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Actions of Progesterone |
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The Actions of Progesterone |
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In women, progesterone is a steroid
hormone produced primarily by the ovaries and adrenal glands. Progesterone
has a direct affect on the function of the reproductive system, the nervous
system, the cardiovascular system and the skeletal system. |
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Blood sugar levels, skin and other
tissues and functions are also significantly influenced by progesterone. Like all steroid hormones, excessive amounts of
progesterone can contribute to a number of increased health risks. |
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Though proper progesterone levels are critical for the
prevention of endometrial hyperplasia |
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and endometrial cancer, the actions of this hormone extend
far beyond endometrial health. Therefore it is crucial that proper levels
also be maintained in women who have had a hysterectomy. |
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Following is a list of some of the actions
and functions of progesterone. More information and references can be found
in the book What's Your
Menopause Type? |
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The
Menstrual Cycle and the Endometrium |
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Progesterone prevents development of endometrial cancer 1.
Low progesterone with unopposed estrogen
may be one cause of dysfunctional uterine bleeding 2. Progesterone
may help decrease uterine contractions, cramping and pain 3, 4. The
Vagina & Urinary Tract Excessive progesterone may increase urinary incontinence
and even counteract the beneficial effects of estrogen in maintaining urinary
control 5, 6, 7, 8. The
Libido Excessive progesterone may decrease libido due to
antiestrogen and anti-androgen effect 9, 10. As well as decreasing
libido, excessive levels may induce depression 11. Blood
Sugar & Insulin While estrogens help the cells of the body utilize glucose
more efficiently by making them more sensitive to insulin, progesterone can
cause a decrease in insulin sensitivity, having an effect on blood sugar that
is similar glucocorticosteroids 12. This interference with the
action of insulin can interfere with normal glucose uptake and cause insulin
resistance 13, 14, 15, 16, 17. The ability of progesterone to interfere with proper
function of insulin and glucose has since been associated with gestational
diabetes 18, 19, 20 as well as hormone replacement therapies 21,15,
22, 12 and has been been observed in both synthetic & non-synthetic
progesterone 20, 23, 24, 12. Even the high progesterone levels
which occur naturally during the luteal phase can induce insulin resistance
in some women 21, 16. The
Brain – Mood & Memory Progesterone and its metabolites result in increased
relaxation and reduced anxiety in a way that is similar to the effects of
benzodiazepines 25, 26 by a direct effect on neurotransmitter
receptors called Gamma-AminoButyric Acid type A (GABAA) receptors 27.
When progesterone levels drop a woman can experience withdrawals similar to
the withdrawal seen with benzodiazepine, barbiturate, and alcohol withdrawal 29.
Excessive levels may cause decreased coordination, slowed
reflexes, depression and impaired memory and reasoning skills 30, 31,
32, 33, 34. The sedating effects of excessive progesterone can cause
drowsiness and even induce sleep 35, 32, 36. The nerve calming
effect of progesterone is so pronounced that both natural progesterone and
medroxyprogesterone have both been shown to decrease seizures in women with
epilepsy 37, 38. Progesterone has a protective, stimulating effect on
breathing patterns during sleep, resulting in decreased incidence of sleep
apnea, a serious condition in which the body is deprived of oxygen 39,
40, 41, 42. The action of progesterone on GABAA receptors have been associated
with an increase appetite and food intake 43, 44, 45. The
Breasts Progesterone insufficiency may play a role in the
development of breast cancer 46, however progesterone may also
play a role in the proliferation of some progesterone receptor forms of
breast cancer 47. This increased risk is associated with the
increased production of IGF-1 by breast cells stimulated by excessive
progesterone 48, 49 - resulting in the proliferation of several forms
of breast cancer cells 50. The
Skin Though progesterone does not increase skin thickness 51,
it does increase blood flow to the skin 52 resulting in an
increased ability to sweat and loose the extra heat through the skin 53.
