Pain-relieving medications such as non-steroidal anti-inflammatory drugs (NSAIDs) can help reduce pain (Kennedy 2005; Laufer 2003). However, NSAIDs can lead to gastric ulcers and may inhibit ovulation (Kennedy 2005).
Oral contraceptives. Endometriosis symptoms often resolve during menopause and pregnancy and hormonal therapies are used to produce similar states to treat this condition (Winkel 2003). Suppressing the activity of the ovaries via the use of oral contraceptives is one of the most commonly used medical treatments (Laufer 2003; Kennedy 2005), though this also prevents pregnancy and may be associated with other side effects (CDC 2013; Winkel 2003). In addition, oral contraceptives fail to control endometriosis pain in approximately 20–25% of patients (Giudice 2010).
GnRH agonists. For women who cannot obtain satisfactory relief with NSAIDs and oral contraceptives after 6 months of therapy, other medications may be tried (Schenken 2012). These medications include gonadotropin-releasing hormone (GnRH) agonists, such as leuprolide (Lupron®) (Laufer 2003; Schenkin 2012; Kennedy 2005; Giudice 2010). One effect of GnRH agonists is lowered estrogen levels, which may be of benefit for women with endometriosis since estrogen stimulates the growth of endometriotic tissue (Giudice 2010). GnRH agonists can cause significant bone loss after a few months of therapy, which is only partially reversible. However, adding small amounts of estrogens to the treatment to maintain a low, stable estrogen level can help retain bone density (Giudice 2010; Hornstein 1998; Kennedy 2005).
Danocrine. Danocrine (Danazol®) is another effective treatment option. It is a synthetic hormone that works by creating a lower estrogen, higher androgen environment resulting in a reduction of endometriosis lesions (Selak 2007; Cottreau 2003; Laufer 2003). Although effective, it can cause weight gain, depression, reduced breast size, deepening of the voice, skin rash, and increased body hair (Laufer 2003). In addition, research suggests Danazol may increase the risk of ovarian cancer (Cottreau 2003).
Progestins (synthetic, unnatural progesterone-like drugs). A fourth possible therapy is a synthetic progestin, such as Provera® (medroxyprogesterone acetate) (Laufer 2003; Schenken 2012). Progestins are synthetic versions of the hormone progesterone (Spark 2009). These medications can cause weight gain, depression, bloating, and irregular bleeding, as well as increase cardiovascular risk (Laufer 2003).
The flaws of synthetic progestins. A major problem with progestins is that they are not natural to the human body. In other words, their chemical structure differs from that of the progesterone humans produce naturally. Progestins are patented, synthetic drugs that protect against estrogen-induced endometrial cancer (UMMC 2013a). Progestins are meant to function like natural progesterone, but a huge body of data indicates potential for adverse side effects. For example, some data suggests natural progesterone may confer a protective effect against breast cancer (Holtorf 2009; Wood 2007; Zhou 2013; Chlebowski 2013), whereas progestins have been linked with increased risk (Zhou 2013; Chlebowski 2013; Liang 2010; Baker 1994; Vehkavaara 2001).
Compared to synthetic progestin that stimulates breast cell proliferation, natural progesterone has demonstrated a protective effect. There are at least 17 studies showing that progestins significantly increase breast cell replication and growth (Chlebowski 2013; Vehkavaara 2001; Jeng 1992; Kalkhoven 1994; Papa 1990; Jordan 1993; Catherino 1993; Cline 1998; Cline 1996; Menendez 2005; Seeger 2005; Murkes 2011; Wood 2009; Neubauer 2013; Murkes 2012; Chang 1995; Foidart 1998). In stark contrast, at least 11 studies have shown that natural progesterone does not induce estrogen-stimulated breast cell proliferation (Neubauer 2013; Murkes 2012; Chang 1995; Foidart 1998; Mueck 2003; Inoh 1985; Barrat 1990; Malet 2000; Laidlaw 1995; van Leeuwen 1991; Fournier 2005).
Numerous studies have demonstrated an increased risk of breast cancer with the use of synthetic progestins (Rossouw 2002; Vehkavaara 2001; Porch 2002; Fournier 2008; Plu-Bureau 1999). However, the use of natural (bioidentical) progesterone has not been associated with an increased risk of breast cancer (Holtorf 2009; Wood 2007; Zhou 2013; Chlebowski 2013; Fournier 2008; Micheli 2004). Quite to the contrary, research has revealed that natural progesterone decreases the risk of breast cancer. In a study published in the journal Breast Cancer Research and Treatment, 80,000 postmenopausal women using various forms of hormone replacement therapy (HRT) were followed for more than 8 years. Women who used estrogen in combination with synthetic progestin had a 69% increased risk of breast cancer compared to women who had never used HRT. However, for women who used natural progesterone in combination with estrogen, the increased risk of breast cancer was completely eliminated with a significant reduction in breast cancer risk compared with synthetic progestin use (Micheli 2004). In another investigation, these same researchers found a 40% increased risk of breast cancer for women who used estrogen with synthetic progestin (Fournier 2008). Interestingly, in women who used estrogen combined with natural progesterone, there was a promising trend toward a reduced risk of breast cancer compared to women who never used HRT (Fournier 2008). In essence, natural progesterone appeared to protect women against the development of breast cancer. These findings confirm work done six years earlier that found a trend toward a reduced risk of breast cancer in 1150 women using natural progesterone compared to non-users of progesterone (Cowan 1981).
