Lifestyle factors associated with histologically derived human ovarian non-growing follicle count in reproductive age women.
OBJECTIVE
Are lifestyle factors (smoking, BMI, alcohol use and oral contraceptive pill use) associated with the human ovarian reserve as determined by the total ovarian non-growing follicle number?


CONCLUSIONS
Light to moderate alcohol use was significantly associated with greater ovarian non-growing follicle (NGF) count, whereas other lifestyle factors were not significantly related.


BACKGROUND
A single previous investigation has suggested that smoking and alcohol use are associated with lower ovarian follicle density. However, this investigation utilized follicle density as the outcome of interest rather than the estimated total ovarian NGF count.


METHODS
This cross-sectional investigation included a convenience sample of premenopausal women from two different academic sites, the University of Washington (n = 37, from 1999-2004) and the University of Oklahoma (n = 73, from 2004-2013), undergoing incidental oophorectomy at the time of hysterectomy (total n = 110, age range 21-52 years).


METHODS
Prior to undergoing oophorectomy, participants completed detailed questionnaires regarding lifestyle exposures. Following surgery, total ovarian NGF counts were determined with systematic random sampling rules and a validated fractionator/optical dissector technique. Associations between lifestyle factors and log-transformed ovarian follicle counts were determined using multivariable linear regression.


RESULTS
After controlling for age, BMI, oral contraceptive pill (OCP) use, tobacco use and site of collection, cumulative alcohol use (measured in alcoholic drinks per day multiplied by years of drinking) was associated with ovarian NGF count. Women reporting light (>0 to <1 drink-years) and moderate (1-3 drink-years) alcohol use had greater NGF counts (β = 0.75, P = 0.04, and β = 1.00, P = 0.03; light and moderate use, respectively) as compared with non-users. Neither heavier alcohol use (>3 drink-years), BMI, OCP use, nor tobacco use were significantly associated with the ovarian NGF count. Similar patterns of association with moderate cumulative alcohol use were observed when evaluating associations with pre-antral follicles and total follicle counts.


CONCLUSIONS
All participants in this convenience sample had a benign indication for hysterectomy, and therefore may not be broadly representative of the population without such an indication. Additionally, lifestyle factors were self-reported, and the sample size of the present investigation limits our ability to detect associations of smaller magnitude.


CONCLUSIONS
While our findings are in disagreement with a single investigation that utilized human follicle density as the outcome of interest, they are consistent with many studies investigating the relationship between lifestyle factors and the age of spontaneous menopause. Furthermore, they suggest a mechanism that does not involve accelerated follicular atresia to explain the association between smoking and an earlier age of menopause.


BACKGROUND
This investigation was funded by NIA R29-HD37360-04 (N.A.K.) and OCAST HR04-115 (K.R.H.) and by the National Institute of General Medical Sciences, Grant 1 U54GM104938 (J.D.P.). There is no conflict of interest.
Department of Biostatistics and Epidemiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
Jennifer D
JD
Peck
Department of Obstetrics and Gynecology, Section of Reproductive Endocrinology and Infertility, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
Alexander M
AM
Quaas
Department of Obstetrics and Gynecology, Section of Reproductive Endocrinology and Infertility, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
LaTasha B
LB
Craig
Seattle Reproductive Medicine, Seattle, WA, USA.
Michael R
MR
Soules
Seattle Reproductive Medicine, Seattle, WA, USA.
Nancy A
NA
Klein
Department of Obstetrics and Gynecology, Section of Reproductive Endocrinology and Infertility, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA karl-hansen@ouhsc.edu.
Karl R
KR
Hansen
D000328:Adult; D000428:Alcohol Drinking / Q000009:adverse effects; D003276:Contraceptives, Oral / Q000009:adverse effects; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D008019:Life Style; D008875:Middle Aged; D006080:Ovarian Follicle / Q000502:physiology*; D065851:Ovarian Reserve / Q000502:physiology*; D017697:Premenopause / Q000502:physiology*; D012907:Smoking / Q000009:adverse effects; D055815:Young Adult
D003276:Contraceptives, Oral
alcohol use; menopause; morphometric; non-growing follicles; oral contraceptive pill use; ovarian follicle count; ovarian reserve; primordial follicles; tobacco use