You may have read that many women find relief in the insulin sensitizing/anti-diabetic drugs for PCO. The 3 that are generally used are called Metformin (Glucophage), Avandia (Rosiglitazone), and Actos (Pioglitazone) . Metformin is the most widely prescribed and the most well studied in medical literature. Avandia and Actos are part of a newer drug class and have a different way of acting in the body than what metformin has. If you are having trouble getting your doctor to prescribe these things, I have some references that you can either give them him/her or ask them to review them and see if you can get it prescribed then. There is a previous drug called Rezulin in the same class as Avandia and Actos. It was removed from the market due to toxic liver problems.
A brand new type of drug that is in the works right now is called d-chiro-inositol. Its a natural substance that appears to have great success in limited trials, specifically for PCO treatment.
General prescribing methods have been 1 pill with dinner (500 mg) for one week. The next week you had another 500 mg pill for breakfast. The third week you had a pill with lunch, for a total of 1500 mg. This appears to be the minimum dosage that most women have success with. Some doctors do take it up to 2250 mg a day, as their experience has been that 2000 mg is the minimum dosage. What are the side effects of Metformin?
Most women complain about diarreah, stomach pains, nausea, metal tastes in the mouth. These affects generally last less than 3 weeks. They also tend to reoccur once you go up on the dosage. Taking it after the first few bites of meal or at the beginning of a meal tends to work pretty well. Some women have complained about the low carbing and metformin together at first are a problem. If you are looking at getting pregnant, some miscarriages have been reported, due to clotting factors. This is when metformin is combined with baby aspirin. This isn't official, just something that has been noticed. However, metformin alone during pregnancy has not yet produced a problem.
There is a life threatening side effect of metformin called lactic acidosis. It is so rare that only about 1 in 30,000 to 60,000 people get this problem. Basically, as long as you eat and drink normally (don't starve yourself), make sure that you alert your doctor before taking any other medications with it or doing any medical procedures with it, you won't have a problem. However, check out these 3 articles on it, so that you know what the symptoms of it are:
Metformin reactions and Lactic Acidosis
In addition, it may have other problem effects: Is metformin going to help me lose weight?
Maybe. There are women who have lost weight on it due to simply the drug itself. There are others who had to combine low carbohydrate dieting and exercise with it to get this effect. Then you have others who didn't lose weight on it. It is not a weight loss drug per se, so don't be surprised if you don't lose anything on it. Can I have alcohol on metformin/glucophage?
Depends, different people have had different reactions. Some ladies said they couldn't manage any alcohol, others had no problems. Is there anything that metformin doesn't work for?
Hair loss (scalp) and hair growth (hirsuitism) seem to slow down, but do not stop. I believe the reason why this occurs is that once the hairs turn 'terminal' or the dark, large hairs that you see, you can't make it return back to its 'vellus' or soft, light, fine state.
Spironolactone or Aldactone is the drug of choice, in combination with a contraceptive (because it causes birth defects). It also helps with acne.
Flutamide (eulexin) is another hirsuitism drug. The side effects of diarreah, hypertension and liver problems can be a problem. Flutamide, in one study (missing from Medscape March 26, 2002) was superior to finasteride in how it worked. The Journal of Clinical Endocrinology and Metabolism Vol. 83 No. 1 pp. 99-102 has an article on "Hormonal effects of flutamide in young women with polycystic ovary syndrome" and it seems that ovulation was restored in the anovulatory PCOS patients - the ages of the girls were 16 to 19. The Journal of Endocrinology Invest? Vol. 17 no. 3 pp. 195-9 had an article on "The use of flutamide in the management of hirsuitism and said that it helped.
Finasteride (proscar) is tolerated well, but gives liver and pregnancy problems. In the Gynecologic Endocrinology Vol. 11. no 4 pp. 251-7 article "Treatment of hirsutism by finasteride and flutamide in women with polycystic ovary syndrome" the opposite was found: finasteride worked better than flutamide.
Bicalutamide (casodex) has the fewest side effects of any drug in this class, but like most of the others, can cause liver damage.