Progesterone can also raise body temperature, enhancing the ability to
tolerate cold 53. Bones
& Osteoporosis Progesterone has stimulating effect on the bone building
osteoblasts resulting in increased bone building activity 54, 55, 56,
57, 58, 59, 60. This is due to a direct stimulation of the progesterone
receptors in osteoblast bone cells 61, 62, as well as an increased
secretion of IGF-1 and other growth factors by the bone cells exposed to
porgesterone 63, 64, 65. The most positive effect is seen when
estrogen & progesterone are used in combination 66. The
Heart Natural micronized progesterone may cause a significant
lowering of in blood pressure in postmenopausal women with mildly to
moderately high blood pressure 67, possibly due to the
vasodilating effect of action of progesterone 68. Natural micronized progesterone will not reduce the good
HDL levels that are enhanced by estrogen replacement 69, and will
result in higher HDL than when synthetic progestogens are used 70.
This lipoprotein (a) benefit of estrogen is not diminished
by either synthetic (medroxyprogesterone acetate) or natural micronized
progesterone 71, 72. References: (1) Mauvais-Jarvis P, Kuttenn F. [Is progesterone insufficiency
carcihogenic]? [Article in French] Nouv Presse Med 1975 Feb 1;4(5):323-326 (2) Gorodeski IG,
Geier A, Siegal A, Beery R, Lunenfield B, Langzam J, Bahari CM. Decreased
Ratio of TotalProgesteroen to Total Estradiol Receptor Levels in Endometria
of Women with Adult Dysfunctional Uterine Bleeding. Gynecol. Obstet. Invest.
22:22-28 (1986) (3) Putnam CD, Brann DW, Kolbeck RC, Mahesh VB. Inhibition of
uterine contractility by progesterone and progesterone metabolites: mediation
by progesterone and gamma amino butyric acidA receptor systems. Biol Reprod
1991 Aug;45(2):266-272 (4) Cabral R, Gutierrez M, Fernandez AI, Cantabrana B,
Hidalgo A. Progesterone and pregnanolone derivatives relaxing effect on
smooth muscle. Gen Pharmacol 1994 Jan;25(1):173-178 (5) Batra SC, Iosif CS. Progesterone receptors in the female
lower urinary tract. J Urol 1987 Nov;138(5):1301-4 (6) Caissel J, Ghaddar
Y. [Urodynamic study of urinary incontinence appearing in the fifth month of
pregnancy and persisting after delivery. The role of progesterone].[Article
in French] Ann Urol (Paris) 1984 Sep;18(5):356-60 (7) Rud T. The effects
of estrogens and gestagens on the urethral pressure profile in urinary
continent and stress incontinent women. Acta Obstet Gynecol Scand
1980;59(3):265-70 (8) Miodrag A,
Castleden CM, Vallance TR. Sex hormones and the female urinary tract. Drugs
1988 Oct;36(4):491-504 (9) Mauvais-Jarvis P, Kuttenn F. [Is progesterone insufficiency
carcihogenic]? [Article in French] Nouv Presse Med 1975 Feb 1;4(5):323-326 (10) Amadeo M. Antiandrogen treatment of
aggressivity in men suffering from dementia. J Geriatr Psychiatry Neurol 1996
Jul;9(3):142-5 (11) Glick ID, Bennett
SE. Psychiatric complications of progesterone and oral contraceptives. J Clin
Psychopharmacol 1981 Nov;1(6):350-367 (12) Lindheim SR, Presser SC, Ditkoff EC,
Vijod MA, Stanczyk FZ, Lobo RA. A possible bimodal effect of estrogen on
insulin sensitivity in postmenopausal women and the attenuating effect of
added progestin. Fertil Steril 1993 Oct;60(4):664-7 (13) Sutter-Dub MT, Dazey B. [Role of
progesterone in the insulin-resistance during pregnancy in the rat].[Article
in French] Ann Endocrinol (Paris) 1979 Jan-Feb;40(1):37-8 (14) Sutter-Dub MT. Effects of pregnancy
and progesterone and/or oestradiol on the insulin secretion and pancreatic
insulin content in the perfused rat pancreas. Diabete Metab 1979
Mar;5(1):47-56 (15) Elkind -Hirsch KE, Sherman LD,
Malinak R. Hormone replacement therapy alters insulin sensitivity in young
women with premature ovarian failure. J Clin Endocrinol Metab 1993
Feb;76(2):472-5 (16) Tsibris JC, Raynor LO, Buhi WC,
Buggie J, Spellacy WN. Insulin receptors in circulating erythrocytes and
monocytes from women on oral contraceptives or pregnant women near term. J
Clin Endocrinol Metab 1980 Oct;51(4):711-7 (17) Leturque A, Satabin P, Ferre P,
Girard J. [Insulin resistance during pregnancy]. [Article
in French] Ann Endocrinol (Paris) 1980 Nov-Dec;41(6):573-8 (18) Ri K. [Study on insulin resistance
in rats treated with estrogen and progesterone--assessment with the
euglycemic glucose clamp technic].[Article in Japanese] Nippon Naibunpi
Gakkai Zasshi 1987 Jun 20;63(6):798-808 (19) Sutter-Dub MT, Dazey B, Vergnaud MT,
Madec AM. Progesterone and insulin-resistance in the pregnant rat. I. In vivo
and in vitro studies. Diabete Metab 1981 Jun;7(2):97-104 (20) Sutter-Dub MT, Vergnaud MT.
