Adverse Effects of BCPs Birth Control Pills

by Jeffrey Dach MD

Depression, Anxiety, Mood Disturbance and Other Adverse Effects of BCPs Birth Control Pills

The IUD is a Better Option.

Above left image: ParaGuard Copper T IUD  Intra-Uterine Device

Case Report: A 21 Year Old on OC’s (Oral Contraceptives)

Amy, a 21 year old college student came into the office with her mother because of depression, anxiety and severe mood disorder. Her other symptoms included forgetfulness, insomnia, and alternating euphoric and depressive states. Her medical history was unremarkable except for the past two years she had been on birth control pills (OC’s oral contraceptives). Her laboratory studies showed a severely low B12 level (217). The patient was advised to discontinue OC’s ( birth control pills), as the most likely cause of her symptoms. Six weeks later, after discontinuing the OC’s and taking B12 supplements, Amy reports all symptoms had resolved.

Switching to the Paraguard Copper T –  IUD

The IUD (Intra-Uterine Device) is actually a better option than the Oral Contraceptive, and Amy was switched over to the IUD, called the Paraguard  Copper T IUD, which is a plain IUD containing no hormones.    The Paraguard is safer and more effective than OC’s for women of all reproductive ages according to guidelines from the American College of Obstetrics and Gynecology. (44).  Amy was now a happy camper, as she no longer had the adverse effects and mood disturbances from “the Pill”, while she still had a safe and effective method of Birth Control in her IUD, the Paraguard Copper T.

What About the Mirena ?

Amy was advised to avoid the Mirena IUD because of the synthetic hormones impregnated into the Mirena.

Adverse Effects of OC’s Well Documented in Medical LIterature

The medical literature is full of reports of various nutritional deficiencies caused by oral contraceptives (OC’s) also called Birth Control Pills. Dr Brenda Herzberg reported that 25% of her patients stopped the OC’s because of headache, depression and loss of libido. She reported that 74% of patients found the IUD acceptable.(1)

Dr Melitis reported that OC’s are among many drugs that deplete the body of nutrients such as B6, B12 folate and Magnesium, and disturb Tryptophan metabolism which may cause depression. (2)

He says: “OCPs have been shown to increase the risk of cardiovascular events as well as breast, cervical, and liver cancer.”

OC’s (BCP’s) have been shown to deplete many nutrients. Specifically :

1) Vitamin B6 deficiency causes disruption in tryptophan metabolism.
2) Depletion of riboflavin (vitamin B2), folic acid, cobalamin (vitamin B12), ascorbic acid (vitamin C), and zinc.
3) Both B12 and Folate levels decrease by 40% with oral contraceptive use.
4) Lower folic-acid levels correlates with increased prevalence of abnormal Papanicolaou (Pap) smear results.
5) Increased coagulation leads to an increased risk of venous thrombosis and stroke

 

Here is a Summary Vitamin and Mineral Deficiencies Caused by Oral Contraceptives: (3)

 

1) birth control pills cause folic acid depletion with increased risk of cervical dysplasia and vascular thrombosis, Megaloblastic anemia, platelet hyperactivity and stroke: The authors recommend supplementation with folic acid at doses of 400-800 mcg per day, especially in women contemplating stopping the BCP’s to get pregnant. BCP induced Folate deficiency in the mother increases risk of neural tube defect in the embryo.

2) Oral contraceptives cause vitamin B6 depletion and depression, most likely associated with interference in the role that vitamin B6 plays in facilitating the tryptophan to niacinamide pathway. B6 deficiency and disruption of tryptophan may cause depression relieved by supplemental B6 (pyridoxine) tablets. Since pyridoxine in high doses can cause neurotoxicity, the P-5-P version is B6 is recommended. (4-7)

3) OC’s cause B12 deficiency – supplementation with B12 is recommended.

4) OC’s cause decreased Vitamin C levels- supplementation recommended.(3)

5) OC’s increase risk of venous thrombosis and stroke.

Oral contraceptives are to blame for deficiency in B6, and Tryptophan as well as deficiency in folate and B12 . These can cause mood disorders of depression, anxiety and even frank psychosis. (4-31) In addition to affecting the brain, B12 and folate deficiency can cause peripheral neuropathy, and megaloblastic anemia. (4-31) For women contemplating going off the “pill” and getting pregnant, folate deficiency increases risk of neural tube defect in the embryo, and folate supplementation is advised pre -conception (with 5-Methyl-Tetra- Folate preferably) to avoid birth defects.

Oral Birth Control Pills Increase Strokes and Heart Attacks

A 2005 metanalysis from Quebec summarized the risk associated with use of current low-dose Oral Contraceptives. They found the  risk for myocardial infarctions (heart attacks) and for ischemic strokes was doubled compared to non-users.  That’s a 200% increase !!

See the article: Bad News for the Nuva Ring

Also See the article: Why Transdermal Estrogen is Safer than Oral Estrogen

Testosterone and Binding Globulin (33-37)

Another disturbing finding is that OC (oral contraceptive) suppression of  ovarian production of testosterone which may reduce levels by 50-60 per cent, thus making OC’s useful as a treatment for acne.   Serum Binding Globulin is increased dramatically by OC’s  These effects on decreased testosterone and loss of libido may continue many years later after discontinuing the Oral contraceptive pills.(33-37)  The increased thyroid binding globulin can make thyroid test inaccurate, and cause artifacts in  thyroid lab parameters (33-37)

Why are OC’s Such a Problem?

One might ask, why are oral contraceptives so problematic.? The answer is that they contain synthetic, chemically altered hormones that are foreign to the human body. Any slight alteration in a hormone structure creates a “monster” which can wreck havoc on the fine tuned biochemistry of the human body. For an idea of how fine tuned this is, the difference between estrogen and testosterone is one hydrogen atom added to the chemical ring structure of the molecule. If a small a thing as one atom of hydrogen (the smallest atomic particle) can determine the sex on an individual whether male of female, then imagine the potential damage of the larger chemical alterations in the synthetic birth control pills.

The IUD is preferred over the oral contraceptive for college students(44-49)

If OC’s are no longer the preferred method of birth control, What Is? If we take away birth control pills, what are the remaining  birth control options for young college females who wish to avoid pregnancy?

ACOG News Release

As it turns out, a recent ACOG News Release  June 20, 2011 answers this question:

They say that IUDs (Intra-uterine Devices) : “are the most effective forms of reversible contraception available, and are safe for use by almost all reproductive-age women”.  

This statement comes Eve Espey, MD, MPH, who helped write a Practice Bulletin  by The American College of Obstetricians and Gynecologists (The College).   Dr Espy says , “The major advantage is that after insertion, IUD’s  work without having to do anything else. There’s no maintenance required.”

IUD is SAFE and Should Be First Line Method for Almost All Reproductive Ages (44)

Another earlier 2009 Committee Opinion released by ACOG (The College) says that IUDs (LARCs) should be offered as first-line contraceptive methods and encouraged as options for most women.

Features of the Paragard Copper T IUD:

1) Most effective method at preventing pregnancy
2) Most method cost effective when used long term
3) Does not impair fertility after removal
4) Can be used by women of all reproductive ages.
5) No Hormones in this Copper T IUD, and no increase in blood clots or stroke associated with BCP’s

Which IUD to Use?

Avoid the Mirena which has implanted synthetic hormones. Instead go with the Paraguard which has a proven track recod and has no added synthetic hormones.

Watch the Video on the Copper T IUD:

Who is Eve Espey MD ?

Dr. Espey chairs the ACOG working group for long-acting reversible contraceptives (IUD’s) and is a liaison member on the Committee for Underserved Women. She is a board member of the Society for Family Planning and for Physicians for Reproductive Choice and Health. Additionally, Dr. Espey is Associate Dean of Students at the University of New Mexico and has chaired the UNM School of Medicine Curriculum Committee, working to promote incorporation of reproductive health in the medical school curriculum.