Nilutamide (nilandron) can cause night blindness, nausea, digestive problems and liver problems, so it usually isn't prescribed at all. Believe it or not, Cimetidine (tagamet) sometimes works on hirsuitism, but not really well enough.
Just as a side note, the progesterone component of the European birth control pill Diane-35, called Cyproterone, works really well. If you are in Europe and need a birth control pill, this one gets high marks from doctors and patients alike. In the Gynecologic Endocrinology Vol. 10 no. 4 pp. 249-55 article "Comparison of four different treatment regimes in hirsutism related to polycystic ovary syndrome" ketoconazole was the best, followed by cyproterone (Diane 35 progesterone component), OC's and then spironolactone. Beware of the effects that ketoconazole has on your lipoproteins.
A quick list is on Ruth's page or SpringNet.
The first drug of choice is Lupron. In addition to well known side effects (pain, dizzyness, bone loss, hot flashes), hypertension/high blood pressure has been acknowledged by the TAP Pharmaceuticals Comp. as being a possible side effect. Because Lupron is an IM or intermusucular administered drug and painful, there is a drug that is given SQ or subcutaneously (under the skin) called ZOLADEX or GOSERELIN that you might want to check into. If you can't stand shots, there is a nasal spray called SYNAREL or Nafarelin that you can use. It is used twice a day, but if you have allergies or nasal problems, it can be rough on them.
Please note that some doctors will use what is known as 'add back' therapy. This is giving you small amounts of estrogen and/or progesterone (lots of times as HRT) to help ease the problems of these drugs, and to make the side effects not so bad. Fosamax is a drug that helps slow down or halt the bone loss you get, but Actonel seems to be a better choice, as it doesn't have the restraints on it that Fosamax does. Intermittent use of thyroid hormone may help bone loss also.
The gonadorelin analogs are longer acting versions of the GnRH agonists, which is what the class of drugs Lupron is in. These would be Buserelin or Suprefact and Leuprorelin (Prostrap). Another drug in this type is called histrelin.
Another class of drugs appears to have some promise for endometriosis. These are anti-progesterones. Mifepristone is the best known and possibly the only one of these. It is not approved in all countries. It has great promise for other types of problems, but because it is combined with another drug to become an abortifacient, is controversial. Dr. Speroff does mention it in his book on page 858, that it may be worth using, but without more clinical data from the US, there is little to be done on it.
Deslorelin is a nasal spray that can improve mammogram readings in women, but it may have uses for endometriosis sufferers also.
Dimetriose is an Australian drug that appears to be Danazol like and is used for the treatment of endometriosis. There is an E-zine on it.
One of the newer GnRH antagonists to come out is called Ganirelix (Antagon). A similar drug in this class is called Cetrorelix. The really nice thing about this class of drugs is that there is no or little flare effect. What happens with Lupron is that in the first couple of weeks or so, your hormones don't get supressed, they surge. This creates a lot of problems, especially where pain and other symptoms get worse. This group of drugs don't seem to have that problem.
Provera is a synthetic hormone that comes in two forms, tablets to make you have a period, and a Depo-Provera contraceptive shot.
Provera tablets are the ones you will see most often. You should get your period anywhere from 10 to 13 days after taking the last pill. The Physicians Desk Reference has cholostatic jaundice as an adverse reaction, and those with liver disfunction shouldn't take it.
As for the shot, be sure about what you want to do for more children before taking this drug. Any side effects may be helped by a ten day course of ethinyl estradiol 0.05mg or some estrogen replacement. A poll of women who had taken the shot reported that NO information at all was given to them about it. For example, they weren't told that 6 to 22 months is how long it takes to get your cycles back and get pregnant after finishing using this drug. One lady has never ovulated since taking this shot. One lady is going after the makers for the damage Depo Provera has caused for her. Something else you want to look out for is the number of women who have reported depression on this drug. As for long term side effects of depo provera, it would be worth checking them out.
Prometrium is a 'Provera like' natural progesterone that helps you to have a period. It is highly preferred by many women, due to the fact that side effects (hot flashes, moodiness, etc.) are not as bad as what they are on Provera tablets. The kicker is that if you take enough of it in pill form, it puts you to sleep. The only way to get rid of that is to take it vaginally.