Progesterone and insulin resistance. III. Time-course study of progesterone
action on differentially labelled 14C-glucose utilization by adipose tissue
and isolated adipocytes of the female rat. J Physiol (Paris) 1981
Sep;77(6-7):797-802 (21) Puah JA, Bailey CJ. Effect of
ovarian hormones on glucose metabolism in mouse soleus muscle.
Endocrinology 1985 Oct;117(4):1336-40 (22) Colacurci N, Zarcone R, Mollo A,
Russo G, Passaro M, de Seta L, de Franciscis P. Effects of hormone
replacement therapy on glucose metabolism. Panminerva Med 1998
Mar;40(1):18-21 (23)
Colacurci N, Zarcone R, Mollo A, Russo G, Passaro M, de Seta L, de
Franciscis P. Effects of hormone replacement therapy on glucose metabolism.
Panminerva Med 1998 Mar;40(1):18-21 (24)
Kumagai S, Holmang A, Bjorntorp P. The effects of oestrogen and
progesterone on insulin sensitivity in female rats. Acta Physiol Scand
1993 Sep;149(1):91-7 (25) Lancel M, Faulhaber J, Holsboer F,
Rupprecht R. Progesterone induces changes in sleep comparable to those of
agonistic GABAA receptor modulators. Am J Physiol 1996 Oct;271(4 Pt
1):E763-E772 (26 Putnam CD, Brann DW, Kolbeck RC,
Mahesh VB. Inhibition of uterine contractility by progesterone and
progesterone metabolites: mediation by progesterone and gamma amino butyric
acidA receptor systems. Biol Reprod 1991 Aug;45(2):266-272 (27) Backstrom T. Symptoms related to the
menopause and sex steroid treatments. Ciba Found Symp 1995;191:171-180 (29) Smith SS, Gong QH, Li X, Moran MH,
Bitran D, Frye CA, Hsu FC. Withdrawal from 3alpha-OH-5alpha-pregnan-20-One
using a pseudopregnancy model alters the kinetics of hippocampal GABAA-gated
current and increases the GABAA receptor alpha4 subunit in association with
increased anxiety. J Neurosci 1998 Jul 15;18(14):5275-84 (30) Freeman EW, Purdy RH, Coutifaris C,
Rickels K, Paul SM. Anxiolytic metabolites of progesterone: correlation with
mood and performance measures following oral progesterone administration to
healthy female volunteers. Neuroendocrinology 1993 Oct;58(4):478-484 (31) Rice MM, Graves AB, McCurry SM,
Larson EB. Estrogen replacement therapy and cognitive function in
postmenopausal women without dementia. Am J Med 1997 Sep 22;103(3A):26S-35S (32) Freeman EW, Weinstock L, Rickels K,
Sondheimer SJ, Coutifaris C. A placebo-controlled study of effects of oral
progesterone on performance and mood.
Br J Clin Pharmacol 1992 Mar;33(3):293-298 (33) Korneyev A, Costa E. Allopregnanolone
(THP) mediates anesthetic effects of progesterone in rat brain. Horm Behav
1996 Mar;30(1):37-43 (34) Glick ID, Bennett SE. Psychiatric
complications of progesterone and oral contraceptives. J Clin Psychopharmacol
1981 Nov;1(6):350-367 (35)
Arafat ES, Hargrove JT, Maxson WS, Desiderio DM, Wentz AC, Andersen
RN. Sedative and hypnotic effects of oral administration of micronized
progesterone may be mediated through its metabolites. Am J Obstet Gynecol
1988 Nov;159(5):1203-1209 (36) de Wit H, Rukstalis M. Acute effects
of triazolam in women: relationships with progesterone, estradiol and
allopregnanolone. Psychopharmacology (Berl) 1997 Mar;130(1):69-78 (37) Herzog AG. Reproductive endocrine
considerations and hormonal therapy for women with epilepsy. Epilepsia
1991;32 Suppl 6:S27-33 (38)
Galli R, Michelini S, Bartalena L, Massetani R, Pani L, Grasso L,
Cassano GB, Martino E, Purdy RH, Murri L. Circulating levels of
anticonvulsant metabolites of progesterone in women with partial epilepsy in
the intercritical phase. Ital J Neurol Sci 1996 Aug;17(4):277-281. (39) Block AJ, Wynne JW, Boysen PG.
