Is history repeating itself?


An essay exploring the biological effects of hormonal birth control on multiple generations of humans

Diana West, Assistant Professor of Chemistry, Ave Maria University, Ave Maria, FL
Vicki Thorn, Founder, Project Rachel and Executive Director, National Office of Post-Abortion Reconciliation & Healing, Milwaukee, Wisconsin
Dr. Diana West, Assistant Professor of Chemistry

Dr. Diana West, Assistant Professor of Chemistry

In 1930, Pope Pius XI reaffirmed the Church’s two-millennia teaching on contraception in Casti Connubii (1). A generation later, Bl. Pope Paul VI in Humanae Vitae defined and predicted the consequences of a contraceptive mentality and explained why acceptable methods such as Natural Family Planning/Fertility Awareness respected the nature of the marital act (2). Subsequent Pontiffs have continued to contribute to deeper theological understanding for marriage and human dignity, most notably, St. Pope John Paul II’s Theology of the Body. Despite the Magisterium’s clear instruction on appropriate means of family planning, a Guttmacher survey (3) reported that among self-identified Catholic women (between ages 15-44 and sexually-active), 83% used contraceptive methods not sanctioned by the Church. As a significant proportion of women, Catholic and non-Catholic have used birth control over the past several decades, several scholars have delved into the social and spiritual consequences of a contraceptive society (4-8). This essay will instead explore the history and multi-generational biological fallout of hormonal contraceptives.

In 1936, Dr. Elizabeth Hunt published a medical editorial raising concerns over using natural estrogens to treat human skin disorders. Knowing that estrogens induced tumors in laboratory animals, Hunt asked, “…should not a woman be informed of the possible risk to which she is exposed[?]”(9). Shortly thereafter, two synthetic estrogens were developed by competing scientific teams: diethylstilbestrol (DES) (10) and ethinyl estradiol (EE2) (11). DES was prescribed to women to prevent miscarriages and premature births. While male workers occupationally exposed to DES developed breasts (12), few recognized this harbinger of future’s disturbing side effects. Decades later, vaginal cancer (adenocarcinoma) was linked to patients whose mothers’ used DES (13), and subsequent evidence of DES-induced cancer and fertility disorders led to its ban in 1971. By then, millions of women worldwide had taken DES; their children, exposed to DES in utero, were termed “DES daughters and sons” (14, 15). DES children later had children of their own, and “DES grandchildren” also experienced side effects of their grandmothers’ prescription (16,17). These observations implied that DES induced inheritable changes, and experimental evidence of DES-altered DNA via epigenetic modifications supports this hypothesis (18,19).

EE2, developed at the same time as DES, showed potential as a birth control hormone. Planned Parenthood founder Margaret Sanger backed a team of researchers to formulate the first birth control pill with mestranol, a derivative of EE2 (20,21). First available in 1960, the drug was quickly nicknamed “the Pill,” a general moniker used since then for most oral hormonal contraceptives. In 1969, Barbara Seaman, a pro-choice journalist-turned-activist, summarized her research on Pill-induced blood clots, mood disorders, and cancer in The Doctor’s Case Against the Pill (22). Senator Gaylord Nelson subsequently organized congressional hearings on Pill safety that were interrupted by young feminist protesters shouting questions such as: “Why are 10 million women being used as guinea pigs?” (23, 24). Like DES, EE2 was a recognized occupational hazard for pharmaceutical workers; male breast development and female fertility disorders were documented symptoms (25). Four decades after the Pill was first prescribed, the World Health Organization classified the combined estrogen-progestogen contraceptive as a Group 1 carcinogen (26, 27), a ranking shared with tobacco and asbestos. The Pill’s elevated risk of breast and cervical cancer was strong enough to warrant Group 1 classification, despite evidence of lowered ovarian/endometrial cancer risk. Some of today’s contraceptive formulations, with lower EE2 doses than the first Pill, still have a significant association with increased breast cancer risk (28, 29). Similar to DES, EE2 is also an environmental epigenetic DNA modifier (30) that may produce inheritable risks for Pill user’s children and grandchildren. Altered epigenetic DNA markers and increased cancer incidence were observed in EE2-exposed female rats and two subsequent generations of offspring (31). Dr. Craig Roberts and others have demonstrated that Pill-users were attracted to different men compared non-Pill-users (32,33), implying an unknown biological mechanism that may alter human evolution and mate choice. Some of the first Pill proponents became concerned about the unintended effects of synthetic hormones on human health and evolution. Dr. Carl Djerassi, nicknamed “father of the Pill,” admitted that the Pill’s use over several decades served as an incidental longitudinal side-effect study (34). Djerassi ironically suggested that pharmaceutical companies develop Natural Family Planning methods as the future for birth control (35). Dr. Alexander Sanger, Chair of International Planned Parenthood Council, wrote that Pill-users “…are taking reproductive risks that cannot be seen or measured” (36). Therefore, as we begin to understand the biological consequences of the synthetic hormones in contraceptives, the contraceptives upon which our society purportedly relies, we can’t help but think of the early whistle-blowers: should not a woman be informed of the possible risk to which she is exposed? Why are millions of women and men being used as guinea pigs?