Disclaimer: I have no financial relationship with any manufacturer of oral contraceptives or IUD’s.  Specifically I have no financial relationship with the makers of the ParaGard Copper T – IUD.

Update 2015: Vitamin_mineral_contraceptive_Dante_Obstet_Gynecol_2014
Dante, Giulia, Alberto Vaiarelli, and Fabio Facchinetti. “Vitamin and mineral needs during the oral contraceptive therapy: a systematic review.” International Journal of Reproduction, Contraception, Obstetrics and Gynecology 3.1 (2014): 1-10.

Westhoff, Carolyn L. et al., the Quick Start Study Group. “Oral Contraceptive Discontinuation: Do Side Effects Matter?” American journal of obstetrics and gynecology 196.4 (2007): 412.e1–412.e7. PMC. Web. 12 Jan. 2015.

This study shows women who report increased headache and moodiness during early months of OC use are more likely to discontinue. Subjects who gained weight  were also more likely to discontinue the OC by six months.

Articles With Related Content

The Safety Of Bio-Identical Hormones by Jeffrey Dach MD

Safety and Adverse Effects of Natural Progesterone

The Safety of Transdermal Estrogen Part One.

The Safety of Transdermal Estrogen Part Two.

Jeffrey Dach MD
7450 Griffin Road Suite 180
Davie, Fl 33314
954-972-4663
www.jeffreydach.com
www.drdach.com
www.naturalmedicine101.com
www.bioidenticalhormones101.com
www.truemedmd.com

Links and References

1) www.ncbi.nlm.nih.gov/pmc/articles/PMC1800460/ Br Med J. 1971 August 28; 3(5773): 495–500. Oral Contraceptives, Depression, and Libido Brenda N. Herzberg, Katharine C. Draper, Anthony L. Johnson, and Gillian C. Nicol Twenty-five per cent. stopped using oral- contraceptives because of side effects, the most common of which were headaches, depression, and loss of libido.The I.U.D. was acceptable to 74% of women, the only adverse affect being breakthrough bleeding. The improvement in mood and the increase in libido in the I.U.D. group suggest that this is a safe and acceptable method of contraception.

2) drmeletis.com/Publications/Common_Nutrient_Depletions_Caused_by_Pharmaceuticals.pdf

Common Nutrient Depletions Caused by Pharmaceuticals ALTERNATIVE & COMPLEMENTARY THERAPIES—FEBRUARY 2007 Chris D. Meletis, N.D., with Nieske Zabriskie, N.D. Estrogen and Progestins Hormone replacement therapy (HRT) is a common prescription for menopausal women. These estrogen/progestin combinations are used to decrease symptoms associated with menopause, such as hot flashes, vaginal dryness, sleep disturbances, and fatigue. In the United States, from 1999 to 2002, approximately 15 million women were on HRT, annually accounting for 90 million prescriptions per year.2 The Women’s Health Initiative study was widely publicized in 2002; this study demonstrated that HRT increases the risk of coronary heart disease, breast cancer, and strokes.3 Following the publication of the study, HRT prescriptions decreased by approximately 32 percent in 2003.4 Oral contraceptive pills (OCPs) also contain estrogen/progestin combinations. OCPs have been shown to increase the risk of cardiovascular events as well as breast, cervical, and liver cancer. 5,6 Estrogen/progestin hormones have been shown to deplete many nutrients. Research suggests that estrogens deplete several B vitamins significantly. Oral estradiol decreases pyridoxine (vitamin B6) and albumin in postmenopausal women.7 This vitamin B6 deficiency is believed to be associated with a disruption in tryptophan metabolism.8 Other research indicates that oral contraceptives deplete riboflavin (vitamin B2), folic acid, cobalamin (vitamin B12), ascorbic acid (vitamin C), and zinc.9 Other research indicates a decrease by 40 percent of both folic-acid and serum B12 levels with oral contraceptive use.10 Clinically, lower folic-acid levels appear to correlate with increased prevalence of abnormal Papanicolaou (Pap) smear results. In addition, studies have shown that estrogen supplementation increases magnesium uptake into bone and soft tissue, causing lowered blood magnesium levels. With low magnesium intake, this alters the calcium-to-magnesium ratio. This change in ratio can cause an increase in coagulation, which may lead to an increased risk of thrombosis that occurs with estrogen supplementation. 11

2A) home.caregroup.org/clinical/altmed/interactions/Drug_Classes/Oral_Contracept.htm

Oral Contraceptives drug class: Oral Contraceptives (Birth Control Pills) trade names: Brevicon®, Demulen®, Enovid®, Genora®, Levlen®, Loestrin®, Micronor®, Modicon®, Nordette®, Norinyl®, Ortho-Novum®, Ovcon®, Ovral®, Ovrette®, Triphasil®, etc. type of drug: Various combinations of artificial female hormones, specifically estrogens and progestins or only progestins. Note: hormone replacement therapy and oral contraceptives employ different forms of estrogen and/or progestin. used to treat: Pregnancy prevention; menstrual irregularities and endometriosis. overview of interactions: nice summary of various vitamin and mineral deficiencieds induced by OCs

Vitamin C

3) www.ajcn.org/content/28/5/550.full.pdf

Oral contraceptives and ascorbic acid’ Jeny M. Rivers,2 Ph.D. ABSTRACT Plasma, leukocyte, and platelet ascorbic acid levels are decreased in women ingesting oral contraceptive steroids. Studies have shown that it is the estrogenic component of the oral contraceptive agents that is associated with the decreased ascorbic acid concentrations. Urinary excretion of ascorbic acid does not appear to be increased by the steroids. Although serum levels of copper are increased by estrogens and oral contraceptives, ascorbic acid catabolism does not appear to be increased (unpublished). Our preliminary data on tissue uptake of ascorbic acid suggest that changes in tissue distribution are one possible answer for the observed effects of the steroids on blood levels of ascorbic acid. Am. J. Clin. Nutr. 28: 550-554, 1975.

Serotonin Metabolism in OCs

4) www.ncbi.nlm.nih.gov/pubmed/7140295 Contraception. 1982 Aug;26(2):193-204. Serotonin metabolism and depression in oral contraceptive users. Shaarawy M, Fayad M, Nagui AR, Abdel-Azim S. Serotonin and nicotinic acid ribonucleotide metabolic pathways of tryptophan metabolism were studied before and after tryptophan load test in thirty women using oral contraceptive steroids for a period of 2 to 5 years. Ten of them were suffering from depression. Another ten healthy women participated in this study as a control group. Twenty-four-hour urinary excretion of serotonin, 5- hydroxyindole acetic acid and total 5-hydroxyindoles were estimated as indices of serotonin pathway metabolites, while xanthrenate excretion was determined as an index of tryptophan oxygenase pathway. Plasma cortisol, urinary 17-oxosteroids and 17- hydroxycorticosteroids were determined to assess adrenal cortical function. Urinary creatinine output was assayed to check the adequacy of 24-hr urine collection. The changes induced by oral contraceptive steroids on tryptophan and corticosteroid metabolism were correlated with the associated depression. Changes in serotonin metabolism were demonstrated in the depression group before and after tryptophan load test, while in the non-depression group before and after tryptophan load test, while in the non-depression group, these changes were only demonstrated after tryptophan load test. Results indicated the alteration in tryptophan metabolism are usually well compensated in the non-depression group but may accentuate or precipitate the development of depression in susceptible women.