Sleep-disordered breathing and nocturnal oxygen desaturation
in postmenopausal women. Am J Med 1980 Jul;69(1):75-79 (40)
Bayliss DA, Millhorn DE, Gallman EA, Cidlowski JA. Progesterone
stimulates respiration through a central nervous system steroid
receptor-mediated mechanism in cat. Proc Natl Acad Sci U S A 1987
Nov;84(21):7788-92 (41)
Pickett CK, Regensteiner JG, Woodard WD, Hagerman DD, Weil JV, Moore
LG. Progestin and estrogen reduce sleep-disordered breathing in
postmenopausal women. J Appl Physiol 1989 Apr;66(4):1656-61 (42)
Bayliss DA, Cidlowski JA, Millhorn DE. The stimulation of respiration
by progesterone in ovariectomized cat is mediated by an estrogen-dependent
hypothalamic mechanism requiring gene expression. Endocrinology 1990
Jan;126(1):519-27 (43)
Fieldstone A, Zipf WB, Sarter MF, Berntson GG. Food intake in
Prader-Willi syndrome and controls with obesity after administration of a
benzodiazepine receptor agonist. Obes Res 1998 Jan;6(1):29-33 (44)
Lett BT, Grant VL, Neville LL, Davis MJ, Koh MT Chlordiazepoxide
counteracts activity-induced suppression of eating in rats. Exp Clin Psychopharmacol 1997 Feb;5(1):24-7 (45)
Chen SW, Rodriguez L, Davies MF, Loew GH. The hyperphagic effect of 3
alpha-hydroxylated pregnane steroids in male rats. Pharmacol Biochem Behav
1996 Apr;53(4):777-782 (46) Mauvais-Jarvis P, Kuttenn F. [Is progesterone insufficiency
carcihogenic]? [Article in French] Nouv Presse Med 1975 Feb 1;4(5):323-326 (47) Umekita Y, Yoshida H.
Immunohistochemical study of hormone receptor and hormone-regulated protein
expression in phyllodes tumour: comparison with fibroadenoma. Virchows Arch
1998 Oct;433(4):311-4 (48) Elizalde PV, Balana ME, Charreau EH.
[Growth hormones and oncogenes in mammary adenocarcinomas induced by
medroxyprogesterone acetate in BALB/c mice].[Article in Spanish] Medicina (B
Aires) 1997;57 Suppl 2:70-4 (49) Clayton SJ, May FE, Westley BR. Insulin-like
growth factors control the regulation of oestrogen and progesterone receptor
expression by oestrogens. Mol Cell Endocrinol 1997 Apr 4;128(1-2):57-68 (50)
Bentel JM, Lebwohl DE, Cullen KJ, Rubin MS, Rosen N, Mendelsohn J,
Miller WH Jr. Insulin-like growth factors modulate the growth inhibitory
effects of retinoic acid on MCF-7 breast cancer cells J Cell Physiol 1995
Oct;165(1):212-21. (51) Eisenbeiss C, Welzel J, Schmeller W.