References:
1. Pope Paul VI. (1968). Humanae Vitae.
2. Pope Pius XI. (1930). Casti Connubi.
3. Jones R.K.; Dreweke J. (2011). Countering Conventional Wisdom: New Evidence on Religion and Contraceptive Use, Guttmacher Institute.
4. Smith, J. E. (1993). Why Humanae vitae was right: A reader.
5. Grabowski, J. (2003) Sex and Virtue: An Introduction to Sexual Ethics.
6. Eberstadt, M. (2012) Adam and Eve after the Pill.
7. Klaus, H.; Cortes, M.E. (2015). “Psychological, social, and spiritual effects
of contraceptive steroid hormones.” The Linacre Quarterly, 82 (3), 282.
8. Klaus, H. (2017). “Fertility is Not a Disease.” Church Life Journal.
9. Hunt, E. (1936). “Oestrin in Toxic Goitre.” The Lancet, 1302.
10. Dodds, E.C. (1938). “Oestrogenic Activity of Certain Synthetic Compounds.” Nature.
11. Gaudilliere, J. (2005). “Better prepared than synthesized: Adolf Butenandt, Schering Ag and the transformation of sex steroids into drugs (1930–1946).” Stud. Hist. Phil. Biol. & Biomed. Sci. 36 612–644.
12. Scarff R.W., Smith C.P. (1942). “Proliferative and other lesions of the male breast in stilboestrol workers.” Br J Surg 29:393–396.
13. Herbst, A.L.; Ulfelder, H.; Poskanzer, D.C. (1971).“Adenocarcinoma of the vagina. Association of maternal stilbestrol therapy with tumor appearance in young women.” N Engl J Med. 284:878–881.
14. Hoover R.N.; Hyer, M.; Pfeiffer, R.M.; et al. (2011). “Adverse health outcomes in women exposed in utero to diethylstilbestrol.” N Engl J Med. 365:1304–1314.
15. For a summary of DES research, see the NIH DES Fact Sheet: https://www.cancer.gov/about-cancer/causes-prevention/risk/hormones/des-fact-sheet
16. McLachlan, J.A. (2006). “Commentary: Prenatal exposure to diethylstilbestrol (DES): a continuing story.” Int J Epidemiol, 35 (4): 868-870.
17. Kalfa, N.; Paris, F,; Soyer-Gobillard, M.O., et al. (2011). “Prevalence of hypospadias in grandsons of women exposed to diethylstilbestrol during pregnancy: a multigenerational national cohort study.” Fertil Steril. 95(8):2574-7.
18. McLachlan, J.A. (2016). “Environmental signaling: from environmental estrogens to endocrine-disrupting chemicals and beyond.”Andrology. 4(4):684-94.
19. Newbold, R.R.; Padilla-Banks, E.; Jefferson, W.N. (2006) Endocrinology. “Adverse effects of the model environmental estrogen diethylstilbestrol are transmitted to subsequent generations.”
20. Lednicer, D., ed. (1969). Contraception: the chemical control of fertility.
21. Marks, L. (2010). Sexual Chemistry: A History of the Contraceptive Pill.
22. Seaman, B. (1969). The Doctor’s Case Against the Pill.
23.Kling, W. “Senate Pill Probe Disrupted by Groups of Women Hecklers.” Chicago Tribune. 24 January 1970.
24. Seaman, B. “The Pill and I: 40 Years on, the Relationship Remains Wary”, New York Times. 25 June 2000.
25. Harrington, J.M.; Stein, G.F.; Rivera, R.O., et al. (1978). “The Occupational Hazards of Formulating Oral Contraceptives – A Survey of Plant Employees.” Archives Of Environmental Health: An International Journal Vol. 33, Iss. 1.
26. IARC. (1999). IARC monographs on the evaluation of carcinogenic risks to humans, volume 72, hormonal contraception and post-menopausal hormonal therapy.
27. IARC. (2006). IARC monographs on the evaluation of carcinogenic risks to humans,
volume 91, combined estrogen-progestogen contraceptives and combined estrogen progestogen menopausal therapy.
28. Beaber, E.F.; Buist, D.S.; Barlow, W.E.; et al. (2014). “Recent oral contraceptive use by formulation and breast cancer risk among women 20 to 49 years of age.” Cancer Res. 74(15):4078-89.
29. Beaber, E.F.; Malone, K.E.; Tang, M.T.; et al. (2014). “Oral contraceptives and breast cancer risk overall and by molecular subtype among young women.” Cancer Epidemiol Biomarkers Prev. 23(5):755-64.
147(6 Suppl):S11-7.
30. King, O.C.; van de Merwe, J.P.; McDonald, J.A. (2016). “Concentrations of levonorgestrel and ethinylestradiol in wastewater effluents: Is the progestin also cause for concern?” Environ Toxicol Chem. 35(6):1378-85.
31. de Assis, S.; Warri, A.; Cruz, M.I.; et al. (2012). “High-fat or ethinyl-oestradiol intake during pregnancy increases mammary cancer risk in several generations of offspring.” Nature Communications. 3: 1053.
32. Cobey, K.D.; Little, A.C.; Roberts, S.C. (2015). “Hormonal effects on women’s facial masculinity preferences: the influence of pregnancy, post-partum, and hormonal contraceptive use.” Biol Psychol. 104:35-40.
33. For a review see: Alvergne, A.; Lummaa, V. (2010). “Does the contraceptive pill alter mate choice in humans?” Trends Ecol Evol. 25(3):171-9.
34. Djerassi, C. (2001). This Man’s Pill: Reflections on the 50th Birthday of the Pill.
35. Djerassi, C. (1990). “Fertility Awareness: Jet-Age Rhythm Method” Science. 248:4959, 1061-1062.
36. Sanger, A. (2004). Beyond Choice.