Depression

5) www.ncbi.nlm.nih.gov/pubmed/37042 Compr Psychiatry. 1979 Jul-Aug;20(4):347-58. Oral contraceptives and depressive symptomatology: biologic mechanisms. Parry BL, Rush AJ. The biological mechanisms through which oral contraceptives influence the central nervous system and produce depression were examined. Oral contraceptives reduce the level of serotonin and norepinephrine available at the central adrenergic receptor sites, alter folate and B12 levels, and perhaps influence hypothalamic releasing hormone levels. The level of serotonin is influenced in the following manner. The estrogens in oral contraceptives increase tryptophan available for the brain to convert to serotonin and tryptamine. Depression is associated with lower levels of serotonin, tryptamine, and perhaps tryptophan in the brain. Estrogens in oral contraceptives may also alter pryridoxal phosphate which in turn affects the production of serotonin. Oral contraceptives possibly lower norepinephrine levels by 1) decreasing tyrosine; 2) influencing coenzymes necessary to norepinephrine production; and 3) increasing monoamine oxidase levels. Oral contraceptives apparently inhibit the metabolism of folate and B12, and lower levels of these substances are associated with depressive symptoms. Decreased norepinephrine and serotonin levels may inhibit the release of gonadotrophin-releasing hormones, and these hormones may in turn influence behavior. Recommendations to clinicians were: 1) patients should be screened for a history of depression prior to prescribing oral contraceptives; 2) pill users should be monitored for depression; and 3) 25 mg daily of pyxidoxine should be administered if a patient taking oral contraceptives is deficient in B6. Pyridoxine

B6 deficiency , and Depression from BCP s

6) www.sciencedirect.com/science/article/pii/S0140673673913597 The Lancet Volume 301, Issue 7809, 28 April 1973, Pages 897-904

EFFECT OF PYRIDOXINE HYDROCHLORIDE (VITAMIN B6) UPON DEPRESSION ASSOCIATED WITH ORAL CONTRACEPTION P. W. Adams, V. Wynn, D. P. Rose1, M. Seed, J. Folkard and R. Strong The known association between combined estrogen-progestagen oral contraceptive (o.c.) administration and abnormalities of tryptophan and vitamin-B6 metabolism has been investigated in a group of 22 depressed women whose symptoms were judged to be due to the effects of o.c. 11 of these women showed biochemical evidence of an absolute deficiency of vitamin B6. In a double-blind crossover trial this group of women responded clinically to the administration of pyridoxine hydrochloride. The remaining 11 women showed no such response. Placebo administration was without effect. Possible mechanisms for depression due to o.c. use and its treatment with pyridoxine hydrochloride are discussed.

B6 deficiency and depression

7) www.ncbi.nlm.nih.gov/pmc/articles/PMC1129699/pdf/westjmed00295-0095b.pdf www.ncbi.nlm.nih.gov/pmc/articles/PMC1129699/?page=1
www.ncbi.nlm.nih.gov/pubmed/9076409

West J Med. 1975 March; 122(3): 255–256. Letter: more on oral contraceptives.D A Rockwell

8) ajp.psychiatryonline.org/cgi/content/abstract/130/11/1217

Oral Contraceptives, Pyridoxine, and Depression FRANK WINSTON M.B.B.S.1 Am J Psychiatry 130:1217-1221, November 1973 Taking steroid hormones for the control of ovulation may be associated with depressive mood changes in women who are predisposed to depression. The author postulates that such depression may in some cases be due to inhibition of the synthesis of biogenic amines in the central nervous system as the result of a functional pyridoxine deficiency caused by the estrogen in the oral contraceptives. It is suggested that this depression might be prevented or alleviated by the administration of supplementary vitamin B6. lower beta carotene Vitamin A in OC users Tyrosine Metabolism in OCs

9) www.ncbi.nlm.nih.gov/pubmed/7266825
Neuropsychobiology. 1981;7(4):192-200.

Effect of oral contraceptives on tryptophan and tyrosine availability: evidence for a possible contribution to mental depression. Møller SE. Abstract The plasma concentrations of branched-chain and aromatic amino acids, free tryptophan, and kynurenine have been determined in oral contraceptive users and comparable controls. There were no differences between progestogen users and controls in either of the biochemical measurements. The estrogen-progestogen users showed elevated plasma levels of total tryptophan and decreased levels of tyrosine. Mestranol was less potent than ethinylestradiol on the effect on plasma tyrosine. Mestranol was less potent than ethinylestradiol on the effect on plasma tyrosine. There was a clear trend that the incidence of adverse reactions was related to the decrease in tyrosine levels. The plasma ratio of tryptophan to competing amino acids was increased in the estrogen-progestogen users, whereas the ratio of tyrosine to competitors was severely decreased suggesting a decreased brain tyrosine concentration. It is suggested that a substrate-limited reduction in brain noradrenaline synthesis may contribute to the occurrence of depressive symptoms in susceptible individuals on estrogen-progestogen contraceptives.

10) www.ncbi.nlm.nih.gov/pubmed/7869850 Life Sci. 1995;56(9):687-95. Tyrosine metabolism in users of oral contraceptives. Møller SE, Maach-Møller B, Olesen M, Madsen B, Madsen P, Fjalland B. Department of Clinical Pharmacology, St. Hans Psychiatric Hospital, Roskilde, Denmark. Brain noradrenaline takes part in the regulation of several brain functions. The formation of brain noradrenaline depends on brain tyrosine (Tyr) levels, which associates with the ratio in plasma of Tyr to other large, neutral amino acids (LNAA). Tyr metabolism has been studied in users of the new generation combined oral contraceptives (OC) and comparable controls at the follicular, mid-cycle, and luteal phases of the menstrual cycle. OC users showed significantly increased plasma Tyr transaminase activity, and significantly decreased plasma Tyr and Tyr/LNAA levels at mid-cycle and luteal phase, whereas plasma total 3-methoxy-4-hydroxyphenylglycol (MHPG) was not affected. Following an oral protein load, the area under the curve in plasma of Tyr and Tyr/LNAA in OC users at the luteal phase were 43% and 29%, respectively, of control levels. The results suggest that the decreased Tyr availability to the brain in OC users may result in a substrate-limited reduction of brain noradrenaline formation, which, secondarily, may contribute to disturbances of mood, coping mechanisms, and appetite in susceptible subjects.

Nervous Depression From OC’s

11) www.ncbi.nlm.nih.gov/pubmed/4108553
Am J Obstet Gynecol. 1971 Dec 15;111(8):1013-20. Nervousness and depression attributed to oral contraceptives: a double-blind, placebo-controlled study. Goldzieher JW, Moses LE, Averkin E, Scheel C, Taber BZ. letter about depresion caused by OC’s Dr Rose – Tryptophan Disturbed and B6 Deficiency

12) www.ncbi.nlm.nih.gov/pubmed/5021929
www.ajcn.org/content/25/5/494.long
Am J Clin Nutr. 1972 May;25(5):494-8. Effects of dietary vitamin B 6 deficiency and oral contraceptives on the spontaneous urinary excretion of 3-hydroxyanthranilic acid. Price SA, Rose DP, Toseland PA.

13) www.ncbi.nlm.nih.gov/pubmed/4683526
Metabolism. 1973 Feb;22(2):165-71. Urinary excretion of quinolinic acid and other tryptophan metabolites after deoxypyridoxine or oral contraceptive administration. Rose DP, Toseland PA. Abstract The urinary excretion of quinolinic acid and some other tryptophan metabolites has been determined after a 2-g L-tryptophan load in a deoxypyridoxine-treated subject, in 20 women receiving estrogen-containing oral contraceptives, in and a control group of 12 women taking no steroids. In both situations there were increases in the excretion of quinolinic acid and 3 -hydroxyanthanillic acid, as well as 3-hydroxykynurenine and xanthurenic acid. These changes were reversed by pyridoxine administration and are considered to reflect an inhibitory effect of estrogens and deoxypyridoxine on vitamin B6 dependent enzymes. Although the principal enzyme of the tryptophan-nicotinic acid ribonucleotide pathway affected by imparied pyridoxal phosphate function is kynureninase, the present results are consistent with the existence of an unidentified enzyme beyond the formation of 3 hydroxyanthranilic acid requires the coenzyme. Increased typtophan metabolites in urine suggesting B6 deficiency.