Clomid is normally taken from days 3 to 7 or days 5 to 9 of your cycle to bring on ovulation. This should only be used for 3 to 4 cycles, especially if you are not ovulating. The starting dosage is 50 mg, going up 50 mg each time if you are not pregnant or not ovulating, to 200 mg. Clomid does have a reputation of causing ovarian cysts, something which should be monitored. Also, after several months in a row, Clomid causes the cervical fluid to become very thick, and therefore impedes the sperm going through the vagina and uterus. Actually, Clomid was first tested as a contraceptive, but it was found that in the first few months, it helped you to become pregnant. After that, it acted as a contraceptive type. A lot of ob/gyn's do tend to keep you on this drug for longer than recommended, so that is something to watch out for. INCIID, one of the well known authorities on reproductive issues, has an article called, "Clomid Use and Abuse" which I recommend highly. Clomid doesn't increase pregnancy rates if you are using IUI or interuterine insemination. I just checked out the November 2000 (Vol 74 No 4 p 749) Fertility and Sterility and in there, the overall pregnancy rate with Clomid runs about 30 to 40%.
Tamoxifen, a breast cancer drug, is used in Europe instead of Clomid. Its starting dose is 10 mg daily from days 2 to 6 of your cycle. You don't want to go above 40mg, and use it less than 9 to 12 months. After that, it doesn't appear to work.
Guaifenesin (dexamethosone) is the ingredient in tussin brands cough syrup. Taken 1 to 2 teaspoons a day for 3 to 4 days before you ovulate, it tends to make the cervical mucus thinner, thereby making it easier for the sperm to go through the reproductive tract. At the same time, it inhibits adrenal androgen function, which may have some uses for PCO women.
These are drugs that are given to you after Clomid has failed to help you get pregnant. Briefly: Dr. Speroffs page and Fertiliext have more indepth information about these drugs. Here is a short run down:
Pergonal, Humegon, and Repronex are combination FSH/LH drugs
Metrodin is pure FSH and is an IM or intermuscular injection. Fertinex and Metrodin HP are subcutaneous injections. Gonal-F, Follitism, and Puregon are recombinant FSH drugs. Follitism is not prefered over Gonal-F because it is diluted with saline versus sterile water. It might be worth asking your doctor if you can change to Gonal-F, or use sterile water to dilute it with. To make you ovulate you will be given a shot of 10,000 units of HCG, or Profasi/Pregnyl. There is a prescription cream called EMLA which helps with the sting of these shots.
Have questions on taking drugs in pregnancy or during breastfeeding? Check out this site. Also see: Drugs in Pregnancy (A to D)
I would review Personal MD's sites on drugs and congenital risks have good information that is too much to review here.
The Rxassist home page might be able to help. Ask for generic medications instead of brand. If you are looking for birth control pills, try seeing if you can use a cheaper brand or if you can get them from Planned Parenthood or any of the local clinics.
Drug Library Online
Medicine from International Pharmacies - Foreign and Overseas Drug Sources
WebRx Pharmacy Palace
Drug Information Database
RxNorth.com - Mediplan Prescription Plus Pharmacy
BMJ -- Hopkinson et al. 317 (7154): 0
Kidson, Polycystic ovary syndrome: a new direction in treatment
POLYCYSTIC OVARY SYNDROME
Welcome to the U. of Chicago's Center for PCOS
Metformin treatment of anovulation and infertility associated with PCOS
Menstrual disorders by Dr. Andrea Dunaif
Fertility: An Insulin Resistance Problem?
Treatment of Polycystic Ovary Syndrome with Insulin Lowering Medications
Metformin - New Therapy for PCOS.
Metformin: a review of its metabolic effects
Original Articles -- NEJM 1999; 340: 1314-1320
Effect of Metformin in Pediatric Patients With Type 2 Diabetes
American Society for Reproductive Medicine, April 2000, Use of Insulin Sensitizing Agents in the Treatment of Polycystic Ovary Syndrome. See the ASRM for a copy of this report.
