Early Menarche, a Risk Factor for Breast Cancer, Indicates Early Onset of Ovulatory Cycles*

Abstract

The associations between age at menarche and the hormonal patterns of adolescent menstrual cycles were investigated to obtain information as to why early menarche is an important risk factor for breast cancer. An initial group of 200 schoolgirls, 7-17 yr old, was investigated longitudinally 3 times at 1.5-yr intervals. A serum progesterone concentration in the latter part of the cycle exceeding 6.4 nmol/liter (2.0 ng/ml) was considered to signify an ovulatory cycle, and a concentration less than 1.6 nmol/liter (0.5 ng/ml) an anovulatory cycle. The frequency of ovulation depended significantly on both the time since menarche and the age at menarche (P less than 0.001 for both variables). Early menarche was associated with early onset of ovulatory cycles. The times from menarche until 50% of the cycles were ovulatory were about 1, 3, and 4.5 yr when the ages at menarche were less than 12.0, 12.0-12.9, and more than or equal to 13.0 yr, respectively. Girls with a menarcheal age below 12.0 yr had higher serum estradiol but lower testosterone and dehydroepiandrosterone concentrations than subjects with later menarche. The estradiol to dehydroepiandrosterone ratio was already higher before menarche in subjects who displayed early menarche during follow-up. These findings show that the increase in adrenal androgen secretion was mainly related to chronological age and was not affected by the time of menarche. The demonstration of early ovulation after early menarche is in conflict with the estrogen-window hypothesis suggesting a longer duration of anovulatory cycles to explain the increased risk of breast cancer after early menarche. Other theories should therefore be considered, among them the following: 1) high serum progesterone concentration in association with normal or high serum estradiol at puberty increases the risk, 2) only the early and relatively high estrogen concentrations are important, or 3) the estrogen to androgen ratio is the critical factor, with androgens having a protective effect.

Lower prevalence of breast cancer and cancers of the reproductive system among former college athletes compared to non-athletes

“…Pertinent to our results, a Age group (y) higher risk of cancer of the breast (Sherman et al, 1981;Miller & Bulbrook, 1980;Pike et al, 1981;3 Mean (±s.e. ) height, mean weight and DeWaard, 1981;Apter & Vihko, 1983), and cancer ted mean percent fat/body weight for athletes of the endometrium (Grodin et al, 1973;Forney et nd non-athletes ( x) by age group. al., 1981) are associated with early menarche, (Apter & Vihko, 1983) later menopause and greater relative fatness (Forney et al, 1981).…”

“…were on teams in secondary school or earlier, compared to only 24.9% of the non-athletes. Apter and Vihko (.1983) report that early maturers, (who were fatter than late maturers), had higher serum concentrations of oestradiol than the leaner, later maturing girls both before and after menarche, in relation to chronological age.…”

Detrimental psychological outcomes associated with early pubertal timing in adolescent girls

“…Medically, girls who experience early menarche prior to the age of twelve are more likely to test positive for the human papillomavirus (HPV), a sexually transmitted virus associated with increased risk for cervical cancer (Fisher, Rosenfeld, & Burk, 1991). Early maturers are also at a greater risk for teen pregnancy: the time from menarche until 50% of menstrual cycles are ovulatory is approximately 1 year if menarche occurs before age 12 but 4.5 years if menarche occurs at 13 or older (Apter & Vihko, 1983).…”

“…They also have higher levels of serum estradiol. Such hormonal differences persist well into adulthood, until girls reach their late 20s and early 30s (Apter & Vihko, 1983;Vihko & Apter, 1984;Apter, Reinila, & Vihko, 1989). …”

Isolation and the timing of mammary gland development, gonadarche, and ovarian senescence: Implications for mammary tumor burden

“…Epidemiological studies point convincingly to early puberty and delayed menopause as risk factors for breast cancer, arguing that it is the total estrogen exposure from puberty through menopause that creates risk (den Tonkelaar & de Waard, 1996;Moolgavkar et al, 1980;Petridou et al, 1996). Specifically, correlative epidemiological studies have identified the early onset of regular ovarian cycles after menarche as a risk factor (Apter & Vihko, 1983). Moreover, two different polymorphisms of the estrogen receptor a gene, which are associated with reduced breast cancer risk, were also associated with a relative delay in menarcheal age in Greek adolescent girls (Stavrou, Zois, Ioannidis, & Tsatsoulis, 2002).…”