14) www.ncbi.nlm.nih.gov/pubmed/6889807
Bermond P. Acta Vitaminol Enzymol. 1982;4(1-2):45-54. Therapy of side effects of oral contraceptive agents with vitamin B6. Bermond P. Studies carried out in different countries during the last 15 years have provided evidence that supplementation with (or excess of) estro-progestational hormones may be accompanied by an increased urinary excretion of tryptophan metabolites, as happens in pyridoxine deficiency. Further methods of assessment of vitamin B6 in humans have confirmed an impaired status in women using hormonal contraception. Disturbances in the metabolism of tryptophan have been shown to be responsible for such symptoms as depression, anxiety, decrease of libido and impairment of glucose tolerance occurring in some of the OCA users. Administration of 40 mg of vitamin B6 daily not only restores normal biochemical values but also relieves the clinical symptoms in those vitamin B6 deficient women taking OCA’s.

15).
http://www.ncbi.nlm.nih.gov/pubmed/3676217
British Journal of Nutrition (1986), 56, 363-367 363
The effect of oral contraceptives on the apparent vitamin B, status in some Sudanese women BY ELTAYEB Y. SALIH, ASMA A. ZEIN AND RIAD A. BAYOUMI Faculty of Medicine, University of Khartoum, PO Box 102, Khartoum, Sudan (Received 4 April 1986 – Accepted 23 April 1986) Women using OC are known to develop functional and apparent biochemical manifestations similar to those observed with vitamin B6 deficiency and our observations are in agreement with those earlier findings (Rose et al. 1973a, b; Adams et al. 1973; Nobbs, 1974), even though a low dose of OC was used by women in this study. The depression and other symptoms and signs usually associated with the use of OC were also observed in Sudanese women and the incidence of such symptoms and signs was more frequent in the OC users who had biochemical evidence of vitamin B, deficiency. Altered tryptophan metabolism

16) www.ncbi.nlm.nih.gov/pubmed/1244084
Acta Vitaminol Enzymol. 1975;29(1-6):151-7. Effects of oral contraceptives on tryptophan metabolism and vitamin B6 requirements in women. Brown RR, Rose DP, Leklem JE, Linkswiler HM. To evaluate the effect of oral contraceptive usage on the nutritional requirement for vitamin B6, control women and oral contraceptive users were depleted of vitamin B6 for 1 month followed by a month of repletion with 0.8, 2.0, or 20.0 mg of pyridoxine hydrochloride per day. At weekly intervals a number of indices of vitamin B6 nutrition were measured. Marked elevation in excretion of tryptophan metabolites occurred in oral contraceptive users after tryptophan loads. The excretion of metabolites after oral loading doses of L-kynurenine (which bypasses tryptophan oxygenase) was elevated in oral contraceptive users indicating that abnormal metabolism of tryptophan was not due only to induced tryptophan oxygenase. The data indicate that use of oral contraceptives does not generally change the requirement for vitamin B6 but rather produces a specific change in activity of enzymes beyond kynurenine in the pathway of tryptophan metabolism.

Frank Psychosis from OCs

17) www.ncbi.nlm.nih.gov/pubmed/4179717
South Med J. 1969 Feb;62(2):190-2. Psychosis associated with the use of oral contraceptive agents. Kane FJ Jr.
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full text explains biochemistry of B6 deficiency from BCPs

8) www.ajcn.org/content/24/6/684.long www.ncbi.nlm.nih.gov/pubmed/5581004 Am J Clin Nutr. 1971 Jun;24(6):684-93. Vitamin B 6 metabolism in users of oral contraceptive agents. I. Abnormal urinary xanthurenic acid excretion and its correction by pyridoxine. Luhby AL, Brin M, Gordon M, Davis P, Murphy M, Spiegel H
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B6, B12 and Folate

19) www.ncbi.nlm.nih.gov/pubmed/6568271
J Nurse Midwifery. 1984 Nov-Dec;29(6):386-90.
Effects of oral contraceptives on vitamins B6, B12, C, and folacin. Veninga KS. This article examines the effects of oral contraceptives (OCs) on the metabolism of vitamin B6, folacin, vitamin B12, and vitamin C and outlines educational strategies through which nurse-midwives can improve their clients’ nutritional health. Evidence of vitamin B6 deficiency has been found among combination OC users in numerous studies. Derangement of tryptophan metabolism occurs within 1 month of initiation of OC use. OCs also may cause a deficiency of pyridoxal phosphate, a coenzyme needed for the tryptophan-nicotinic acid pathway. It is recommended that OC users take 1-1.5 mg/day of supplemental vitamin B6; new OC users should take 5 mg/day until plasma levels of 1.5-2 mg have been achieved. It has also been noted that OCs impair folacin metabolism, as evidenced by folacin deficiency in serum and an increase in urinary formiminoglutamic acid secretion.

20) www.ncbi.nlm.nih.gov/pubmed/769494
Adv Clin Chem. 1976;18:247-87.

Effects of oral contraceptives on vitamin metabolism.
Anderson KE, Bodansky O, Kappas A. Literature on the effects of oral contraceptives (OCs) on vitamin metabolism is reviewed. OCs have been reported to markedly increase serum levels of Vitamin-A. OCs may induce a thiamine deficiency and lower levels of Vitamin-B2. Concentrations of ascorbic acid in platelets, white cells, plasma, and urine are decreased by OCs. Decreased plasma and red blood cell concentrations of folic acid have been reported in OC users, though it does not appear that absorption of folate polyglutamate is affected. OC users may develop megaloblastic anemia because of folic acid deficiency. OCs have been reported to markedly reduce serum levels of Vitamin-B12. Some OC users who excrete abnormal amounts of tryptophan metabolites have some degree of true Vitamin-B6 deficiency. Evidence of altered tryptophan metabolism and/or absolute Vitamin-B6 deficiency has been found in emotionally depressed women taking OCs. OCs, especially estrogens, produce tryptophan metabolism abnormalities in the great majority of users.

Folate Deficiency and Megaloblastic Changes in Cervical Epithelium

21) www.ncbi.nlm.nih.gov/pubmed/7587577 Zhonghua Fu Chan Ke Za Zhi. 1995 Jul;30(7):410-3. Megaloblastic changes in cervical epithelium associated with oral contraceptives and changes after treatment with folic acid]. Article in Chinese] Li X, Ran J, Rao H. Source Second Affiliated Hospital of Shanxi Medical College, Taiyuan. Abstract OBJECTIVE: Megaloblastic changes in cervical epithelium occurred in 29 women in the oral contraceptive group (28.7%). CONCLUSIONS: Oral contraceptives reduced folate storage in the body and resulted in megaloblastic changes in cervical epithelium. This condition was improved with folic acid therapy.

22) www.ncbi.nlm.nih.gov/pubmed/47028
Lancet. 1975 Mar 8;1(7906):561-4. Vitamins and oral contraceptive use. Wynn V.

23) www.ncbi.nlm.nih.gov/pubmed/625357
Ned Tijdschr Geneeskd. 1978 Feb 4;122(5):146-50. [Folic acid deficiency, the “pill” and the withheld anamnesis]. [Article in Dutch] Mendes de Leon DE. Abstract 3 women, 25, 26, and 37 years of age, developed folic acid deficiencies during use of contraceptive agents. One patient used a depot preparation, while the other two used combination preparations. In addition, excessive alcohol use, smoking, malnutrition, and a latent case of sprue were involved in bringing about the folic acid deficiency.