Diabetes Care 1993 Oct;16(10):1387-90 "Metformin improves glucose, lipid metabolism, and reduces blood pressure in hypertensive, obese women."
Dr. Leon Speroff, "Clinical Gynecologic Endocrinology and Infertility" Lippincott, Williams & Wilkins; ISBN: 0683078992, Pg 533 recommends metformin for those women with hyperinsulinemia and hyperandrogenism.
European Journal of Endocrinology Vol. 138 no. 3 pp. 269-74 "Therapeutic effects of metformin on insulin resistance and hyperandrogenism in PCOS."
Fertility and Sterility Vol 72, No 6, December 1999, La Marca A, Morgante G, Paglia T, Ciota L, Cianci A, and De Leo V, Effects of metformin on adrenal steroidogenesis in women with polycystic ovary syndrome. A reduction in free T, SHBG, 17-hydroxyprogesterone, T, and androstenedione to ACTH.
Fertility and Sterility 1998 Apr;69(4):691-6 Metformin therapy improves the menstrual pattern with minimal endocrine and metabolic effects in women with PCOS."
Metabolism 1994 May;43(5):647-54 "Metformin therapy in PCOS reduces hyperinsulinemia, IR, hyperandrogenemia, and systolic blood pressure, while facilitating normal menses and pregnancy."
Effects of Metformin on Spontaneous and Clomiphene-Induced Ovulation in the Polycystic Ovary Syndrome by Nestler JE et all in the New England Journal of Medicine June 25, 1998, Volume 338, Number 26.
Metabolism 1997 Apr;46(4):454-7 "Metformin therapy is associated with a decrease in plasma plasminogen activator inhibitor-1, lipoprotein(a), and immunoreactive insulin levels in patients with the PCOS."
N Engl J Med 1998;338:1876-1880, "Metformin improves ovulation in obese women with polycystic ovary syndrome, June 25th issue of The New England Journal of Medicine". Dr. John E. Nestler.
New England Journal of Medicine 1996 Aug 29;335(9):617-23 "Decreases in ovarian cytochrome P450c17 alpha activity and serum free testosterone after reduction of insulin secretion in PCOS."
Obstetrics and Gynecology 1997;90:392-5, Velazquez E, Acosta A, Mendoza SG, Menstrual cyclicity after metformin therapy in polycystic ovary syndrome.
Review of Medicine in Chili (Spanish) 1997 Dec;125(12):1457-63 "Effects of metformin on insulin resistance in obese and hyperandrogenic women."
Menstrual cyclicity after metformin therapy in polycystic ovary syndrome by Velazquez E, Obstetrics and Gynecology 1997 Sep;90(3):392-5
Pioglitazone and metformin reverse insulin resistance induced by tumor necrosis factor-alpha in liver cells by Solomon SS et all, Horm Metabolism Res 1997 Aug;29(8):379-82
Metformin enhances clearance of chylomicrons and chylomicron remnants in nondiabetic mildly overweight glucose-intolerant subjects by Grosskopf I et all, Diabetes Care 1997 Oct;20(10):1598-602
Insulin regulation of human ovarian androgens by Nestler JE in Human Reproduction 1997 Oct;12 Suppl 1:53-62
Insulin resistance: current concepts by Bloomgarden ZT in Clinical Therapy 1998 Mar-Apr;20(2):216-32;discussion 215
New drugs against insulin resistance (Swedish) by Nilsson P et all in Lakartidningen 1998 Jun 10;95(24):2832-4
Insulin and Polycystic Ovary Syndrome: a new look at an old subject by Ciampelli M; Lanzone A in Gynecological Endocrinology 1998 Aug;12(4):277-92 Prescribe met
Understanding the underlying metabolic abnormalities of polycystic ovary syndrome and their implications by Taylor AE in American Journal of Obstetrics and Gynecology 1998 Dec;179(6 Pt 2):S94-100 Important health risk factors
Doctor to Doctor: Hyperinsulinism: The metabolic trap in resistant obesity at http://commodore.perry.pps.pgh.pa.us/~odonnell/ezrin.html
