Menopause

*Sigh* so I guess it's time to grow up and start acting like the expert. Don't you people know that I'm a Toys 'R' Us kid??? A pox upon you, responsibility! From hell's heart, I stab at thee!!!

Inspired by one of my commenters, I will begin a short series on the status of hormone replacement therapy for the treatment of menopausal symptoms. The first segment gives a brief overview of menopause and past treatments for the symptoms associated with menopause, as well as an overview of the shifts in social context for the "change of life". Future installments will address recent findings and their implications for women's health, as well as that all-important question--- is estrogen safe???

Click below for the fun part, replete with sexist ads from the 1960s. Make sure you read the ad text.

The Transition to Menopause

Menopause is defined as the cessation of ovarian function. It occurs at the average age of 50 in women, is accompanied by a decrease in circulating levels of estrogen and progesterone associated with the loss of follicular activity, and, following one full year of amenorrhea the start of menopause is retrospectively designated as after final menses. The transition to menopause, referred to as perimenopause, begins roughly two to eight years earlier and extends one full year past final menses. Cycles may become shorter and levels of follicle stimulating hormone rise to compensate for a decreased number of ovarian follicles. Middle perimenopause is characterized by a transitional period where cycles become shorter and intervals between them increase. Levels of ovarian hormones become erratic and other symptoms such as hot flashes and uterine bleeding may become increasingly common. During late perimenopause-- or the year following the last menstrual cycle-- ovulation no longer occurs and estradiol (E2), the principal circulating estrogen, is no longer produced by follicles. The ovary continues to manufacture testosterone and estrone (E1, which is now the primary circulating estrogen), and the primary source of E2 is the aromatization of testosterone and androstenedione. Progesterone continues to be produced in smaller amounts by the adrenals (Greendale and Sowers, 1997).

History of Postmenopausal Hormone Therapy: Historically, the menopause was generally framed as a positive event for women who, having endured the rigors and burdens of childbearing and menses, had now earned the right to focus on themselves:

After a certain number of years, woman lays aside those functions with which she has been endowed for the perpetuation of the species, and resumes once more that exclusively individual life which has been hers when a child… The evening of her days approaches, and if she has observed the precepts of wisdom, she may look forward to a long and placid period of rest, blessed with health, honored and loved with a purer flame than any which she inspired in the bloom of youth and beauty.

As indicated in the above quote by George Napheys in 1869, in a book entitled The Physical Life of Woman: Advice to the Maiden, Wife, and Mother (Seaman, 2003), the change of life was viewed favorably, as a return to a carefree lifestyle. Menopausal symptoms such as hot flashes were viewed as a natural part of the transition. Treatments for menopausal symptoms had primarily consisted of herbals, and more recently a selection of belladonna, cannabis, or opium. In the 1890’s Merck offered these chemicals along with the flavored powder Ovariin for the treatment of menopausal symptoms and other ovarian ills (Merck, 1899). Aptly named, Ovariin was made by dessicating and pulverizing cow ovaries, and may have been the first substance commercially available for treatment of menopausal symptoms that was derived from animal sources. The first report detailing the use of ovarian extracts to relieve vasomotor symptoms of menopause occurred in 1897 (Speroff, 1999). E1 was isolated in 1929 (Butenandt and von Ziegner, 1930; Doisy et al., 1930), and in 1930 estriol glucuronide, which converts to E2 upon hydrolysis, was isolated from horse urine (Collip, 1930). Emminen, the first replacement therapy to contain conjugated estrogens, was extracted from the urine of pregnant women and became commercially available in 1933. In 1937 progesterone was used to prevent ovulation in rabbits, beginning the hunt for marketable progestins (Speert, 1980). Diethylstilbestrol (DES) was first marketed in 1939 as a far more potent estrogen than Emminen, which could not be made fast enough to keep up with demand. Ayerst Laboratories began marketing Premarin in 1942, which would eventually become the number one form of estrogen replacement therapy in the United States, and the estrogenic component of Prempro, a combination of Premarin and Provera, which eventually became the most widely dispensed drug in the US.

Premarin was five times as expensive as the competing product, which led to an ad campaign that marketed Premarin as an “upscale” therapy (Seaman, 2003). Initial advertisements for this drug, which would eventually become the most prescribed estrogen therapy, showed women in a highly glamorized light, surrounded by handsome men, happy families, and having fun. This campaign was successful, leading Ayerst to initiate an educational program for physicians on menopausal symptoms and therapies. Premarin use skyrocketed in the 1960s partly due to the highly successful “Keep her on Premarin” ad campaign that mixed authoritarianism with sexism, replacing the historical outlook of menopause as a natural transition with one of a deficient state to be treated for the rest of a woman’s life.

Ironically, Premarin was placed on the market one year after reports suggesting that estrogen may cause cervical cancer in animals (Seaman, 2003).


References:
Butenandt A, von Ziegner E., 1930. On the Physiological Effectiveness of Crystallized Female Sex Hormones in the Allen-Doisy Test. Studies on the Female Sex Hormone. J Phys Chem 188:1-10.

Collip JB. 1930. Ovarian stimulating hormone of placenta. Can Med Assoc J 22:215-219.

Doisy EA, Veler CD, Thayer SJ. 1930. Preparation of crystalline ovarian hormone from urine of pregnant women. J Biol Chem 86:499-509.

Greendale GA, Sowers M. 1997. The Menopause Transition. Menopause and Hormone replacement Therapy 26:261-277.

Merck Manual Diagnosis &Therapy. New York: Merck and Co.; 1899.

Seaman B. The Greatest Experiment Ever Performed on Women: Exploding the Estrogen Myth. New York, NY: Hyperion; 2003.

Speert H. Obstetrics and Gynecology in America: A History. Chicago: The American College of Obstetricians and Gynecologists; 1980.

Speroff L. Clinical Gynecologic Endocrinology and Infertility. 6th edition. Baltimore, MD: Williams and Wilkins; 1999.