24) www.ncbi.nlm.nih.gov/pubmed/1921842
Med Monatsschr Pharm. 1991 Aug;14(8):244-7. [Folic acid and vitamin deficiency caused by oral contraceptives]. [Article in German] Bielenberg J. Abstract Recently there have been reports that long-term use of estrogen- containing oral contraceptives (OCs) can induce folic acid and vitamin B deficiency which can lead to hematopoiesis. The symptoms are paleness, forgetfulness, sleeplessness, and euphoric and depressive states. This deficiency occurs when serum folic content falls below 8 nmol/1 or 3 ng/ml. According to a nutrition group blood folic acid level declined up to 40% in patients taking OCs. In a Sri Lanka study of healthy women aged 20-45 taking Ovulen 50 (.05 mg of ethinyl estradiol and 1 mg of ethynodiol diacetate) folic acid level dropped in the 1st 6 months stabilizing at 2.2 ng/ml in those from the lowest social classes and at 2.9 ng/ml in those from privileged classes. Prophylactic substitution of folic acid in the diet was recommended by WHO, but it is less effective since it appears in the diet as polyglutamate that has to be broken down to absorbable monoglutamate. A US study found that taking OCs for 60 months resulted in a 40% reduction of the vitamin B12 serum level, while vitamin B12 concentrations in erythrocytes and peripheral blood stayed normal. Vitamin B12 helps recover tetrahydrofolic acid from N- methyltetrahydrofolic acid. Possibly this is another manifestation of OC-induced folic acid hypovitaminosis. OCs can also influence tryptophan metabolism reducing its blood concentration whereby less 5-hydroxytryptamine (serotonin) is produced. This results in headache, concentration decreases irritability, and sleep disturbances. In addition, lower riboflavin (vitamin B2) and thiamin concentration in erythrocytes was reported after using OCs.

Peripheral Neuropathy

25) www.ncbi.nlm.nih.gov/pubmed/2540115 Isr J Med Sci. 1989 Mar;25(3):142-5. Folic acid deficiency, megaloblastic anemia and peripheral polyneuropathy due to oral contraceptives. Kornberg A, Segal R, Theitler J, Yona R, Kaufman S. Source Department of Hematology, Assaf Harofeh Medical Center, Zerifin, Israel. Abstract A 34-year-old woman developed megaloblastic anemia and peripheral polyneuropathy following the use of oral contraceptives for 4 years. Low levels of folic acid and vitamin B12 were found. Both the complete recovery after therapy with the vitamins, and the absence of other causes of vitamin B12 and folate deficiency, suggest that the vitamin deficiencies were caused by the oral contraceptives and resulted in the rare combination of megaloblastic anemia and polyneuropathy. The poor response to vitamin B12 alone, and the development of anemia and polyneuropathy 4 months after cessation of vitamin B12 therapy suggest that folate deficiency was the primary problem.

B12 and folate Deficiency

26) www.ncbi.nlm.nih.gov/pubmed/6133702 Curr Concepts Nutr. 1983;12:73-87. Drugs and vitamin B12 and folate metabolism. Lindenbaum J. Abstract Deficiency of either folic acid or vitamin B12 may interfere with DNA synthesis and result in megaloblastic anemia or other conditions. A number of cases of megaloblastic anemia due to folate deficiency have been reported in women taking OCs.

27) www.ncbi.nlm.nih.gov/pubmed/112009 Haematologica. 1979 Apr;64(2):190-5. Megaloblastic anemia due to folic acid deficiency after oral contraceptives. Barone C, Bartoloni C, Ghirlanda G, Gentiloni N. Abstract A young patient was hospitalized for megaloblastic anemia due to folate deficiency. Laboratory exams and functional tests demonstrated that the deficiency was due to hormonal contraception treatment on which the woman had been for the last consecutive 11 months. The disease subsided completely following withdrawal of oral contraception (OC), and normal hematological values were maintained after that, suggesting that no malabsorption was present. Cases of megaloblastic anemia in women on OC are rare, and the phenomenon may be related to prolonged and uninterrupted drug assumption.

28) www.ncbi.nlm.nih.gov/pubmed/952302 Am J Obstet Gynecol. 1976 Aug 15;125(8):1063-9. Effect of oral contraceptives on nutrients. III. Vitamins B6, B12, and folic acid. Prasad AS, Lei KY, Moghissi KS, Stryker JC, Oberleas D. Plasma pyridoxal phosphate (B6) and red cell and serum folate were lower in subjects using OCA’s in the upper socioeconomic group as compared to levels in the control subjects. Reduction in erythrocyte glutamic oxalacetic transaminase (EGOT) activity and elevation in the EGOT-stimulation test were observed in subjects using OCA’s in both upper and lower socioeconomic groups. These observations suggest a relatively deficient state with respect to vitamins B6 and folic acid in OCA users.

Modern OC’s – B12 levels Lower

29) www.ncbi.nlm.nih.gov/pubmed/12593896 Eur J Obstet Gynecol Reprod Biol. 2003 Mar 26;107(1):57-61. Serum folate and Vitamin B12 levels in women using modern oral contraceptives (OC) containing 20 microg ethinyl estradiol. The effects of modern oral contraceptives (OC) on serum concentrations of folate and cobalamin are controversial.Case-control study on the cobalamin and folate status of 71 healthy female nulligravidae using “low dose” OC for >or=3 months and 170 controls. RESULTS:OC-users showed significantly lower concentrations of cobalamin than controls.

B12 Metabolism

30) www.ncbi.nlm.nih.gov/pubmed/3976378 Acta Obstet Gynecol Scand. 1985;64(1):59-63. Oral contraceptives and the cobalamin (vitamin B12) metabolism. Hjelt K, Brynskov J, Hippe E, Lundström P, Munck O. Abstract The mean concentrations of serum (S)-cobalamin (vitamin B12) and S-unsaturated B12 binding capacity (UBBC) were significantly decreased in 101 women (mean age: 30.4 years) taking oral contraceptives (OC) of the combination type, compared to 113 controls. OC users more frequently showed decreased concentrations of S-cobalamin (less than 200 pmol/l) than did their controls.

31) www.ncbi.nlm.nih.gov/pmc/articles/PMC1862844/?tool=pubmed www.ncbi.nlm.nih.gov/pubmed/7037144

Can Med Assoc J. 1982 Feb 1;126(3):244-7. Oral contraceptives: effect of folate and vitamin B12 metabolism. Shojania AM. Abstract Women who use oral contraceptives have impaired folate metabolism as shown by slightly but significantly lower levels of folate in the serum and the erythrocytes and an increased urinary excretion of formiminoglutamic acid. The vitamin B12 level in their serum is also significantly lower than that of control groups. Clinicians are advised to ensure that women who shop taking “the pill” because they wish to conceive have adequate folate stores before becoming pregnant. Since pregnant women are predisposed to the development of folate deficiency, it would be necessary when stopping the pill for desire of pregnancy to take folate supplements before becoming pregnant.

OC’s Decrease Testosterone 50%

32) www.medicalnewstoday.com/releases/35663.php

Birth Control Pill Could Cause Long-Term Problems With Testosterone,
Endocrinology Article Date: 04 Jan 2006 Claudia Panzer, Dr. Andre Guay, study co-author and Director of the Center for Sexual Function/Endocrinology in Peabody, MA

“This work is the culmination of 7 years of observational research in which we noted in our practice many women with sexual dysfunction who had used the oral contraceptive but whose sexual and hormonal problems persisted despite stopping the birth control pill,” said Dr. Irwin Goldstein, a urologist and senior author of the research. “There are approximately 100 million women worldwide who currently use oral contraceptives, so it is obvious that more extensive research investigations are needed. The oral contraceptive has been around for over 40 years, but no one had previously looked at the long-term effects of SHBG in these women. The larger problem is that there have been limited research efforts in women’s sexual health problems in contrast to investigatory efforts in other areas of women’s health or even in male sexual dysfunction.” Oral contraceptives decrease circulating levels of androgens by direct inhibition of androgen production in the ovaries and by a marked increase in the hepatic synthesis of sex-hormone binding globulin, the major binding protein for gonadal steroids in the circulation. The combination of these two mechanisms leads to low circulating levels of “unbound” or “free” testosterone.

Effects on Thyroid and Testosterone Hormone Levels

33) www.nlm.nih.gov/pubmed/18477491
Contraception. 2008 Jun;77(6):420-5.