The influence of female sex hormones on skin thickness: evaluation using 20
MHz sonography. Br J Dermatol 1998 Sep;139(3):462-467 (52)
Harvell J, Hussona-Saeed I, Maibach HI. Changes in transepidermal
water loss and cutaneous blood flow during the menstrual cycle. Contact
Dermatitis 1992 Nov;27(5):294-301 (53)
Hessemer V, Bruck K. Influence of menstrual cycle on shivering, skin
blood flow, and sweating responses measured at night. J Appl Physiol 1985
Dec;59(6):1902-10 (54)
Chen L. Induction of osteocalcin gene expression in vitro by
progesterone. J Tongji Med Univ 1997;17(2):72-74 (55)
MacNamara P, Loughrey HC. Progesterone receptor A and B isoform
expression in human osteoblasts. Calcif Tissue Int 1998 Jul;63(1):39-46 (56)
Chen L, Foged NT. Differentiation of osteoblast in vitro is regulated
by progesterone. J Tongji Med Univ 1996;16(2):83-86 (57)
MacNamara P, O'Shaughnessy C, Manduca P, Loughrey HC. Progesterone
receptors are expressed in human osteoblast-like cell lines and in primary
human osteoblast cultures. Calcif Tissue Int 1995 Dec;57(6):436-441 (58) Heersche JN, Bellows CG, Ishida Y.
The decrease in bone mass associated with aging and menopause. J Prosthet
Dent 1998 Jan;79(1):14-16 (59) Verhaar HJ, Damen CA, Duursma SA,
Scheven BA. A comparison of the action of progestins and estrogen on the
growth and differentiation of normal adult human osteoblast-like cells in
vitro. Bone 1994 May;15(3):307-311 (60) Tremollieres F, Pouilles JM, Ribot
C. [Postmenopausal bone loss. Role of progesterone and androgens].[Article in
French] Presse Med 1992 Jun 6;21(21):989-993 (61) Wei LL, Leach MW, Miner RS, Demers
LM. Evidence for progesterone receptors in human osteoblast-like cells.
Biochem Biophys Res Commun 1993 Sep 15;195(2):525-532 (62) Pensler JM, Langman CB, Radosevich
JA, Maminta ML, Mangkornkanok M, Higbee R, Molteni A. Sex steroid hormone
receptors in normal and dysplastic bone disorders in children. J Bone Miner
Res 1990 May;5(5):493-498 (63) Tremollieres FA, Strong DD, Baylink
DJ, Mohan S. Progesterone and promegestone stimulate human bone cell
proliferation and insulin-like growth factor-2 production. Acta Endocrinol
-Copenh 1992 Apr;126(4):329-337 (64) Ribot C, Tremollieres F. [Sex
steroids and bone tissue].[Article in French] Ann Endocrinol (Paris)
1995;56(1):49-55 (65) Barengolts EI, Kouznetsova T, Segalene
A, Lathon P, Odvina C, Kukreja SC, Unterman TG. Effects of progesterone on
serum levels of IGF-1 and on femur IGF-1 mRNA in ovariectomized rats. J Bone
Miner Res 1996 Oct;11(10):1406-1412 (66) Slootweg MC, Ederveen AG, Schot LP,
Schoonen WG, Kloosterboer HJ. Oestrogen and progestogen synergistically
stimulate human and rat osteoblast proliferation. J Endocrinol 1992
May;133(2):R5-R8 (67) Rylance PB, Brincat M, Lafferty K,
De Trafford JC, Brincat S, Parsons V, Studd JW. Natural progesterone and
antihypertensive action. Br Med J (Clin Res Ed) 1985 Jan 5;290(6461):13-14 (68) Radwanska E. The role of
reproductive hormones in vascular disease and hypertension. Steroids 1993
Dec;58(12):605-10 (69) Ottosson UB, Johansson BG, von
Schoultz B. Subfractions of high-density lipoprotein cholesterol during
estrogen replacement therapy: a comparison between progestogens and natural
progesterone. Am J Obstet Gynecol 1985 Mar 15;151(6):746-50 (70) Chen FP, Lee N, Soong YK. Changes in
the lipoprotein profile in postmenopausal women receiving hormone replacement
therapy. Effects of natural and synthetic progesterone. J Reprod Med 1998
Jul;43(7):568-74 (71) Kim CJ, Jang HC, Cho DH, Min YK.
Effects of hormone replacement therapy on lipoprotein(a) and lipids in
postmenopausal women. Arterioscler Thromb 1994 Feb;14(2):275-81 (72) Espeland MA, Marcovina SM, Miller V,
Wood PD, Wasilauskas C, Sherwin R, Schrott H, Bush TL. Effect of
postmenopausal hormone therapy on lipoprotein(a) concentration. PEPI
Investigators. Postmenopausal Estrogen/Progestin Interventions. Circulation
1998 Mar 17;97(10):979-86 |
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