Compelling research offers further insight into natural progesterone’s ability to defend against breast cancer. In a fascinating study, scientists administered estrogen alone, natural progesterone alone, estrogen plus natural progesterone, or placebo to 40 women prior to surgery to remove a breast lump. The hormones were applied topically to the breast for about 12 days before surgery. As expected, when given alone, estrogen caused a 62% increase in breast cell proliferation rates compared to placebo. Conversely, the addition of natural progesterone to estrogen resulted in a significant decrease in the estrogen-induced increase in breast cell proliferation rates. Even more impressive was the finding that the group receiving natural progesterone alone had a nearly 76% lower breast cell proliferation rate compared to the placebo group (Mueck 2003).
Bioidentical Hormone Replacement Therapy
Since a relative excess of estrogenic activity is a major driving force in endometriosis, maintaining hormonal balance may help ensure that endometrial tissue, either normal or ectopic, does not grow in unchecked fashion (Bulun 2006; Brosens 2011). The combination of regular blood testing and bioidentical hormone replacement therapy may help women achieve such a hormonal balance. Bioidentical hormones are designed to be identical to the hormones that the body makes (Holtorf 2009; Moskowitz 2006). Doctors can check for hormonal imbalances and design a natural bioidentical hormone regimen to maintain hormone levels in the right proportions (Holtorf 2009; Moskowitz 2006). In the context of discussions about bioidentical hormones, the term “natural” when appearing before the name of a hormone, for example “natural estrogen,” should be interpreted to mean that the molecular structure of the compound in question is identical to that which occurs naturally in the human body.
Bioidentical progesterone is especially intriguing in the context of endometriosis. Progesterone is a key hormone in endometriosis, as it counters the effects of estrogen by inhibiting harmful inflammatory mediators (eg, interleukin-8) and inducing apoptosis (programmed cell death) (Reis 2013). Using bioidentical progesterone may be an effective approach to the treatment of endometriosis (Jain 2012). Bioidentical progesterone may cause fewer side effects than the synthetic progestins used in conventional hormone replacement therapy (Jain 2012; Holtorf 2009; Moskowitz 2006).
Natural progesterone has numerous other benefits over progestins as well. The Women’s Health Initiative, a large randomized clinical trial, demonstrated that the addition of synthetic progestins to estrogen therapy resulted in a substantial increase in the risk of heart attack and stroke (Rossouw 2002). In one trial published in the Journal of the American College of Cardiology, researchers studied postmenopausal women with a history of heart attack or coronary artery disease. The women were given estrogen in combination with either natural progesterone or synthetic progestin. After 10 days of treatment the women underwent exercise treadmill tests. Compared to the synthetic progestin group, the amount of time it took to produce myocardial ischemia (reduced blood flow to the heart) on the exercise treadmill was substantially improved in the natural progesterone group (Register 1998).
Atherosclerosis (hardening of the arteries) is a leading cause of heart disease. Several studies have determined that synthetic progestin promotes the formation of atherosclerosis (Adams 1997; Morey 1997; Houser 2000). The story is quite different for natural progesterone, where multiple animal studies have shown that natural progesterone inhibits the process of atherosclerosis (Houser 2000; Adams 1990; Tall 2008). To illustrate, scientists fed monkeys with surgically induced menopause a diet known to cause atherosclerosis for a total of 34 months. The scientists then divided the monkeys into groups that received estrogen alone, estrogen plus synthetic progestin, or a control group that did not receive hormones. The control group developed substantial atherosclerotic plaque. The administration of estrogen resulted in a 72% decrease in atherosclerotic plaque compared to the control group (Houser 2000). Treatment with synthetic progestin yielded disturbing results. The group of postmenopausal monkeys that received estrogen combined with synthetic progestin had a similar amount of atherosclerotic plaque as the control group. This showed that synthetic progestin completely reversed estrogen’s inhibitory effects on the formation of atherosclerosis (Houser 2000). In contrast, when the same investigators administered natural progesterone along with estrogen, no such inhibition of estrogen’s cardiovascular benefit was seen (Fåhraeus 1983).
Readers interested in learning more about bioidentical hormone restoration are encouraged to review Life Extension’s Female Hormone Restoration protocol.
Surgical treatment of endometriosis can either be a first-line therapy or an option when medical therapy fails (Giudice 2010; Laufer 2003; UMMC 2013b; NYT 2013). Laparoscopic ablation of implanted endometrial tissue reduces pain in about 65% of cases (Giudice 2010). However, recurrence of pain requiring additional therapy occurs within 12 months for up to 60% of women (Giudice 2010; Laufer 2003). A more invasive surgical option is a hysterectomy with removal of both ovaries (bilateral salpingo-oophorectomy). This treatment more effectively treats pain from endometriosis, as shown by a study in which 10 years after undergoing this type of surgery, only 10% of women had recurrent symptoms (Mounsey 2006).
Improving fertility is an important consideration for women with endometriosis who want to become pregnant (Schenken 2012; Giudice 2010). Laparoscopic destruction of ectopic endometrial tissue along with removal of any adhesions has been found to improve fertility in women with minimal or mild endometriosis. Women receiving hormonal treatments for endometriosis show no significant effects on rates of pregnancy or live birth when compared to women receiving no treatment or a placebo (Giudice 2010). In-vitro fertilization, artificial insemination, and other fertility-promoting techniques may help women with endometriosis become pregnant (Giudice 2010).