Effects of an oral contraceptive containing 30 mcg ethinyl estradiol and 2 mg dienogest on thyroid hormones and androgen parameters: conventional vs. extended-cycle use.Sänger N, Stahlberg S, Manthey T, Mittmann K, Mellinger U, Lange E, Kuhl H, Wiegratz I. This study was conducted to investigate the effects of an oral contraceptive containing 30 mcg ethinyl estradiol and 2 mg dienogest on thyroid hormones and androgen parameters. Thyroid and androgen parameters were measured in 59 women treated with a monophasic combined oral contraceptive containing 30 mcg ethinyl estradiol and 2 mg dienogest (EE/DNG) either conventionally (13 cycles with 21 days of treatment+7 days without hormones) or according to an extended-cycle regimen (four extended cycles with 84 days of continuous administration of EE/DNG, followed by a hormone-free interval of 7 days). Blood samples were taken on Days 21-26 of the preceding control cycle and on Days 19-21 of the 3rd and 13th conventional cycle, or on Days 82-84 of the first and fourth extended cycle.

RESULTS: The serum concentrations of thyroxine-binding globulin were elevated by about 65% in both treatment regimens. Likewise, both groups showed an increase in total triiodothyronine (T3) and total thyroxine (T4) by 30-40%, and no change in free T4. In both groups there was a rise of sex hormone-binding globulin by 210-230% after 3 months and by 220-250% after 12 months. The levels of total testosterone were reduced by about 40% and those of free testosterone by 55-65% after 3 and 12 months. OCs decrease testosterone by 60% and

Decrease Acne

34) www.nlm.nih.gov/pubmed/6084924/ Acta Derm Venereol. 1984;64(6):517-23.\ Serum total and unbound testosterone and sex hormone binding globulin (SHBG) in female acne patients treated with two different oral contraceptives. Palatsi R, Hirvensalo E, Liukko P, Malmiharju T, Mattila L, Riihiluoma P, Ylöstalo P. Serum total an unbound testosterone (T) and sex hormone binding globulin (SHBG) levels were studied in fifty-four female acne patients before treatment and during the treatment by two different oral contraceptives, the other containing 0.150 mg desogestrel plus 0.03 mg EE and the other 0.150 mg levonorgestrel plus 0.03 mg EE. Pretreatment values were abnormal in 57% of the patients. A borderline significant correlation between the severity of acne and SHBG was found. Ater six months’ treatment a 250% increase in SHBG was seen in desogestrel/EE group and no significant change in SHBG in levonorgestrel/EE group. However, at the same time serum free testosterone fell 60% in both treatment groups. Acne improved significantly in both treatment groups. It is likely that the improvement was in connection with the free testosterone decrease and the improvement was better in the desogestrel/EE group where also SHBG elevation was seen. OC’s Long Term Effects On Testosterone

35) www.medpagetoday.com/OBGYN/HRT/2423
Birth Control Pills May Produce Protracted Effects on Testosterone Levels By Katrina Woznicki, Published: January 03, 2006

Dr. Panzer and colleagues noted that earlier research has shown increases in sex hormone-binding globulin levels with oral contraceptive use to be associated with a concomitant 40% to 60% decrease in free testosterone levels. The investigators suggested that prolonged exposure to the synthetic estrogens found in oral contraceptives may trigger permanent changes in gene expression that leads to the elevated levels of sex hormone-binding globulin. Sex Hormone Binding Globulin 4 times higher in OC users – later after stopping

36) www.ncbi.nlm.nih.gov/pubmed/16409223 J Sex Med. 2006 Jan;3(1):104-13.

Impact of oral contraceptives on sex hormone-binding globulin and androgen levels: a retrospective study in women with sexual dysfunction. Panzer C, Wise S, Fantini G, Kang D, Munarriz R, Guay A, Goldstein I. Oral contraceptives (OCs) have been the preferred method of birth control because of their high rate of effectiveness. OC use, however, has been associated with women’s sexual health complaints and androgen insufficiency. OC use is associated with a decrease of androgen ovarian synthesis and an increase in the production of sex hormone-binding globulin (SHBG). There have been limited studies assessing SHBG values after discontinuation of OC use. To retrospectively investigate SHBG levels before and after discontinuation of OC use. Sex hormone-binding globulin values were compared at baseline, while on the OC, and well beyond the 7-day half-life of SHBG at 49-120 (mean 80) days and >120 (mean 196) days after discontinuation of OCs. A total of 124 premenopausal women with sexual health complaints for >6 months met inclusion/exclusion criteria. Three groups of women were defined: (i) “Continued-Users” (N = 62; mean age 32 years) had been on OCs for >6 months and continued taking them; (ii) “Discontinued-Users” (N = 39; mean age 33 years) had been on OCs for >6 months and discontinued them; and (iii) “Never-Users” (N = 23; mean age 36 years) had never taken OCs. RESULTS: Sex hormone-binding globulin values in the “Continued-Users” were four times higher than those in the “Never-User” group (mean 157 +/- 13 nmol/L vs. 41 +/- 4 nmol/L; P < 0.0001). Despite a decrease in SHBG values after discontinuation of OC use, SHBG levels in “Discontinued-Users” remained elevated in comparison with “Never-Users” (N = 26; P < 0.0001 for >120 days). CONCLUSION: In women with sexual dysfunction, SHBG changes in “Discontinued-Users” did not decrease to values consistent with “Never-Users.” Long -term sexual, metabolic, and mental health consequences might result as a consequence of chronic SHBG elevation. Does prolonged exposure to the synthetic estrogens of OCs induce gene imprinting and increased gene expression of SHBG in the liver in some women? Prospective research is needed. Increased Thyroid Binding Globulin

37) www.ncbi.nlm.nih.gov/pubmed/15293894
Toldy E, Lo¨csei Z, Rigo E, Kneffel P, Szabolcs I, Kovacs GL.

Comparative analytical evaluation of thyroid hormone levels in pregnancy and in women taking oral contraceptives: a study from an iodine deficient area. Gynecol Endocrinol 2004;18: 219–26. Increase of serum thyroxine binding globulin (TBG) resulting from estrogen action may lead to problems in thyroid diagnostics. The necessity of a distinct reference range has emerged for free thyroid hormones in midterm and late pregnancy as well as in the use of oral contraceptives, especially in iodine-deficient areas.

Vitamin A metabolism

38) www.ajcn.org/content/27/2/125.full.pdf

Effects of oral contraceptives on vitamin A metabolism in the human and the rat’ David L. Yeung,2 Ph.D. ABSTRACT In this study, the effects of oral contraceptives (OC) on vitamin A metabolism in the human and rat were examined. Data obtained from the human study showed that the mean plasma vitamin A levels and basal body temperature of females taking OC were significantly higher than control subjects. However, there was no statistical correlation between the vitamin A levels and basal body temperature. The elevation of plasma vitamin A levels in the OC subjects was found not to be due to variation in dietary vitamin A intake or blood hematocrit values. The physiologic implication of the higher plasma vitamin A levels in the OC subjects is not clear. In the rat, Ovral, an OC agent, given as a saline suspension by stomach intubation daily for 4 weeks did not have any effect on plasma vitamin A. However, it markedly raised the liver vitamin A depletion rate and the rate of utilization of the vitamin. This indicated that rats given OC had a higher vitamin A requirement level. Whether oral contraceptives do alter vitamin A requirement in the human remains to be investigated. Am. J. Clin. Nutr. 27: 125-129, 1974. ascorbic acid decreased

