The major biologically active circulating estrogen in both males and females is estradiol (E2). Circulating E2 is a product of the ovarian granulosa cell and the testicular Leydig cell. Its gonadal formation is dependent on A-ring aromatization of its immediate precursor, testosterone, by a particular isoform of the enzyme aromatase, which also catalyses the conversion of the much weaker androgen, androstenedione, to the weak estrogen, estrone. E2 is also formed in non-gonadal tissues, such as adipose tissue, liver, muscle and brain. Only adipose tissue makes significant extra-gonadal contributions to circulating estrogen. Loss of ovarian function during reproductive life, as a result of loss of gonadotropin secretion (secondary hypogonadism) or as a result of premature ovarian failure (generally defined as cessation of ovarian function prior to age 40), results in loss of the majority of circulating E2 and of luteal progesterone. Loss of ovarian function at the menopause likewise results in a 90% loss of circulating E2. The consequences of loss of ovarian function during reproductive life may be severe. Symptoms include hot flushes, night sweats, vaginal dryness and dyspareunia, loss of libido, loss of bone mass with subsequent osteoporosis and abnormalities of cardiovascular function, including a substantial increase in the risk of ischemic heart disease. Various regimens of estrogen replacement have been employed, aiming to eliminate symptoms, restore well-being and avert the consequences of estrogen depletion. The commonly adopted form of replacement is with the low-dose oral contraceptive pill for reasons of convenience, cost, efficacy, general freedom from side effects and the psychological advantage that many of the patient’s peer group are also ‘taking the pill’. An often neglected aspect of hormone therapy in the reproductive age group is the therapeutic use of testosterone. The application of such principles to the postmenopausal period is more problematic, as there is a common perception that the menopause is a normal physiological occurrence and that it is therefore not physiological to offer hormone therapy at that time. The pragmatic approach is to recommend standard therapy with estrogen and progestogen for the management of menopausal symptoms and to recommend longer term hormone replacement in the light of the individual’s needs and current data with regard to efficacy for protection from osteoporosis and cardiovascular disease.

Journal Section:
Paper
Keywords:
Estrogens, Progestogens, Puberty, Menopause, Premature menopause
1.
Burger HG, Dudley, E, Mamers P, Groome N, Robertson DM: Early follicular phase serum FSH as a function of age: the roles of inhibin B, inhibin A and estradiol. Climacteric 2000;3:17–24.
[PubMed]
2.
Burger HG, Dudley EC, Hopper JL, Groome N, Guthrie JR, Green A, Dennerstein L: Prospectively measured levels of serum FSH, estradiol and the dimeric inhibins during the menopausal transition in a population-based cohort of women. J Clin Endocrinol Metab 1999;84(11):4025–4030.
3.
Grodin JM, Siiteri PK, Macdonald PC: Sources of estrogen production in postmenopausal women. J Clin Endocrinol Metab 1973;36:207–214.
[PubMed]
4.
Aran O, Galatzer A, Kauli R, Nagelberg N, Robicsek Y, Laron Z: Social, educational and vocational status of 48 young adult females with gonadal dysgenesis. Clin Endocrinol (Oxf) 1992;36(4):405–410.
5.
Ross JL, McCauley E, Roeltgen D, Long L, Kushner H, Feuillan P, Cutler GB Jr: Self-concept and behavior in adolescent girls with Turner syndrome: potential estrogen effects. J Clin Endocrinol Metab 1996;81:926–931.
[PubMed]
https://doi.org/10.1210/jc.81.3.926
6.
Elsheikh M, Conway GS: The impact of obesity on cardiovascular risk factors in Turner’s syndrome. Clin Endocrinol 1998;49:447–450.
7.
Rosenberg L, Hennekens CH, Rosner B, Belanger C, Rothman KJ, Speizer L: Early menopause and the risk of myocardial infarction. Am J Obstet Gynecol 1981;139:47–51.
[PubMed]
8.
Guttman H, Weiner Z, Nikolski E, Ish-Shalom S, Itskovitz-Eldor J, Aviram M, Reisner S, Hochberg Z: Choosing an oestrogen replacement therapy in young adult women with Turner syndrome. Clin Endocrinol 2001;54:159–164.
9.
Burger HG, Hailes J, Nelson J, Menelaus M: Effect of combined implants of oestradiol and testosterone on libido in postmenopausal women. Br Med J 1987;94:936–937.
10.
Shifren J, Braunstein GD, Simon JA, Casson PR, Buster JE, Redmond GP, Burki RE, Ginsburg ES, Rosen RC, Leiblum SR, Caramelli KE, Mazer NA: Transdermal testosterone treatment in women with impaired sexual function after oophorectomy. N Engl J Med 2000;343:682–688.
[PubMed]
https://doi.org/10.1056/NEJM200009073431002
11.
Karjalainen A, Paassilta M, Heikkinen A-C, Backstrom AC, Savolainen M, Kesaniemi YA: Effects of peroral and transdermal oestrogen replacement therapy on glucose and insulin metabolism. Clin Endocrinol 2001;54:165–173.
12.
Ho KY, Weissberger AJ: Impact of short-term oestrogen administration on growth hormone secretion and action: distinct route-dependent effects on connective and bone tissue metabolism. J Bone Miner Res 1992;7:821–827.
[PubMed]
13.
Roussow JE: Does estrogen have a role in the prevention of cardiovascular disease? J Clin Endocrinol Metab 1999;84:1806–1810.
14.
Hulley S, Grady D, Bush T, Furberg C, Herrington D, Riggs B, Vittinghoff E: Randomized trial of estrogen plus progestin for secondary prevention of coronary heart disease in postmenopausal women. Heart and Estrogen/progestin Replacement Study (HERS) Research Group. J Am Med Assoc 1998;280:605–613.
[PubMed]
© 2001 S. Karger AG, Basel
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2001
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