Weight gain, of course, is the most commonly reported side effect of Depo-Provera which, after reading thousands of internet postings from Depo-Provera users and several friends that use/have used this drug, I believe the approximate weight gain was grossly underreported by Pharmacia & Upjohn. From considerable research, I've learned that the apparent reason for this weight gain is that medroxyprogesterone acetate interferes with glucose metabolism and serum lipids.
If the woman does not receive adequate amounts of Folic Acid, she could readily develop ASCUS, another side effect that is being reported with increasing frequency in relation to Depo-Provera usage on obgyn.net and in medical journals.
There is increasing evidence that medroxyprogesterone acetate interferes with serotonin levels in the brain where it is unable to properly bond with the progesterone receptors in the limbic region. I've read postings by several gynecologists who, rather than removing the source of the problem by discontinuing their patients' Depo-Provera injections, attempt to mask the problem by prescribing antidepressants such as Xanax or Zoloft.
Under Adverse Reactions (in the PDR), it states, "May cause acne, alopecia and hirsutism."- Physicians Desk Reference 2000. This problem has often been reported on obgyn.net and in various medical journals.
Not So Common Side Effects: Consult Doctor:
breast tenderness or discharge, numbness or pain in the arm or leg, pain in the chest, groin or leg, severe headache, stomach pain, sudden shortness of breath, unusual weakness or tiredness, vision or speech problems, yellowing of skin or eyes
Common Side Effects: No medical assistance usually needed:
changes in sexual desire or ability, changes in vaginal bleeding, facial hair growth, fluid retention and swelling, headache, increased sweating or hot flashes, loss of appetite or increase in appetite, mood changes (not limited to: anxiety, depression, frustration, anger) or emotional outbursts, pain or itching at the injection site, skin rash, stomach discomfort, weight gain or weight loss, vaginal yeast infection (irritation and white discharge)
The following side effects are listed in Contraceptive Technology by R. Hatcher et al, CPS, 1997 -- "Weight gain affects most women, averaging about 2.3 kg (5 lbs.) in the first year and varying after that; some women gain significantly more. The reasons are unclear, but it may be that by suppressing estrogen, there is a higher ratio of androgenic (male) hormones, muscle growth and increased appetite."
"Other side effects may include: acne, breast tenderness, headaches, nervousness, depression and loss of libido. The delay in return to fertility averages 3-6 months, but may be up to 18 months or more for a small number of women. Symptoms may persist 6-8 months or longer after the drug is discontinued."
Several books related to Depo-Provera, including Thomas J. Vecchio's Birth Control by Injection: The Story of Depo-Provera which, although praised by Planned Parenthood, essentially trivializes the side effects by quoting the results of Pharmacia & Upjohn's clinical trials. A closer examination, however, reveals that these clinical trials were conducted almost entirely in third world countries and among socio-economically-disadvantaged women in large metropolitan clinics and hospitals. Many of these women, particularly in totally male-dominated third world countries, welcomed the opportunity to "conceal" (Vecchio's quotes) their contraceptive use from their husbands. I would also imagine that most of these women were ignorant of the phamacokinetics of Depo-Provera and would be unlikely to relate the side effects to the physicians administering the trials. In places like Atlanta's Grady Hospital, the trial group was composed of women in the most desperate economic circumstances -- women who would also be unlikely to report the side effects of a totally free, long term, concealable contraceptive.
More importantly, Pharmacia & Upjohn apparently failed to conduct clinical trials among contemporary, comparatively well educated, middle and upper income American women. Pharmacia & Upjohn claims in their advertising, "DEPO-PROVERA has been used safely by millions of women in over 100 countries around the world for more than 30 years. Since its introduction in the United States, millions of American women have started using it." They fail to mention that only 1.1 million women are currently using Depo-Provera in the US, and that over 70% of all American women who have ever used Depo-Provera discontinue it's use within the first year due to it's side effects. - Obstetrics and Gynecology (1996;88:227-233).
Pharmacia & Upjohn also neglects to mention that a substantial number of those "millions of women in over 100 countries" receive their Depo-Provera through a US taxpayer-supported program administered by the World Health Organization and not because they selected Depo-Provera from among several possible choices.
I have read the results of scores of research studies, communicated with several gynecologists, compounding pharmacists and their professional organizations, and other health care professionals, as well as attorneys who are possibly preparing class action suits against Pharmacia & Upjohn in California.
In an article that appeared in Nutrition Science News, Richard N. Podell, M.D., a clinical professor of family medicine at the UMDNJ-Robert Wood Johnson Medical School in New Brunswick, NJ said, "Progestins, available by prescription, are heavily advertised to physicians. Not surprisingly, the majority of doctors prefer them. One gynecologist asked me without the slightest hint of irony, 'Why would you risk using natural progesterone when you can use the traditional drug?'"
First, and perhaps most importantly, it is important to recognize that Depo-Provera IS NOT progesterone. It is a progestin (or progestogen), a synthetic hormone-like substance that is created in the laboratory by Pharmacia & Upjohn in order to secure a patent. As I'm sure you know, naturally occurring hormones cannot be patented and therefore are not profitable for pharmaceutical companies to manufacture. The patent protects the manufacturer from competition and guarantees a profit when combined with a successful marketing strategy.
I don't think for a minute that any pharmaceutical company has any one person's good health as its primary concern. Pharmacia & Upjohn's primary concern is to recoup their costs for development and field trials and hopefully keep a drug on the market long enough to generate a substantial profit for their shareholders.