39) http://www.ncbi.nlm.nih.gov/pubmed/9076409

Eur J Clin Nutr. 1997 Mar;51(3):181-7.
Use of oral contraceptives and serum beta-carotene. Berg G, Kohlmeier L, Brenner H. Source Department of Epidemiology, University of Ulm, This study investigates the influence of oral contraceptives (OC) on the serum concentration of beta-carotene, which may in turn affect the risk of cardiovascular diseases due to its antioxidative impact. DESIGN: Cross-sectional epidemiologic study. Examinations included a detailed questionnaire on medical history and lifestyle factors, a 7 day food record, and blood samples. SETTING: National health and nutrition survey among healthy people living in private homes in West Germany in 1987-1988. SUBJECTS: Nonpregnant and nonlactating women aged 18-44 (n = 610). RESULTS: Overall, the use of OC was negatively associated with serum beta-carotene concentration in bi- and multivariable analyses after adjustment for age, smoking, alcohol consumption, dietary intake of beta- carotene, use of vitamin supplements, body mass index, pregnancies, and serum concentrations of total triglyceride and cholesterol. A strong interaction between OC use and age on beta-carotene concentration was observed. While no relationship between OC use and serum beta-carotene was seen in the youngest age-group (18-24 y), there was a modest but significant negative association between OC use and beta-carotene levels among 25-34 y old women. The use of OC was associated with a strong decrease in beta-carotene levels among 35-44 y old women. The interaction between OC use and age could partly be explained by age dependent use of OC with higher estrogen content. CONCLUSIONS: OC use seems to be strongly related to serum beta-carotene levels, particularly among women above the age of 35. Further studies are needed to clarify the underlying mechanisms of this association and its implications for health risks of OC use. Beta- carotene, a provitamin with antioxidant effects, may substantially reduce the risk of coronary artery disease and acute myocardial infarction. A cross-sectional epidemiologic study involving 610 West German women 18-44 years of age indicates that oral contraceptive (OC) use has a negative impact on serum levels of beta-carotene. 195 respondents (32%) were current OC users, 322 (53%) were past users, and 91 (15%) had never used OCs. Median serum beta-carotene levels were significantly lower in current OC users (25.1 mcg/dl) than in past (32.5 mcg/dl) and never users (31.2 mcg/dl). The percentage of women with beta-carotene levels below the desirable value of 21.5 mcg/dl was significantly higher in the current OC use group (34%) than in the 2 other groups combined (21%), yielding an overall odds ratio (OR) of 1.9 (95% confidence interval, 1.3-2.8). The strength of the association between OC use and decreased beta- carotene increased with age (OR of 1.5 for women 18-24 years, 1.9 for those 25-34 years, and 3.4 for 35-44-year old women). In addition, the decrease of beta-carotene was larger for OCs containing 50 mcg of ethinyl estradiol than for low-dose formulations. Also observed were significant associations between serum beta-carotene levels and smoking, alcohol intake, body mass index, triglycerides, nutrient intake, and total cholesterol levels. Although further studies are required to identify the mechanisms underlying the OC- beta-carotene association and define its implications for women’s health, OC users should be advised to consume vegetables rich in beta-carotene. Higher copper levels in OC users

Increased Copper

40) www.ncbi.nlm.nih.gov/pubmed/9805216
Eur J Clin Nutr. 1998 Oct;52(10):711-5.
Effect of oral contraceptive progestins on serum copper concentration. Berg G, Kohlmeier L, Brenner H. Source Department of Epidemiology, University of Ulm, Germany. Abstract OBJECTIVES: Recent epidemiologic studies have shown an increased mortality from cardiovascular diseases in people with higher serum copper levels. Even though higher serum copper concentration in women using oral contraceptives is well known, there is still uncertainty about the influence of newer progestin compounds in oral contraceptives on serum copper concentration. This issue is of particular interest in the light of recent findings of an increased risk of venous thromboembolism in users of oral contraceptives containing newer progestins like desogestrel compared to users of other oral contraceptives. DESIGN: Cross-sectional epidemiologic study. Examinations included a detailed questionnaire on medical history and lifestyle factors, a seven day food record, and blood samples. SETTING: National health and nutrition survey among healthy people living in private homes in West Germany in 1987-1988. SUBJECTS: Nonpregnant and nonlactating women aged 18-44 y (n = 610). RESULTS: Overall, the use of oral contraceptives was positively associated with serum copper concentration in by bi- and multivariable linear regression models with log-transformed values of serum copper concentration as dependend variable and oral contraceptive preparations and potential confounding variables as independent variables. Serum copper concentration in women using oral contraceptives varied more strongly by different progestin compounds than by estrogen contents. The highest increase of serum copper was seen in women using oral contraceptives containing antiandrogen progestins (55%; 95% CI: 37-76%), followed by desogestrel (46%; 95% CI: 36-56%), norethisteron/lynestrenol (42%; 95% CI: 29-57%), and levonorgestrel (34%; 95% CI: 24- 45%). CONCLUSION: While elevated serum copper concentration was found in users of all types of oral contraceptives, elevation was more pronounced among women taking oral contraceptives with antiandrogen effective progestins like antiandrogens or third generation oral contraceptives containing desogestrel. Further investigation is required to shed light on the possible role of high serum copper concentration in increasing cardiovascular or thrombotic risk of women using oral contraceptives. High serum copper concentration–a well-known effect of oral contraceptive (OC) use–has been linked to increased mortality from cardiovascular disease. The influence of OCs containing newer progestins has not been investigated, however. This concern was addressed in a 1987-88 cross-sectional epidemiologic study of 610 nonpregnant, nonlactating West German women 18-44 years of age. 195 women (32.1%) were current OC users, but only 152 of these women were able to cite the name of the formulation they were taking. In 70% of cases, the OC contained less than 45 mcg of ethylestradiol (median dose, 32.4 mcg). The most common progestin components were desogestrel (41%) and levonorgestrel (30%). Mean serum copper concentration was higher among users of all types of OCs than among non-users, but this concentration varied more strongly according to the OC’s progestin compound than its estrogen content. The greatest increase in serum copper (55% compared with non-users) was recorded in users of OCs containing anti-androgen progestins, followed by desogestrel (46%), norethisterone/lynestrenol (42%), and levonorgestrel (34%). The increase in serum copper was more pronounced in women taking OCs containing 45 mcg or less of ethylestradiol than in users of OCs with a high estrogen dose. In the regression models, the different progestin compounds alone explained 28% of the total variance in serum copper concentration. Further investigation of OC-induced increases in serum copper concentration and their impact on cardiovascular risk are warranted.

41) www.ncbi.nlm.nih.gov/pubmed/6791490

Am J Clin Nutr. 1981 Aug;34(8):1479-83.

Zinc and copper nutriture of women taking oral contraceptive agents. Vir SC, Love AH. A cross-sectional and follow-up study of young women taking oral contraceptive agents revealed a marked increase in serum copper levels. This increase was significant after the taking of oral contraceptive agents for 3 months. No significant effect of oral contraceptive agents on serum zinc and hair levels or copper were observed. There was no correlation between duration of oral contraceptive agent therapy and zinc or copper concentrations in serum or hair. Serum and hair concentration of zinc or copper were also not significantly correlated. It is well known that OC (oral contraception) may provoke changes in metal metabolism. This study examines the effects of OC use in serum and hair level of both zinc and copper. The study involved a control group of 24 women, aged 18-20, who had never been on OC; a cross-sectional experimental group of 33 women, aged 18-23, who had been using combined OC for at least 3 months; a follow-up experimental group of 12 women, aged 18-22, who were about to start OC treatment for the first time, and who were examined again at 3 and at 6 months. Blood samples and hair samples were collected and analyzed with the Vir and Love method. Mean serum copper concentration was significantly higher in OC users; hair copper values were also higher, but the difference was not a significant one. Mean serum zinc levels were slightly lower, and hair zinc levels slightly higher in OC users; differences between users and nonusers, however, were not significant. No significant correlation was found between duration of OC treatment and serum and hair metal values. In the follow-up experimental group mean serum copper level increased at 3 months of OC treatment, and mean hair copper values decreased; there were no significant differences at 3 and at 6 months. Mean serum zinc concentration and mean hair zinc concentration also decreased in the control group, but the decline was not significant. No significant correlation was found between serum and hair concentration of zinc or copper in the control or in the experimental group. These findings are consistent with others reported in the published literature. The biological significance of the rise in serum copper levels, and of the slight alteration in serum zinc level after OC use is still not known. ———————————————

42) www.ditchthepill.org/ Ditch the Pill

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Venous Thromboembolism

43) www.ncbi.nlm.nih.gov/pubmed/20659364 J Fam Plann Reprod Health Care. 2010 Jul;36(3):123-9. Risk of venous thromboembolism and the use of dienogest- and drospirenone-containing oral contraceptives: results from a German case- control study. Dinger J, Assmann A, Möhner S, Minh TD. The study confirms that COC use is associated with an increased risk of VTE. ————————————————

