic stroke. Front Mol Neurosci. 2011;4:15T.
Garay LI et al. Progesterone down-regulates spinal cord inflammatory mediators and increases myelination in experimental autoimmune encephalomyelitis. Neuroscience. 2012;226:40–50.
Compagnone NA, Mellon SH. Neorosteroids: biosynthesis - and function of these novel neoromodulators. Front Neuroendocrinol. 2000;21:1–58.
Mellon SH. Neurosteroid regulation of CNS development. Pharmacol Ther. 2007;116:107–24.
Micevych P, Soma KK, Sinchak K. Neuroprogesterone; key to estrogen positive feedback? Brain Res Rev. 2008;57(2):470–80.
Wang JM et al. Regenerative potential of allopregnanolone. Brain Res Rev. 2008;57:398–409.
Herson PS et al. Sex, sex steroids and brain injury. Semin Reprod Med. 2009;27:229–39.
Roof RL et al. Progesterone facilitates cognitive recovery and reduces secondary neuronal loss caused by cortical contusion injury in male rats. Exp Neurol. 1994;129:64–9.
Wright DW et al. ProTECT: a randomized clinical trial of progesterone for acute traumatic brain injury. Ann Emerg Med. 2007;49:391–402.
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Pe’er, E. (2015). Progestogens and the Menopause. In: Carp, H. (eds) Progestogens in Obstetrics and Gynecology. Springer, Cham. https://doi.org/10.1007/978-3-319-14385-9_12
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DOI: https://doi.org/10.1007/978-3-319-14385-9_12
Publisher Name: Springer, Cham
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