Pharmacia & Upjohn produce Depo-Provera by adding methyl and acetoxy (petrochemical) components to a progesterone molecule. The resulting drug is by no stretch of the imagination progesterone and only behaves like progesterone in certain respects.
In order for any drug to work, it has to be able to bind to receptors in the body. For illustrative purposes, a generic representation of the molecular structure of a drug is R1-CH3-CH3-R2, wherein R1 is one end of the chemical molecule that is able to bind to an open receptor (Receptor 1) in the body. the CH3 components are generic placeholders (and could represent any chemical groups), and R2 is the other end of the molecule that is able to bind to another receptor (Receptor 2) in the body.
Depo-Provera was designed in the lab to replicate progesterone and, once injected, the body would react to it as it would to an increased level of progesterone. This to some extent is true -- and this achieves the contraceptive effect of Depo-Provera -- but not always.
The R1 group of Depo-Provera and progesterone are the same, and that is how Depo-Provera can bind to the receptors in the pituitary gland, thus inhibiting the midcycle leutinizing hormone (LH) peak, which in turn inhibits ovulation. The R2 group in Depo-Provera, however, is different from that of natural progesterone and IS NOT able to bind to other receptors in the body that also depend on progesterone. Upon comparison of the molecular diagrams of Depo-Provera and natural progesterone, this difference in the R2 receptor sites becomes strikingly apparent.
I'm sure you know that a woman's reproductive organs are not the only system of the body dependent on proper hormonal balance. Other organs and systems that depend on progesterone are the brain (for proper regulation of serotonin levels), the skin, the skeletal system, the digestive system, the breasts, the pancreas, etc.
By being able to bind to the progesterone receptors, Depo-Provera causes what appears to be an overabundance of progesterone within the body. This provides biofeedback to the body to quit producing as much progesterone, and this is where problems begin. This lack of progesterone is responsible for a multiplicity of symptoms such as: painful, swollen breasts, headaches, diminished libido, anorgasmia, anxiety, moodiness, inability to concentrate, depression, food cravings, irritability, insomnia, cramps, emotional swings, weight gain, bloating, acne, painful joints, hot flashes, night sweats and others.
One of the other problems from the use of this chemical is with bone mineral density. Depo-Provera has been shown to lower ovarian estradiol production, which results in a loss of bone mineral density. Depo-Provera and other progestins may be why we are seeing such an increase in the occurrence of osteoporosis. Again, this is due to Depo-Provera's action of down regulating or shutting off the body's ability to produce progesterone. Progesterone is responsible for activating the osteoblasts and thus building new bones. Estrogen is getting a lot of press as being beneficial for osteoporosis, but as for beneficial effects, progesterone is more important.
There is an article from the Journal of Obstet Gynecol 1999 Feb; 93(2):233-8 entitled "Bone Mineral density in women using depot medroxy progesterone acetate for contraception" that addresses this exact point. The conclusion of the article states, "These results provide evidence that contraception with depot medroxyprogesterone acetate, particularly long-term use, may adversely affect bone mineral density levels in young women age 18-21 years" Interestingly, the group that the study looked at was 18 to 21-year-old women. Since finding that study, I have read several subsequent studies with broader age group representation which have reached similar conclusions.
Most of these studies claim that this bone mineral loss is reversible, but I question how one reverses bone mineral loss in a post menopausal woman without further manipulation of hormonal levels with synthetic progestins and estrogens.
Depo-Provera has been associated with cytological changes in cervical smears. Long term users of Depo-Provera have been observed to have high nuclear cytoplasmic ratios and hyperchromasia in parabasal metaplasia-like cells. Biopsies in these cases have shown epithelial atrophy often associated with acute inflammation. I can't help but wonder how many needless kolposcopies, biopsies and LEEP surgeries have been performed on women using Depo-Provera.
From an article entitled, "Cytological changes in cervical smears associated with prolonged use of depot-Medroxyprogesterone acetate," by Philip T. Valente, M.D. *, H. Daniel Schantz, M.B.A., C.T. (A.S.C.P.), Jose F. Trabal, M.D., Departments of Pathology and Obstetrics and Gynecology, University of Texas Health Science Center at San Antonio, San Antonio, Texas, published in Cancer, Volume 84, Issue 6, 1998. Pages: 328-334: "Hormonal effects have always played a significant role in gynecologic cytology. In atrophic and postpartum smears, interpretation may be complicated by large numbers of parabasal cells with high nuclear cytoplasmic ratios and hyper chromatic nuclei that mimic pre-cancerous lesions (squamous intraepithelial lesions, SILs). The authors have observed atrophic and post partum-like changes in patients receiving depot-medroxyprogesterone acetate for prolonged periods. These alterations may lead to diagnostic uncertainty or falsely suggest the presence of SIL."
"The immature cellular pattern seen in smears from long term depot-medroxyprogesterone acetate users led to difficulty in determining the diagnosis in some cases. ASCUS cases among users were associated with high nuclear cytoplasmic ratios and hyperchromasia in parabasal metaplasia-like cells. Biopsies in these cases showed epithelial atrophy, which was often associated with acute inflammation. In view of the fact that long term depot-medroxyprogesterone acetate administration may induce changes that mimic high grade SIL in a population already at high risk for SIL, there may be problematic cases in which diagnostic uncertainty is inevitable." - Cancer (Cancer Cytopathol) 1998;84:328-34 © 1998 American Cancer Society.
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