IUD is preferable to the OC

44) www.acog.org/from_home/publications/press_releases/nr06-20-11-1.cfm

ACOG News Release June 20, 2011 IUDs, Implants Are Most Effective Reversible Contraceptives Available Washington, DC — Long-acting reversible contraceptive (LARC) methods—namely intrauterine devices (IUDs) and implants—are the most effective forms of reversible contraception available and are safe for use by almost all reproductive-age women, according to a Practice Bulletin released today by The American College of Obstetricians and Gynecologists (The College). The new recommendations offer guidance to ob-gyns in selecting appropriate candidates for LARCs and managing clinical issues that may arise with their use.”LARC methods are the best tool we have to fight against unintended pregnancies, which currently account for 49% of US pregnancies each year,” said Eve Espey, MD, MPH, who helped develop the new Practice Bulletin. “The major advantage is that after insertion, LARCs work without having to do anything else. There’s no maintenance required.” According to a December 2009 Committee Opinion released by The College, LARCs should be offered as first-line contraceptive methods and encouraged as options for most women. “The benefits of IUDs and the contraceptive implant in preventing unplanned pregnancy could be profound with widespread adoption of these methods, and ob-gyns are in a great position to effect change,” Dr. Espey said. Dr. Espey chairs the ACOG working group for long-acting reversible contraceptives and is a liaison member on the Committee for Underserved Women. She is a board member of the Society for Family Planning and for Physicians for Reproductive Choice and Health. Additionally, Dr. Espey is Associate Dean of Students at the University of New Mexico and has chaired the UNM School of Medicine Curriculum Committee, working to promote incorporation of reproductive health in the medical school curriculum.

45) www.healthnews.com/en/news/IUDs-Implants-Advocated-for-Birth-Control/2jpSZHe7P6OB_LB5PA_eLl/?pageNr=1#
IUDs, Implants Advocated for Birth Controlby Amy Norton, Last updated June 21, 2011

46) www.metrolic.com/on-birth-control-171319/
On Birth Control According to Espey, both IUDs available on the United States market (ParaGard IUD, which is made out of copper and it is effective for 10 years and Mirena, which is effective for only 5 years) prevent the fertilized egg to attach to the uterine wall and they have tremendous safety records and no patient has complained yet about them.

47) www.rxlist.com/script/main/art.asp?articlekey=146028
IUDs May Be Underused Form of Birth Control Report Suggests Intrauterine Devices and Implantable Contraceptives Should Be Used by More Women By Denise Mann WebMD Health News Reviewed By Laura J. Martin, MD

48) www.wired.com/magazine/2011/07/ff_iud/3/
Contraceptive Comeback: The Maligned IUD Gets a Second Chance By Jennifer Couzin-Frankel Email Author July 15, 2011 | Wired August 2011

49) findarticles.com/p/articles/mi_m0CYD/is_10_35/ai_62827621/

IUD’s Bad Rap Persists, Despite Data by Erik L. Goldman
Despite two decades’ worth of research showing that currently marketed IUD\s are safe, effective, cost efficient, reversible, and patient pleasing, many American physicians still view the IUD as a bad bet. As a result, less than 1% of U.S. women seeking contraception in 1995 received IUDs. Worldwide, however, well over 80 million women use the device safely.

whqlibdoc.who.int/publications/2004/9241562668.pdf
The Medical eligibility criteria for contraceptive use -WHO KNOWN THROMBOGENIC MUTATIONS (e.g. Factor V Leiden; Prothrombin mutation; Protein S, Protein C and Antithrombin deficiencies)

www.paragard.com/health_care_professional/global/pdf/Prescribing-Info.pdf
Prescribing information paragard copper T IUD

www.arhp.org/MethodMatch/details.asp?productId=2
Copper T IUD Information and Video from Association of Reproductive Health Professionals – East 1901 L Street, NW, Suite 300, Washington, DC 20036 (202) 466-3825 | ARHP@arhp.org

www.youtube.com/watch?v=MSF-1wbuRiI&feature=player_embedded
Video on IUD Copper T imbed video

www.nejm.org/doi/full/10.1056/NEJM200201313460517
Copper Intrauterine Devices and Tubal Infertility among Nulligravid Women
N Engl J Med 2002; 346:376-377January 31, 2002
A growing body of literature indicates that IUD use is far safer than previously thought. David Hubacher, Ph.D.Family Health International, Research Triangle Park, NC 27709

IUD-More cost effective over long term

www.ncbi.nlm.nih.gov/pubmed/7702112
Am J Public Health. 1995 Apr;85(4):494-503.
The economic value of contraception: a comparison of 15 methods.
Trussell J, Leveque JA, Koenig JD, London R, Borden S, Henneberry J, LaGuardia KD, Stewart F, Wilson TG, Wysocki S, et al. Source Office of Population Research, Woodrow Wilson School of Public and International Affairs, Princeton University, NJ 08544, USA. Abstract
OBJECTIVES: The purpose of the study was to determine the clinical and economic impact of alternative contraceptive methods. METHODS: Direct medical costs (method use, side effects, and unintended pregnancies) associated with 15 contraceptive methods were modeled from the perspectives of a private payer and a publicly funded program. Cost data were drawn from a national claims database and MediCal. The main outcome measures included 1-year and 5-year costs and number of pregnancies avoided compared with use of no contraceptive method.
RESULTS: All 15 contraceptives were more effective and less costly than no method. Over 5 years, the copper-T IUD, vasectomy, the contraceptive implant, and the injectable contraceptive were the most cost-effective, saving $14,122, $13,899, $13,813, and $13,373, respectively, and preventing approximately the same number of pregnancies (4.2) per person. Because of their high failure rates, barrier methods, spermicides, withdrawal, and periodic abstinence were costly but still saved from $8933 to $12,239 over 5 years. Oral contraceptives fell between these groups, costing $1784 over 5 years, saving $12,879, and preventing 4.1 pregnancies.

IUD- Does Not Impair Fertility after removal

www.ncbi.nlm.nih.gov/pubmed/17241835
Contraception. 2007 Feb;75(2):88-92. Epub 2006 Nov 14.
Use of IUD and subsequent fertility–follow-up after participation in a randomized clinical trial. Hov GG, Skjeldestad FE, Hilstad T. Source Department of Epidemiology, SINTEF Health Research and Institute of Laboratory Medicine, Children’s and Women’s Health, Norwegian University of Technology and Science, N-7465 Trondheim, Norway. Abstract
PURPOSE: Although the IUD has been a contraceptive method for about 50 years, how it affects subsequent fertility remains controversial. The aim of our study was to examine time to pregnancy, pregnancy outcome and the need for infertility workup in a cohort of previous copper IUD users.
MATERIALS AND METHODS: From May 1993 to April 1995, 957 women were included in a prospective cohort IUD study in the city of Trondheim, Norway. From this randomized clinical trial, we identified 205 women eligible for study participation. Group A comprised 109 women who removed their IUD for purposes of planning to become pregnant, while Group B comprised 96 women who became pregnant or planned pregnancy after a complicated IUD use. Data were collected through a postal questionnaire. All information from the questionnaires was validated against data kept in the medical record at the general practitioner’s office or in the hospital record of women who became pregnant or started an infertility workup. All analyses were done using SPSS. RESULTS: In Group A, 93.6% (102/109) of the women became pregnant. Time to conception was unaffected by parity order, duration of use and age at time for removal of the IUD. Among the seven women who did not conceive, four women cancelled pregnancy plans, while three women started an infertility workup. The distribution of intra-/extrauterine pregnancies did not differ between Groups A and B. However, significantly more pregnancies were terminated as induced abortions in Group B. The two women (2%) who did not conceive in Group B did not start an infertility workup. CONCLUSION: In line with results from other studies, there is no evidence that prior use of a copper-containing IUD increases the risk for impaired fertility regardless of the reason for removal.

www.paragard.com/hcp/references
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