Cardiovascular risk continuum: implications of insulin resistance and diabetes by Hsueh WA and Law RE in the American Journal of Medicine, 1998 Jul 6;105(1A):4S-14S
Insulin resistance. Receptor and post-receptor abnormalities (Italian) by Liguori M et all, Minerva Endocrinology 1998 Jun;23(2):37-52
Lean women with polycystic ovary syndrome respond to insulin reduction with decreases in ovarian P450c17 alpha activity and serum androgens by Jestler JE and Jakubowicz DJ in the Journal of Clinical Endocrinology and Metabolism 1997 Dec;82(12):4075-9
Use of metformin in the management of adolescents with polycystic ovary syndrome (Spanish) by Zarate A et all, in Ginecol Obstet Mex 1997 Dec;65:504-7
Weight control and its beneficial effect on fertility in women with obesity and polycystic ovary syndrome by Pasquali R, in Human Reproduction 1997 Oct;12 Suppl 1:82-7 (covers administration (long and short term) of metformin)
Perspective in the treatment of insulin resistance by Scheen AJ in Human Reproduction 1997 Oct;12 Suppl 1:63-71
Effect of troglitazone on endocrine and ovulatory performance in women with insulin resistance-related polycystic ovary syndrome by Isao Hasegawa et all in Fertility and Sterility Vol 71, No 2, Feb 1999
Clinical Endocrinology (Oxford) 21:1440-1445, Ferriman D, Gallwey J, 1961 Clinical assessment of body hair growth in women.
Gynecologic Endocrinology Vol 10 no 4 pp 249-55 "Comparison of 4 different treatment regimes in hirsuitism related to PCOS."
Journal of Endocrinology Investment Vol 17 no 3 p 195-9 "The use of flutamide in the management of hirsuitism."
Gynecological Endocrinology Vol 11 no 4 pp 251-7 "Treatment of hirsuitism by finasteride and flutamide in women with PCOS."
Journal of Clinical Endocrinology and Metabolism Vol 83 no 1 pp 99-102 "Hormonal effects of fluatmide in young women with PCOS."
MEDLINEplus BUSERELIN (Systemic)
BCCA CDM Patient Information
Understanding Buserelin Information on Buserelin (Suprefact), uses and side effects.
MEDLINEplus HISTRELIN (Systemic)
FDA approves drug
FDA Approves Antagon For Women Undergoing Fertility Treatment
Treatment: Drugs - Infertility Net Links
BabyCenter | Fertility Drugs for Women
BioMed Holding - affordable fertility drugs
The Kentucky Center for Reproductive Medicine and IVF
Complete Infertility Guide to Tests, Drugs, and Procedures for Infertility
Dr. Derman's site
Determining Risk Between Depo-Provera Use And Increased Uterine Bleeding In Obese And Overweight Women
The Whole Truth About Contraception Bone density loss and Depo Provera Depo-Provera WebMD - Depo Provera Article WebMD - Another Depo Provera Article Depo Provera full list of interactions, etc. Depo Provera policy in Canada Why Must One 'Restart' a Method That Is Still Working? JAMA Contraception Information Center - Patient Education - Is Depo-Proveraź For You? Questions and Answers about birth control shots contraception BCCA CDM Monographs depo-provera.com Depo Provera Users' Information Resource Depo-Provera Injections Hormonal Methods November 1997 Drug Labeling Changes - Glucose Intolerance August 1998 Drug Labeling Changes Depo-Provera Abortion and Depo-Provera gp-uk archives - December 1997: Depot Provera
Women and Psychopharmacology
Bone density and Depo Provera
A nurses PDR about Depo Provera
OnHealth: Depo-Provera Planned Parenthood's Depo Provera info
Depot Medroxyprogesterone Acetate (Depo-Provera) -Royal Australian and New Zealand College of Obstetricians and Gynaecologists Physicians' Newsletter - 1998 Summer Issue Depo-Provera
depo2Depo Provera inserts Birth Control Information from McKinley - Depo Provera