New Study Confirms Process Leading To Disorder Causing
Male Characteristics In Women
Ovarian
stimulation of male steroids is the culprit behind this disorder.
(June 22, 2004) - Bethesda, MD -- A woman finds
herself with excessive facial hair, obesity,
menstrual abnormalities, infertility, and enlarged ovaries may have
polycystic ovary syndrome (PCOS), an unfortunate
condition thought to be caused by excessive secretion by the ovaries of
androgen, a hormone associated with male characteristics. Men and
women both have hormones expressing male and female characteristics. Yet,
the cause of this excessive secretion of a hormone leading to undesired
gender traits remains unclear.
Estimates of incidence of this disorder range around
the five percent level if both cessation of ovulation and excess hair growth
are used in the definition, but they can range over 10 percent in some
select populations. Past research emphasized the relative roles of
neuroendocrine abnormalities leading to persistent and excessive secretion
of luteinizing hormones (LH), one of two
glycoprotein hormones that stimulate the final ripening of the follicles and
the secretion of progesterone; and the ovarian actions increased
insulin in plasma, a consequence of insulin resistance. Additional evidence
suggests that unnatural ovarian production of hormonal steroids is a primary
abnormality in PCOS.
Human studies of PCOS have found abnormal ovarian
steroid responses to administration of gonadial hormones, specifically
potent gonadotropin-releasing hormone (GnRH) agonist or a high dose of human
chorionic gonadotropin (hCG). The stimuli cause exaggerated secretion of
17-hydroxyprogesterone (17-OHP) and, to a lesser degree, androstenedione,
suggesting abnormal ovarian production of steroids. However, these
paradigms involve pharmacological ovarian stimulation and do not reproduce
physiological LH pulsatility.
Researchers recently hypothesized that
near-physiological LH stimuli would effect greater ovarian secretion of
androgens and their precursors in women with PCOS compared to controls. To
test this supposition, they employed a paradigm of sequential GnRH-receptor
antagonist administration to suppress endogenous LH concentrations, and
intermittent (pulse-like) infusions of physiological amounts of recombinant
human LH (rhLH) to stimulate ovarian steroidogenesis.
A New Study
The authors of “Exaggerated 17-Hydroxyprogesterone
Response to Intravenous Infusions of Recombinant Human LH in Women with
Polycystic Ovary Syndrome,” are Christopher R. McCartney, Amy B. Bellows,
Melissa B. Gingrich, Yun Hu, William S. Evans, John C. Marshall, and
Johannes D. Veldhuis, all from the University of Virginia Health System,
Charlottesville, VA. Their findings appear in the June, 2004, edition of the
American Journal of Physiology – Endocrinology and Metabolism. The
journal is one of 14 published each month by the American Physiological
Society (APS) (www.the-aps.org).
Methodology
This study sought to assess ovarian steroid secretion
in response to near-physiological gonadotropin stimuli in 12 ovulatory
controls and 7 women with PCOS. A gonadotropin-releasing hormone-receptor
antagonist (ganirelix, 2 mg subcutaneously) was given to block endogenous LH
secretion, followed by dexamethasone (0.75 mg orally) to suppress adrenal
androgen secretion. Twelve hours after ganirelix injection, intravenous
infusions of recombinant human LH were administered at four-hour intervals
with the highest dose last. Plasma LH, 17-hydroxyprogesterone (17-OHP),
androstenedione, and testosterone were measured concurrently. LH
dose-steroid response relationships (mean sex-steroid concentration versus.
mean LH concentration over four post-infusion) were examined for each
subject.
Results
The increased 17-OHP responses in PCOS observed in the
study may reflect exaggerated acute steroidogenic responses that parallel
escalating doses of rhLH. However, an alternative explanation is that the
17-OHP increase in PCOS reflects abrupt (in comparison to normal) rhLH-induced
resumption of early steroidogenic steps after temporary removal of
physiological LH stimulation.
The findings revealed that leuteinizing hormone
dose-ovarian steroid responses were not observed in normal women.
Furthermore, acute ovarian steroid responses to rhLH infusions were not
commonly apparent when reviewing individual steroid time series. It remains
possible that ovarian steroid responses could have occurred after our
surveillance had ended. Nonetheless, the observations suggest that ovarian
steroidogenesis during the normal follicular phase is influenced by
integrated LH stimulation and does not vary acutely to changes in LH pulse
mass. This contrasts with acute P responses to endogenous LH pulses during
the luteal phase.
Conclusions
The authors conclude that that near-physiological
ovarian stimulation via intermittent (pulse-like) rhLH administration
produces exaggerated 17-hydroxyprogesterone secretion in patients with PCOS,
supporting earlier studies of pharmacological ovarian stimulation. The next
step in the key to prevention is to determine the physiological mechanisms
leading to this disorder.
- end -
Source: June, 2004 edition of the American Journal
of Physiology – Endocrinology and Metabolism. The journal is one of 14
published each month by the American Physiological Society (APS) (www.the-aps.org).
The
American Physiological Society (APS) was founded in 1887 to foster basic and
applied science, much of it relating to human health. The Bethesda, MD-based
Society has more than 10,000 members and publishes 3,800 articles in its 14
peer-reviewed journals every year.
***
Editor’s Note: A copy of the research article is
available in pdf format to the press. Members of the press are invited to
obtain a pdf copy of the study and to interview members of the research
team. To do so, please contact Donna Krupa at 703.527.7357 (direct dial),
703.967.2751 (cell) or djkrupa1@aol.com.
